Identification

Name
Olaparib
Accession Number
DB09074  (DB05940)
Type
Small Molecule
Groups
Approved
Description

Olaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2, and PARP3. PARP enzymes are involved in normal cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNA repair. Olaparib has been shown to inhibit growth of select tumor cell lines in vitro and decrease tumor growth in mouse xenograft models of human cancer both as monotherapy or following platinum-based chemotherapy. Increased cytotoxicity and anti-tumor activity following treatment with olaparib were noted in cell lines and mouse tumor models with deficiencies in BRCA. In vitro studies have shown that olaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complex, resulting in disruption of cellular homeostasis and cell death.

Olaparib is available as oral tablets marketed under the brand name Lynparza and was initially indicated as a maintenance therapy or monotherapy for the treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer. On January 12, 2018, FDA expanded the approved use of Lynparza to include chemotherapy-experienced patients with germline breast cancer susceptibility gene (BRCA) mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. In a randomized clinical trial involving patients with HER2-negative metastatic breast cancer with a germline BRCA mutation, the median progression-free survival for patients taking Lynparza was 7 months compared to 4.2 months for patients taking chemotherapy only. Patient selection for this newly-approved indication can be performed based on an FDA-approved genetic test, called the BRACAnalysis CDx.

Moreover, in December of 2018 the FDA further approved the categorization and use of Lynparza (olaparib) as frontline maintenance therapy in ovarian cancer, making the medication the first time a PARP inhibitor has been approved in the first-line maintenance setting 7. This new approval for frontline maintenance now allows patients who have had surgery and complete or partial response to platinum-based therapy after being first diagnosed with the cancer to be treated with olaparib to decrease the risk of recurrence or delay it significantly 7. This approval is based on findings from the phase 3 SOLO-1 trial for olaparib, which demonstrated the capacity for the agent to reduce the risk of disease progression or death by 70% in patients with BRCA-mutant advanced ovarian cancer who were in complete or partial response to platinum-based chemotherapy 7. It is expected that the ability to offer this important first-line maintenance treatment option to eligible patients may slow down or even stop the natural course of disease progression 7.

Structure
Thumb
Synonyms
  • 4-(3-{[4-(cyclopropylcarbonyl)piperazin-1-yl]carbonyl}-4-fluorobenzyl)phthalazin-1(2H)-one
  • Olaparib
External IDs
AZD 2281 / AZD-2281 / AZD2281 / KU-0059436 / KU-59436 / KU59436
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LynparzaCapsule50 mgOralAstra Zeneca2016-05-16Not applicableCanada
LynparzaTablet, film coated150 mg/1OralAstraZeneca Pharmaceuticals LP2017-08-17Not applicableUs
LynparzaTablet, film coated100 mg/1OralAstraZeneca Pharmaceuticals LP2017-08-17Not applicableUs
LynparzaCapsule50 mg/1OralAstraZeneca Pharmaceuticals LP2014-12-242020-03-31Us
LynparzaTablet150 mgOralAstra Zeneca2018-05-23Not applicableCanada
LynparzaTablet100 mgOralAstra Zeneca2018-05-23Not applicableCanada
Additional Data Available
  • Application Number
    Application Number

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  • Product Code
    Product Code

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Categories
UNII
WOH1JD9AR8
CAS number
763113-22-0
Weight
Average: 434.4628
Monoisotopic: 434.175418827
Chemical Formula
C24H23FN4O3
InChI Key
FDLYAMZZIXQODN-UHFFFAOYSA-N
InChI
InChI=1S/C24H23FN4O3/c25-20-8-5-15(14-21-17-3-1-2-4-18(17)22(30)27-26-21)13-19(20)24(32)29-11-9-28(10-12-29)23(31)16-6-7-16/h1-5,8,13,16H,6-7,9-12,14H2,(H,27,30)
IUPAC Name
4-{[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorophenyl]methyl}-1,2-dihydrophthalazin-1-one
SMILES
FC1=CC=C(CC2=NNC(=O)C3=CC=CC=C23)C=C1C(=O)N1CCN(CC1)C(=O)C1CC1

Pharmacology

Indication

Olaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for the treatment of:

(I) Ovarian cancer, in which the medication is intended for [a] the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy, or [b] for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy Label. Select patients for therapy based on an FDA-approved companion diagnostic for olaparib Label.

[II] Breast cancer, in which the medication is intended for use in patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have previously been treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine treatment Label. Select patients for therapy based on an FDA-approved companion diagnostic for olaparib Label.

Associated Conditions
Pharmacodynamics

The effect of olaparib on cardiac repolarization was assessed in 119 patients following a single dose of 300 mg and in 109 patients following multiple dosing of 300 mg twice daily Label. No clinically relevant effect of olaparib on QT interval was observed Label.

Mechanism of action

Olaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2, and PARP3. PARP enzymes are involved in normal cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNA repair Label. Olaparib has been shown to inhibit growth of select tumor cell lines in vitro and decrease tumor growth in mouse xenograft models of human cancer both as monotherapy or following platinum-based chemotherapy Label. Increased cytotoxicity and anti-tumor activity following treatment with olaparib were noted in cell lines and mouse tumor models with deficiencies in BRCA Label. In vitro studies have shown that olaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complex, resulting in disruption of cellular homeostasis and cell death Label.

TargetActionsOrganism
APoly [ADP-ribose] polymerase 1
inhibitor
Humans
APoly [ADP-ribose] polymerase 2
inhibitor
Humans
APoly [ADP-ribose] polymerase 3
inhibitor
Humans
Additional Data Available
Adverse Effects

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Contraindications

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Blackbox Warnings

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Absorption

Following oral administration, the absorption of olaparib is very rapid and can reach a peak concentration ranging between 4.7 and 9.1 mcg/ml after 1-3 hours. The reported AUC of olaparib after a dose of 200 mg is of 25.8 mcg.h/L and this AUC can be increased by 26% with constant administration. The consumption of a high-fat diet with olaparib can only decrease the tmax but do not have an effect in the peak concentration.6

Volume of distribution

After administration of a dose of 100 mg/kg, the reported volume of distribution was of 40.3 L.6

Protein binding

In vitro studies have reported that the plasma protein binding of olaparib was reported to be of 82%.5

Metabolism

Olaparib is extensively metabolized in the liver by the action of CYP3A isoenzymes.9 From the administered dose, the unchanged form of olaparib accounted for 70% of the circulating dose and it was considered the major component in urine and feces.8

The metabolic pathway of olaparib is mainly attributable to oxidation reactions with subsequent glucuronide and sulfate conjugation. However, the over 20 metabolites found in plasma, urine, and feces represented a minor portion of the administered dose. The major circulating metabolites were represented by the mono-oxygenated form and the piperazin-3-ol form.8

Route of elimination

From the administered dose, approximately 86% of the administered dose is recovered after 7 days from which 44% is found in the urine and 42% is obtained in feces.8

Half life

The reported elimination half-life ranges between 5 to 11 hours.6

Clearance

The total clearance of olaparib was reported to be 4.6 L/h.6

Toxicity

The most commonly reported side effects reported during clinical trials included cough, constipation, dysgeusia, peripheral deem, back pain, dizziness, headache, urinary tract infection, dyspnea, and rash Label 8,9. Myelodysplastic syndrome/Acute Myeloid Leukemia (MDS/AML) was reported in 2% of patients with deleterious or suspected deleterious germline BRCA-mutated advanced cancers Label 8,9. The majority of cases were fatal and the duration of therapy with olaparib in patients who developed secondary cancers varied from <6 months to >2 years Label 8,9. Complete blood count should be tested at baseline and monthly following therapy initiation to monitor for MDS/AML Label 8,9. Pneumonitis, including fatal cases, occurred in <1% of patients treated with olaparib Label 8,9. Patients should be monitored for new or worsening respiratory symptoms such as dyspnea, fever, cough, or wheezing Label 8,9. Olaparib was found to be teratogenic and causes embryo-fetal toxicity in rats Label 8,9. It should, therefore, be avoided during pregnancy and its use should be combined with effective contraception during treatment Label 8,9.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinThe serum concentration of (R)-warfarin can be increased when it is combined with Olaparib.
(S)-WarfarinThe serum concentration of (S)-Warfarin can be increased when it is combined with Olaparib.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when 2-Methoxyethanol is combined with Olaparib.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Olaparib.
9-(N-methyl-L-isoleucine)-cyclosporin AThe risk or severity of adverse effects can be increased when Olaparib is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be decreased when combined with Olaparib.
AbataceptThe metabolism of Olaparib can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Olaparib.
AbemaciclibOlaparib may decrease the excretion rate of Abemaciclib which could result in a higher serum level.
AbetimusThe risk or severity of adverse effects can be increased when Abetimus is combined with Olaparib.
Additional Data Available
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  • Severity
    Severity

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Food Interactions
  • Avoid grapefruit products. Grapefruit inhibits the CYP3A metabolism of olaparib, which may increase its serum concentration.
  • Avoid St. John's Wort. This herb induces the CYP3A metabolism of olaparib and may reduce its serum concentration.
  • Take with or without food.

References

Synthesis Reference

Menear KA, Adcock C, Boulter R, Cockcroft XL, Copsey L, Cranston A, Dillon KJ, Drzewiecki J, Garman S, Gomez S, Javaid H, Kerrigan F, Knights C, Lau A, Loh VM Jr, Matthews IT, Moore S, O'Connor MJ, Smith GC, Martin NM: 4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin- 1-one: a novel bioavailable inhibitor of poly(ADP-ribose) polymerase-1. J Med Chem. 2008 Oct 23;51(20):6581-91. doi: 10.1021/jm8001263. Epub 2008 Sep 19. Pubmed

General References
  1. Frampton JE: Olaparib: a review of its use as maintenance therapy in patients with ovarian cancer. BioDrugs. 2015 Apr;29(2):143-50. doi: 10.1007/s40259-015-0125-6. [PubMed:25899311]
  2. Menear KA, Adcock C, Boulter R, Cockcroft XL, Copsey L, Cranston A, Dillon KJ, Drzewiecki J, Garman S, Gomez S, Javaid H, Kerrigan F, Knights C, Lau A, Loh VM Jr, Matthews IT, Moore S, O'Connor MJ, Smith GC, Martin NM: 4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin- 1-one: a novel bioavailable inhibitor of poly(ADP-ribose) polymerase-1. J Med Chem. 2008 Oct 23;51(20):6581-91. doi: 10.1021/jm8001263. Epub 2008 Sep 19. [PubMed:18800822]
  3. Hay T, Matthews JR, Pietzka L, Lau A, Cranston A, Nygren AO, Douglas-Jones A, Smith GC, Martin NM, O'Connor M, Clarke AR: Poly(ADP-ribose) polymerase-1 inhibitor treatment regresses autochthonous Brca2/p53-mutant mammary tumors in vivo and delays tumor relapse in combination with carboplatin. Cancer Res. 2009 May 1;69(9):3850-5. doi: 10.1158/0008-5472.CAN-08-2388. Epub 2009 Apr 21. [PubMed:19383921]
  4. Rottenberg S, Jaspers JE, Kersbergen A, van der Burg E, Nygren AO, Zander SA, Derksen PW, de Bruin M, Zevenhoven J, Lau A, Boulter R, Cranston A, O'Connor MJ, Martin NM, Borst P, Jonkers J: High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs. Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):17079-84. doi: 10.1073/pnas.0806092105. Epub 2008 Oct 29. [PubMed:18971340]
  5. Irwin CP, Portorreal Y, Brand C, Zhang Y, Desai P, Salinas B, Weber WA, Reiner T: PARPi-FL--a fluorescent PARP1 inhibitor for glioblastoma imaging. Neoplasia. 2014 May;16(5):432-40. doi: 10.1016/j.neo.2014.05.005. Epub 2014 Jun 23. [PubMed:24970386]
  6. Solimando DA Jr, Waddell JA: Nivolumab and Olaparib. Hosp Pharm. 2015 May;50(5):356-66. doi: 10.1310/hpj5005-356. [PubMed:26405320]
  7. FDA Approves Olaparib as Frontline Maintenance Therapy in Ovarian Cancer Press Release [Link]
  8. Olaparib New Zealand Data Sheet [Link]
  9. Linparza (olaparib) drug monograph [File]
External Links
KEGG Drug
D09730
ChemSpider
23343272
BindingDB
27566
RxNav
1597582
ChEBI
83766
ChEMBL
CHEMBL521686
ZINC
ZINC000040430143
PDBe Ligand
09L
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Olaparib
ATC Codes
L01XX46 — Olaparib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
3u9y / 4tkg / 4tvj / 5ds3
FDA label
Download (481 KB)
MSDS
Download (109 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Active Not RecruitingTreatmentOvarian Cancer1
0RecruitingBasic ScienceBreast Cancer / Ovarian Cancer1
0RecruitingBasic ScienceOvarian Cancer1
0RecruitingTreatmentBRCA-Mutated Ovarian Carcinoma / BRCA1 Gene Mutation / Brca2 Gene Mutation / High Grade Fallopian Tube Serous Adenocarcinoma / High Grade Ovarian Serous Adenocarcinoma / Primary Peritoneal High Grade Serous Adenocarcinoma / Stage III Fallopian Tube Cancer AJCC v8 / Stage III Ovarian Cancer AJCC v8 / Stage III Primary Peritoneal Cancer AJCC v8 / Stage IIIA Fallopian Tube Cancer AJCC v8 / Stage IIIA Ovarian Cancer AJCC v8 / Stage IIIA Primary Peritoneal Cancer AJCC v8 / Stage IIIA1 Fallopian Tube Cancer AJCC v8 / Stage IIIA1 Ovarian Cancer AJCC v8 / Stage IIIA2 Fallopian Tube Cancer AJCC v8 / Stage IIIA2 Ovarian Cancer AJCC v8 / Stage IIIB Fallopian Tube Cancer AJCC v8 / Stage IIIB Ovarian Cancer AJCC v8 / Stage IIIB Primary Peritoneal Cancer AJCC v8 / Stage IIIC Fallopian Tube Cancer AJCC v8 / Stage IIIC Ovarian Cancer AJCC v8 / Stage IIIC Primary Peritoneal Cancer AJCC v8 / Stage IV Fallopian Tube Cancer AJCC v8 / Stage IV Ovarian Cancer AJCC v8 / Stage IV Primary Peritoneal Cancer AJCC v8 / Stage IVA Fallopian Tube Cancer AJCC v8 / Stage IVA Ovarian Cancer AJCC v8 / Stage IVA Primary Peritoneal Cancer AJCC v8 / Stage IVB Fallopian Tube Cancer AJCC v8 / Stage IVB Ovarian Cancer AJCC v8 / Stage IVB Primary Peritoneal Cancer AJCC v81
0RecruitingTreatmentBorderline Resectable Pancreatic Adenocarcinoma / Locally Advanced Pancreatic Ductal Adenocarcinoma / Metastatic Pancreatic Ductal Adenocarcinoma / Resectable Pancreatic Ductal Adenocarcinoma / Stage I Pancreatic Cancer AJCC v8 / Stage IA Pancreatic Cancer AJCC v8 / Stage IB Pancreatic Cancer AJCC v8 / Stage II Pancreatic Cancer AJCC v8 / Stage IIA Pancreatic Cancer AJCC v8 / Stage IIB Pancreatic Cancer AJCC v8 / Stage III Pancreatic Cancer AJCC v8 / Stage IV Pancreatic Cancer AJCC v81
0RecruitingTreatmentPulmonary Arterial Hypertension (PAH)1
1Active Not RecruitingBasic ScienceTumors, Solid1
1Active Not RecruitingOtherTumors, Solid2
1Active Not RecruitingTreatmentAdvanced Ovarian Cancer / Carboplatin / Paclitaxel / Triple Negative Metastatic Breast Cancer1
1Active Not RecruitingTreatmentAdvanced Solid Tumors1
1Active Not RecruitingTreatmentAdvanced Solid Tumours1
1Active Not RecruitingTreatmentAnatomic Stage IV Breast Cancer AJCC v8 / Estrogen Receptor Negative / HER2/Neu Negative / Progesterone Receptor Negative / Prognostic Stage IV Breast Cancer AJCC v8 / Triple-Negative Breast Carcinoma1
1Active Not RecruitingTreatmentBRCA1 Protein / BRCA2 Protein / Neoplasms, Ovarian1
1Active Not RecruitingTreatmentBone Tumors / Soft Tissue Sarcoma (STS)1
1Active Not RecruitingTreatmentBreast Cancer / Ovarian Cancer1
1Active Not RecruitingTreatmentBreast Neoplasm Malignant Female / Breast Neoplasms, Triple-Negative / Radiotherapy Side Effect1
1Active Not RecruitingTreatmentFallopian Tube Cancer / Ovarian Cancer / Primary Peritoneal Cancer1
1Active Not RecruitingTreatmentHead and Neck Carcinoma1
1Active Not RecruitingTreatmentHead and Neck Squamous Cell Carcinoma (HNSCC)1
1Active Not RecruitingTreatmentInflammatory Breast Carcinoma / Locally Advanced Malignant Neoplasm / Triple-Negative Invasive Breast Carcinoma1
1Active Not RecruitingTreatmentLaryngeal Cancer Stage II / Laryngeal Cancer Stage III / Neoplasms, Head and Neck / Squamous Cell Carcinoma (SCC)1
1Active Not RecruitingTreatmentMalignant Solid Tumours1
1Active Not RecruitingTreatmentMetastatic Fallopian Tube Serous Adenocarcinoma / Metastatic Malignant Solid Neoplasm / Metastatic Primary Peritoneal Serous Adenocarcinoma / Metastatic Triple-Negative Breast Carcinoma / Platinum-Resistant Fallopian Tube Carcinoma / Platinum-Resistant Ovarian Carcinoma / Platinum-Resistant Primary Peritoneal Carcinoma / Recurrent Breast Carcinoma / Recurrent High Grade Fallopian Tube Serous Adenocarcinoma / Recurrent High Grade Ovarian Serous Adenocarcinoma / Recurrent Primary Peritoneal High Grade Serous Adenocarcinoma / Recurrent Triple-Negative Breast Carcinoma / Refractory Fallopian Tube Serous Adenocarcinoma / Refractory Ovarian Serous Adenocarcinoma / Refractory Primary Peritoneal Serous Adenocarcinoma / Refractory Triple-Negative Breast Carcinoma / Unresectable Fallopian Tube Serous Adenocarcinoma / Unresectable Malignant Solid Neoplasm / Unresectable Primary Peritoneal Serous Adenocarcinoma1
1Active Not RecruitingTreatmentMuscle Invasive Bladder Cancer1
1Active Not RecruitingTreatmentTumors, Solid2
1CompletedNot AvailableTumors, Solid3
1CompletedBasic ScienceTumors, Solid1
1CompletedOtherProstate Cancer1
1CompletedOtherTumors, Solid1
1CompletedTreatmentAdvanced Solid Malignancies1
1CompletedTreatmentAdvanced Solid Malignancies / Malignancies1
1CompletedTreatmentAdvanced Solid Tumours1
1CompletedTreatmentBrain and Central Nervous System Tumors1
1CompletedTreatmentBreast Cancer / Cancer, Advanced / Ovarian Cancer1
1CompletedTreatmentBreast Cancer / Cervical Cancers / Endometrial Cancer / Fallopian Tube Cancer / Ovarian Cancer / Primary Peritoneal Cancer1
1CompletedTreatmentBreast Cancer / Metastatic Breast Cancer / Triple Negative Breast Cancer (TNBC)1
1CompletedTreatmentCancer, Advanced1
1CompletedTreatmentColorectal Cancers1
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1CompletedTreatmentMalignant Neoplasm of Pancreas1
1CompletedTreatmentMalignant Solid Tumours1
1CompletedTreatmentMelanoma Neoplasms1
1CompletedTreatmentNeoplasms1
1CompletedTreatmentNeoplasms Metastasis2
1CompletedTreatmentNeoplasms, Pancreatic1
1CompletedTreatmentOvarian, Breast, and Second-Line Small Cell Lung Cancer / Refractory Solid Tumours / Relapsed Small Cell Lung Cancer (SCLC)1
1CompletedTreatmentSquamous Cell Carcinoma of the Head and Neck (SCCHN)1
1Not Yet RecruitingTreatmentAdvanced Breast Cancer / BRCA1 Mutations / BRCA2 Mutation / Locally Advanced Breast Cancer (LABC) / Metastatic Breast Cancer1
1Not Yet RecruitingTreatmentBreast Cancer / Metastatic Breast Cancer1
1RecruitingTreatmentAdvanced Malignant Neoplasm / Recurrent Malignant Neoplasm / Refractory Malignant Neoplasm1
1RecruitingTreatmentAdvanced Malignant Solid Neoplasm / Metastatic Malignant Solid Neoplasm / Refractory Malignant Solid Neoplasm / Unresectable Malignant Solid Neoplasm1
1RecruitingTreatmentAdvanced Malignant Solid Neoplasm / Metastatic Malignant Solid Neoplasm / Unresectable Malignant Solid Neoplasm1
1RecruitingTreatmentBreast Cancer / Leukemia Acute Myeloid Leukemia (AML) / Malignant Neoplasm of Pancreas / Prostate Cancer1
1RecruitingTreatmentBreast Cancer / Malignant Lymphomas / Malignant Neoplasm of Pancreas / Malignant Solid Tumours / Ovarian Cancer / Prostate Cancer1
1RecruitingTreatmentCarcinoma of the Oesophagus1
1RecruitingTreatmentAdvanced thymic carcinoma / Clinical Trial, Phase I / Mesothelioma / Neuroendocrine Tumors1
1RecruitingTreatmentEwing's Sarcoma (ES) / Rhabdomyosarcomas1
1RecruitingTreatmentMalignant Neoplasm of Breast / Malignant Neoplasms of Digestive Organs / Malignant Neoplasms of Female Genital Organs / Malignant Neoplasms of Male Genital Organs / Malignant Neoplasms of Thyroid and Other Endocrine Glands1
1RecruitingTreatmentMetastatic Castration Resistant Prostate Cancer1
1RecruitingTreatmentMetastatic Castration Resistant Prostate Cancer (mCRPC)1
1RecruitingTreatmentMetastatic Malignant Neoplasm in the Chest Wall / Metastatic Melanoma / Recurrent Breast Carcinoma1
1RecruitingTreatmentRecurrent Diffuse Large B-Cell Lymphoma / Recurrent T-Cell Non-Hodgkin Lymphoma / Refractory Diffuse Large B Cell Lymphoma / Refractory Hodgkin Lymphoma / Refractory T-Cell Non-Hodgkin Lymphoma1
1RecruitingTreatmentSmall Cell Lung Cancer (SCLC)1
1RecruitingTreatmentSmall Cell Lung Cancer (SCLC) / Small Cell Lung Cancer Extensive Stage1
1RecruitingTreatmentSoft Tissue Sarcoma (STS) / Soft-Tissue Sarcoma1
1RecruitingTreatmentSolid Tumor, Adult1
1RecruitingTreatmentTumors, Solid1
1TerminatedTreatmentBreast Cancer1
1WithdrawnTreatmentMalignant Lymphomas1
1WithdrawnTreatmentSquamous Cell Carcinoma (SCC)1
1WithdrawnTreatmentSquamous Cell Carcinoma of the Head and Neck (SCCHN)1
1, 2Active Not RecruitingTreatmentBreast / Malignant Neoplasm of Stomach / Ovarian / Small Cell Lung Cancer (SCLC)1
1, 2Active Not RecruitingTreatmentDeleterious BRCA1 Gene Mutation / Deleterious BRCA2 Gene Mutation / Estrogen Receptor Negative / HER2/Neu Negative / Ovarian Endometrioid Adenocarcinoma / Ovarian Serous Adenocarcinoma / Ovarian Serous Cystadenocarcinoma / Ovarian Serous Surface Papillary Adenocarcinoma / Progesterone Receptor Negative / Recurrent Breast Carcinoma / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma / Triple-Negative Breast Carcinoma1
1, 2Active Not RecruitingTreatmentBrca1 Mutation Carrier / Brca2 Mutation Carrier / Endometrial Adenocarcinomas / Estrogen Receptor Negative / HER2/Neu Negative / High Grade Ovarian Serous Adenocarcinoma / Progesterone Receptor Negative / Recurrent Breast Carcinoma / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma / Recurrent Uterine Corpus Carcinoma / Stage III Uterine Corpus Cancer AJCC v7 / Stage IV Breast Cancer AJCC v6 and v7 / Stage IV Uterine Corpus Cancer AJCC v7 / Triple-Negative Breast Carcinoma1
1, 2Active Not RecruitingTreatmentPrimary Peritoneal Carcinoma1
1, 2Active Not RecruitingTreatmentRecurrent Endometrial Cancer1
1, 2Active Not RecruitingTreatmentStage III Ovarian Cancer / Stage IV Ovarian Cancer / Uterine Malignancies1
1, 2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2Not Yet RecruitingTreatmentGastroenteropancreatico Tumors / Neuroendocrine Neoplasms / Neuroendocrine Tumors1
1, 2RecruitingDiagnosticOral Squamous Cell Carcinoma (OSCC)1
1, 2RecruitingTreatmentAbdominal wall neoplasm / Fallopian Tube Cancer / Ovarian Cancer1
1, 2RecruitingTreatmentAdv Solid Malig - H&N SCC, ATM Pro / Def NSCLC, Gastric, Breast and Ovarian Cancer1
1, 2RecruitingTreatmentAdvanced Malignancies1
1, 2RecruitingTreatmentAdvanced Solid Tumors / Breast Cancer / Cancer, Advanced / Endometrial Cancer / Ovarian Cancer1
1, 2RecruitingTreatmentBreast Cancer1
1, 2RecruitingTreatmentCastration-Resistant Prostate Carcinoma / Metastatic Prostate Adenocarcinoma1
1, 2RecruitingTreatmentChildren, Adolescents and Young Adults With Refractory or Recurrent Malignancies1
1, 2RecruitingTreatmentFallopian Tube Cancer / Fallopian Tube Carcinosarcoma / Fallopian Tube Clear Cell Adenocarcinoma / Fallopian Tube Endometrioid Adenocarcinoma / High Grade Fallopian Tube Serous Adenocarcinoma / High Grade Ovarian Serous Adenocarcinoma / Ovarian Carcinosarcoma / Ovarian Clear Cell Adenocarcinoma / Ovarian Endometrioid Adenocarcinoma / Primary Peritoneal Serous Adenocarcinoma / Recurrent Endometrial Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma1
1, 2RecruitingTreatmentGliomas, Malignant / PARP Inhibitor / Radiotherapy1
1, 2RecruitingTreatmentMetastatic Esophageal Carcinoma / Metastatic Gastric carcinoma / Metastatic Gastroesophageal Junction Adenocarcinoma / Recurrent Esophageal Carcinoma / Recurrent Gastric Carcinoma / Recurrent Gastroesophageal Junction Adenocarcinoma / Stage III Esophageal Cancer AJCC v7 / Stage III Gastric Cancer AJCC v7 / Stage IIIA Esophageal Cancer AJCC v7 / Stage IIIA Gastric Cancer AJCC v7 / Stage IIIB Esophageal Cancer AJCC v7 / Stage IIIB Gastric Cancer AJCC v7 / Stage IIIC Esophageal Cancer AJCC v7 / Stage IIIC Gastric Cancer AJCC v7 / Stage IV Esophageal Cancer AJCC v7 / Stage IV Gastric Cancer AJCC v7 / Unresectable Esophageal Carcinoma / Unresectable Gastric Carcinoma / Unresectable Gastroesophageal Junction Adenocarcinoma1
1, 2RecruitingTreatmentNeoplasms, Breast1
1, 2RecruitingTreatmentNeoplasms, Breast / Neoplasms, Colorectal1
1, 2RecruitingTreatmentNeoplasms, Lung / Prostate Cancer / Small Cell Lung Cancer (SCLC) / Transitional Cell Carcinoma / Urothelial Cancer1
1, 2RecruitingTreatmentPulmonary Arterial Hypertension (PAH)1
1, 2RecruitingTreatmentSmall Cell Lung Cancer (SCLC)1
2Active Not RecruitingBasic ScienceBreast Cancer1
2Active Not RecruitingTreatmentATM Gene Mutation / BRIP1 Gene Mutation / CHEK2 Gene Mutation / Invasive Breast Cancer / Metastatic Breast Cancer / NBN Gene Mutation / PALB2 Gene Mutation / RAD51 Gene Mutation / Somatic Mutation Breast Cancer (BRCA1) / Somatic Mutation Breast Cancer (BRCA2)1
2Active Not RecruitingTreatmentAdenocarcinoma of the Prostate1
2Active Not RecruitingTreatmentAdvanced Ovarian Cancer1
2Active Not RecruitingTreatmentAdvanced Tumours / Breast / Ovarian / Pancreatic / Prostate1
2Active Not RecruitingTreatmentBreast Cancer / Ovarian Carcinoma1
2Active Not RecruitingTreatmentBreast Cancer / Triple Negative Breast Cancer (TNBC)1
2Active Not RecruitingTreatmentCastration-Resistant Prostate Carcinoma / Metastatic Hormone Refractory Prostate Cancer / Prostate Adenocarcinoma With Neuroendocrine Differentiation / Prostate Carcinoma Metastatic in the Bone / Prostate Small Cell Carcinoma / Stage IV Prostate Adenocarcinoma AJCC v71
2Active Not RecruitingTreatmentFallopian Tube Endometrioid Adenocarcinoma / Fallopian Tube Serous Adenocarcinoma / High Grade Ovarian Serous Adenocarcinoma / Ovarian Endometrioid Tumor / Primary Peritoneal Serous Adenocarcinoma / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma1
2Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Non-small Cell Lung Cancer NSCLC1
2Active Not RecruitingTreatmentMalignancies1
2Active Not RecruitingTreatmentMalignant Neoplasm of Stomach1
2Active Not RecruitingTreatmentMetastatic Breast Cancer1
2Active Not RecruitingTreatmentMetastatic Castration Resistant Prostate Cancer1
2Active Not RecruitingTreatmentMetastatic Non-Small Cell Lung Cancer1
2Active Not RecruitingTreatmentMutant High Grade Glioma / Recurrent IDH / Recurrent IDH-mutant High Grade Glioma1
2Active Not RecruitingTreatmentNeoplasms, Breast1
2Active Not RecruitingTreatmentNeoplasms, Germ Cell and Embryonal1
2Active Not RecruitingTreatmentNeoplasms, Ovarian1
2Active Not RecruitingTreatmentOvarian Cancer4
2Active Not RecruitingTreatmentOvarian Epithelial Cancer / Relapses1
2Active Not RecruitingTreatmentPancreatic Adenocarcinoma Metastatic / Pancreatic Ductal Adenocarcinoma / Stage IV Pancreatic Cancer AJCC v6 and v71
2Active Not RecruitingTreatmentPlatinum Refractory Extensive-Stage Small Cell Lung Carcinoma1
2Active Not RecruitingTreatmentRecurrent Glioblastoma1
2Active Not RecruitingTreatmentRecurrent Platinum Resistant Ovarian Cancer1
2Active Not RecruitingTreatmentRelapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity1
2Active Not RecruitingTreatmentSmall Cell Lung Cancer (SCLC)1
2Active Not RecruitingTreatmentUrinary Bladder Neoplasms1
2CompletedTreatmentBRCA 1 /2 and / or HRD / Breast Cancer / HRpos Breast Neoplasms / Triple Negative Breast Neoplasms1
2CompletedTreatmentCancer, Bladder1
2CompletedTreatmentColorectal Cancers1
2CompletedTreatmentEwing's Sarcoma (ES)1
2CompletedTreatmentNeoplasms, Ovarian2
2CompletedTreatmentOvarian Cancer1
2CompletedTreatmentSquamous Cell Carcinoma of the Head and Neck (SCCHN)1
2Not Yet RecruitingBasic ScienceRenal Cell Adenocarcinoma1
2Not Yet RecruitingTreatmentARID1A Gene Mutation / ATM Gene Mutation / ATR Gene Mutation / Bile duct adenocarcinoma / BRCA1 Gene Mutation / Brca2 Gene Mutation / BRIP1 Gene Mutation / CHEK2 Gene Mutation / EMSY Gene Mutation / Fanconi Anemia Complementation Group Gene Mutation / Metastatic Bile Duct Carcinoma / MRE11 Gene Mutation / NBN Gene Mutation / PALB2 Gene Mutation / PTEN Gene Deletion / RAD51 Gene Mutation1
2Not Yet RecruitingTreatmentAcute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome / Acute, recurrent Myeloid Leukemia / IDH1 NP_005887.2:p.R132C / IDH1 NP_005887.2:p.R132G / IDH1 NP_005887.2:p.R132H / IDH1 NP_005887.2:p.R132L / IDH1 NP_005887.2:p.R132S / IDH1 NP_005887.2:p.R132V / IDH2 NP_002159.2:p.R140L / IDH2 NP_002159.2:p.R140Q / IDH2 NP_002159.2:p.R140W / IDH2 NP_002159.2:p.R140X / IDH2 NP_002159.2:p.R172G / IDH2 NP_002159.2:p.R172K / IDH2 NP_002159.2:p.R172M / IDH2 NP_002159.2:p.R172S / IDH2 NP_002159.2:p.R172W / Myelodysplastic Syndrome / Refractory Acute Myelogenous Leukemia (AML) / Therapy-Related Acute Myeloid Leukemia1
2Not Yet RecruitingTreatmentAdenocarcinoma of the Prostate / Prostate Cancer1
2Not Yet RecruitingTreatmentAdenocarcinoma, Prostate / Biochemically Recurrent Prostate Carcinoma1
2Not Yet RecruitingTreatmentAdvanced Adrenal Gland Pheochromocytoma / Advanced Paraganglioma / Metastatic Adrenal Gland Pheochromocytoma / Metastatic Paraganglioma / Unresectable Adrenal Gland Pheochromocytoma / Unresectable Paraganglioma1
2Not Yet RecruitingTreatmentAdvanced Breast Carcinoma / Anatomic Stage III Breast Cancer AJCC v8 / Anatomic Stage IIIA Breast Cancer AJCC v8 / Anatomic Stage IIIB Breast Cancer AJCC v8 / Anatomic Stage IIIC Breast Cancer AJCC v8 / Anatomic Stage IV Breast Cancer AJCC v8 / Germline BRCA1 Gene Mutation / Germline BRCA2 Gene Mutation / HER2/Neu Negative / Metastatic Breast Carcinoma / Prognostic Stage III Breast Cancer AJCC v8 / Prognostic Stage IIIA Breast Cancer AJCC v8 / Prognostic Stage IIIB Breast Cancer AJCC v8 / Prognostic Stage IIIC Breast Cancer AJCC v8 / Prognostic Stage IV Breast Cancer AJCC v81
2Not Yet RecruitingTreatmentAdvanced Gastric Adenocarcinoma1
2Not Yet RecruitingTreatmentAdvanced Soft Tissue Sarcoma1
2Not Yet RecruitingTreatmentBile Duct Carcinoma / Chemotherapy Effect1
2Not Yet RecruitingTreatmentCancers With DNA Repair-Deficiency1
2Not Yet RecruitingTreatmentCholangiocarcinomas / Gliomas / IDH Mutation / Tumors, Solid1
2Not Yet RecruitingTreatmentEndometrial Carcinoma1
2Not Yet RecruitingTreatmentImmunotherapy1
2Not Yet RecruitingTreatmentMelanoma1
2Not Yet RecruitingTreatmentOvarian Cancer3
2Not Yet RecruitingTreatmentPancreatic Adenocarcinoma Metastatic1
2Not Yet RecruitingTreatmentPlatinum-sensitive Recurrent BRCA Wild Type Ovarian Cancer1
2Not Yet RecruitingTreatmentRare Tumor1
2Not Yet RecruitingTreatmentRecurrent Osteosarcoma / Sarcoma, Osteogenic1
2RecruitingOtherAdvanced Breast Cancer1
2RecruitingOtherHigh Grade Serous Ovarian Cancer1
2RecruitingOtherNeoplasms, Breast1
2RecruitingScreeningAdvanced Malignant Solid Neoplasm / Ann Arbor Stage III Non-Hodgkin Lymphoma / Ann Arbor Stage IV Non-Hodgkin Lymphoma / Ependymoma, Recurrent / Gliomas, Malignant / Histiocytic Sarcoma (HS) / Juvenile Xanthogranuloma / Langerhans Cell Histiocytosis (LCH) / Recurrent Childhood Rhabdomyosarcoma / Recurrent Ewing Sarcoma / Recurrent Gliomas / Recurrent Hepatoblastoma / Recurrent Langerhans Cell Histiocytosis / Recurrent Malignant Germ Cell Tumor / Recurrent Malignant Solid Neoplasm / Recurrent Medulloblastoma / Recurrent Neuroblastoma / Recurrent Non-Hodgkin Lymphoma / Recurrent Osteosarcoma / Recurrent Peripheral Primitive Neuroectodermal Tumor / Recurrent Primary Central Nervous System Neoplasm / Recurrent Rhabdoid Tumor / Recurrent Soft Tissue Sarcoma / Refractory Ewing Sarcoma / Refractory Glioma / Refractory Hepatoblastoma / Refractory Langerhans cell histiocytosis / Refractory Malignant Germ Cell Tumor / Refractory Malignant Solid Neoplasm / Refractory Medulloblastoma / Refractory Neuroblastoma / Refractory Non-Hodgkin's lymphoma / Refractory Osteosarcoma / Refractory Peripheral Primitive Neuroectodermal Tumor / Refractory Primary Central Nervous System Neoplasm / Refractory Rhabdoid Tumor / Refractory Rhabdomyosarcoma / Rhabdoid Tumors / Stage III Osteosarcoma AJCC v7 / Stage III Soft Tissue Sarcoma AJCC v7 / Stage IV Osteosarcoma AJCC v7 / Stage IV Soft Tissue Sarcoma AJCC v7 / Stage IVA Osteosarcoma AJCC v7 / Stage IVB Osteosarcoma AJCC v7 / Wilms' tumor1
2RecruitingTreatmentAbnormal DNA Repair / Hormone-Resistant Prostate Cancer / Metastatic Hormone Refractory Prostate Cancer / Prostate Cancer Metastatic Castration-Resistant / Stage IV Prostate Cancer1
2RecruitingTreatmentAdenocarcinoma of the Pancreas / Leiomyosarcomas / Mismatch Repair Proficient Colorectal Cancer1
2RecruitingTreatmentAdenocarcinoma, Prostate / Castration Levels of Testosterone / Castration-Resistant Prostate Carcinoma / PSA Level Greater Than or Equal to One / PSA Progression1
2RecruitingTreatmentAdvanced Bladder Carcinoma / Advanced Urothelial Carcinoma / Metastatic Bladder Urothelial Carcinoma / Stage III Bladder Cancer AJCC v8 / Stage IIIA Bladder Cancer AJCC v8 / Stage IIIB Bladder Cancer AJCC v8 / Stage IV Bladder Cancer AJCC v8 / Stage IVA Bladder Cancer AJCC v8 / Stage IVB Bladder Cancer AJCC v8 / Urothelial carcinoma ureter metastatic1
2RecruitingTreatmentAdvanced Breast Cancer2
2RecruitingTreatmentAdvanced Cancers Harbouring Mutations in HRG1
2RecruitingTreatmentAdvanced Gastric Cancer1
2RecruitingTreatmentAdvanced Malignant Solid Neoplasm / Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma / Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma / Gliomas, Malignant / Low Grade Glioma (LGG) / Recurrent Childhood Central Nervous System Neoplasm / Recurrent Childhood Ependymoma / Recurrent Childhood Malignant Germ Cell Tumor / Recurrent Childhood Non-Hodgkin Lymphoma / Recurrent Childhood Rhabdomyosarcoma / Recurrent Childhood Soft Tissue Sarcoma / Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Recurrent Gliomas / Recurrent Hepatoblastoma / Recurrent Langerhans Cell Histiocytosis / Recurrent Malignant Solid Neoplasm / Recurrent Medulloblastoma / Recurrent Neuroblastoma / Recurrent Osteosarcoma / Refractory Childhood Malignant Germ Cell Tumor / Refractory Ependymoma / Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Refractory Glioma / Refractory Hepatoblastoma / Refractory Langerhans cell histiocytosis / Refractory Malignant Glioma / Refractory Malignant Solid Neoplasm / Refractory Medulloblastoma / Refractory Neuroblastoma / Refractory Non-Hodgkin's lymphoma / Refractory Osteosarcoma / Refractory Primary Central Nervous System Neoplasm / Refractory Rhabdomyosarcoma / Refractory Soft Tissue Sarcoma / Rhabdoid Tumors / Wilms' tumor1
2RecruitingTreatmentAdvanced Malignant Solid Neoplasm / Glioblastomas / Recurrent Cholangiocarcinoma / Recurrent Gliomas / Recurrent Malignant Solid Neoplasm / WHO Grade II Glioma / WHO Grade III Glioma1
2RecruitingTreatmentAdvanced Solid Tumors / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)2
2RecruitingTreatmentBRCA Wild Type Platinum Sensitive Recurrent Ovarian Cancer1
2RecruitingTreatmentBRCA1 Gene Mutation / Brca2 Gene Mutation / Ovarian Serous Adenocarcinoma / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma1
2RecruitingTreatmentBreast Cancer1
2RecruitingTreatmentBreast Cancer / ER-Negative PR-Negative HER2-Negative Breast Cancer / ER-Negative PR-Negative HER2-Negative Breast Neoplasms / Metastatic Triple Negative Breast Cancer / Triple Negative Breast Cancer (TNBC) / Triple-Negative Breast Cancer (TNBC) / Triple-Negative Breast Neoplasms1
2RecruitingTreatmentBreast Cancer / Hemangiosarcoma / Neoplasms, Breast / Tumors, Breast1
2RecruitingTreatmentCancer of Unknown Primary Site1
2RecruitingTreatmentCarcinosarcoma / Neoplasms, Endometrial1
2RecruitingTreatmentCholangiocarcinomas1
2RecruitingTreatmentClear Cell Renal Cell Carcinoma / Locally Advanced Malignant Solid Neoplasm / Locally Advanced Pancreatic Cancer / Metastatic Malignant Solid Neoplasm / Metastatic Renal Cell Carcinoma / Pancreatic Cancer Metastatic / Stage III Pancreatic Cancer / Stage III Renal Cell Cancer / Stage IV Pancreatic Cancer / Stage IV Renal Cell Cancer / Urothelial carcinoma ureter metastatic1
2RecruitingTreatmentColorectal Cancers1
2RecruitingTreatmentDebulking Surgical Procedures / Fallopian Tube Cancer / Neoadjuvant Treatment / Ovarian Cancer1
2RecruitingTreatmentA Germline or Somatic BRCA Mutation, or a Deleterious Alteration of Other Genes Involved in Homologous Recombination Repair (HRR) or in MSI Status / ER-positive and HER2-negative Metastatic or Locally Advanced Breast Cancer1
2RecruitingTreatmentEndometrial Cancer / Neoplasms, Endometrial / Uterine Neoplasms1
2RecruitingTreatmentFallopian Tube Endometrioid Tumor / High Grade Fallopian Tube Serous Adenocarcinoma / High Grade Ovarian Serous Adenocarcinoma / Malignant Ovarian Endometrioid Tumor / Platinum-Sensitive Fallopian Tube Carcinoma / Platinum-Sensitive Ovarian Carcinoma / Platinum-Sensitive Primary Peritoneal Carcinoma / Primary Peritoneal High Grade Serous Adenocarcinoma / Recurrent Fallopian Tube Carcinoma / Recurrent Fallopian Tube Endometrioid Adenocarcinoma / Recurrent Ovarian Endometrioid Adenocarcinoma / Recurrent Ovarian Serous Adenocarcinoma / Recurrent Primary Peritoneal Carcinoma / Recurrent Primary Peritoneal Endometrioid Adenocarcinoma1
2RecruitingTreatmentGastro-oesophageal Junction Cancer / Malignant Neoplasm of Esophagus / Malignant Neoplasm of Stomach1
2RecruitingTreatmentGynaecological Cancers1
2RecruitingTreatmentHigh Grade Serous Carcinoma1
2RecruitingTreatmentInflammatory Breast Carcinoma1
2RecruitingTreatmentKidney Cancer Metastatic / Metastatic Renal Cell Carcinoma / Renal Cancers / Renal Carcinoma / Renal Cell Adenocarcinoma1
2RecruitingTreatmentLocally Advanced Unresectable Breast Carcinoma / Metastatic Breast Carcinoma / Stage III Breast Cancer AJCC V7 / Stage IIIA Breast Cancer AJCC v7 / Stage IIIB Breast Cancer AJCC v7 / Stage IIIC Breast Cancer AJCC v7 / Stage IV Breast Cancer AJCC v6 and v71
2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
2RecruitingTreatmentMalignancies / Neoplasms / Tumors1
2RecruitingTreatmentMalignant Neoplasm of Pancreas1
2RecruitingTreatmentMalignant Solid Neoplasms1
2RecruitingTreatmentMalignant Solid Neoplasm / Refractory Cholangiocarcinoma / Refractory Malignant Solid Neoplasm1
2RecruitingTreatmentMesothelioma1
2RecruitingTreatmentMetastatic Hormone Refractory Prostate Cancer1
2RecruitingTreatmentMetastatic Sarcoma / Sarcomas1
2RecruitingTreatmentMetastatic Triple Negative Breast Cancer1
2RecruitingTreatmentMetastatic Urothelial Cancer1
2RecruitingTreatmentNeoplasms, Advanced Solid1
2RecruitingTreatmentOvarian Epithelial Cancer1
2RecruitingTreatmentPancreatic Adenocarcinoma Metastatic / Pancreatic Ductal Adenocarcinoma / Stage III Breast Cancer AJCC V7 / Stage III Lung Non-Small Cell Cancer AJCC v7 / Stage III Lung Small Cell Carcinoma AJCC v7 / Stage III Pancreatic Cancer AJCC v6 and v7 / Stage IIIA Breast Cancer AJCC v7 / Stage IIIA Lung Non-Small Cell Cancer AJCC v7 / Stage IIIA Lung Small Cell Carcinoma AJCC v7 / Stage IIIB Breast Cancer AJCC v7 / Stage IIIB Lung Non-Small Cell Cancer AJCC v7 / Stage IIIB Lung Small Cell Carcinoma AJCC v7 / Stage IIIC Breast Cancer AJCC v7 / Stage IV Breast Cancer AJCC v6 and v7 / Stage IV Lung Non-Small Cell Cancer AJCC v7 / Stage IV Lung Small Cell Carcinoma AJCC v7 / Stage IV Pancreatic Cancer AJCC v6 and v7 / Triple-Negative Breast Carcinoma / Unresectable Pancreatic Carcinoma1
2RecruitingTreatmentPlatinum-resistant Recurrent Ovarian Cancer1
2RecruitingTreatmentProstate1
2RecruitingTreatmentProstate Cancer2
2RecruitingTreatmentProstate Cancer / Prostate Cancer Aggressiveness1
2RecruitingTreatmentRare Tumor / Refractory Tumors1
2RecruitingTreatmentRecurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma1
2RecruitingTreatmentSmall Cell Lung Cancer (SCLC)1
2RecruitingTreatmentTriple Negative Breast Cancer (TNBC)1
2RecruitingTreatmentTumors, Solid1
2SuspendedTreatmentATM Biallelic Inactivation / ATM Gene Mutation / ATM Monoallelic Inactivation / BRCA1 Biallelic Inactivation / BRCA1 Gene Mutation / BRCA2 Biallelic Inactivation / Brca2 Gene Mutation / FANCA Biallelic Inactivation / Homologous Recombination Deficiency / PALB2 Biallelic Inactivation / PALB2 Gene Mutation / Prostate Adenocarcinoma Without Evidence of Neuroendocrine Differentiation / Stage I Prostate Cancer AJCC v8 / Stage II Prostate Cancer AJCC v8 / Stage IIA Prostate Cancer AJCC v8 / Stage IIB Prostate Cancer AJCC v8 / Stage IIC Prostate Cancer AJCC v81
2SuspendedTreatmentBreast Cancer1
2SuspendedTreatmentEndometrial Undifferentiated Carcinoma / Endometrioid Adenocarcinoma / Recurrent Endometrial Serous Adenocarcinoma / Recurrent Uterine Corpus Carcinoma / Stage IV Uterine Corpus Cancer AJCC v7 / Stage IVA Uterine Corpus Cancer AJCC v7 / Stage IVB Uterine Corpus Cancer AJCC v71
2SuspendedTreatmentStage III Uterine Corpus Leiomyosarcoma AJCC v8 / Stage IIIA Uterine Corpus Leiomyosarcoma AJCC v8 / Stage IIIB Uterine Corpus Leiomyosarcoma AJCC v8 / Stage IIIC Uterine Corpus Leiomyosarcoma AJCC v8 / Stage IV Uterine Corpus Leiomyosarcoma AJCC v8 / Stage IVA Uterine Corpus Leiomyosarcoma AJCC v8 / Stage IVB Uterine Corpus Leiomyosarcoma AJCC v81
2TerminatedTreatmentExtensive Stage Lung Small Cell Carcinoma1
2WithdrawnTreatmentFallopian Tube Cancer / Malignant Peritoneal Neoplasm / Ovarian Cancer1
2, 3RecruitingTreatmentBreast Cancer1
2, 3RecruitingTreatmentFallopian Tube Clear Cell Adenocarcinoma / Fallopian Tube Endometrioid Adenocarcinoma / Fallopian Tube Serous Adenocarcinoma / Fallopian Tube Transitional Cell Carcinoma / Fallopian Tube Undifferentiated Carcinoma / Ovarian Clear Cell Adenocarcinoma / Ovarian Endometrioid Adenocarcinoma / Ovarian Seromucinous Carcinoma / Ovarian Serous Adenocarcinoma / Ovarian Transitional Cell Carcinoma / Ovarian Undifferentiated Carcinoma / Primary Peritoneal Serous Adenocarcinoma / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma1
2, 3RecruitingTreatmentTriple Negative Breast Neoplasms1
3Active Not RecruitingTreatmentAdvanced Ovarian Cancer / BRCA Mutation / Complete Response / FIGO Stage III-IV / First Line Platinum Chemotherapy / Newly Diagnosed / Partial Response1
3Active Not RecruitingTreatmentBRCA 1 Gene Mutation / BRCA 2 Gene Mutation / Metastatic Breast Cancer1
3Active Not RecruitingTreatmentBRCA Mutated / Following Complete or Partial Response to Platinum Based Chemotherapy / Platinum Sensitive / Recurrent Ovarian Cancer1
3Active Not RecruitingTreatmentBreast Cancer1
3Active Not RecruitingTreatmentFallopian Tube Clear Cell Adenocarcinoma / Fallopian Tube Transitional Cell Carcinoma / Fallopian Tube Undifferentiated Carcinoma / Ovarian Clear Cell Adenocarcinoma / Ovarian Endometrioid Tumor / Ovarian Seromucinous Carcinoma / Ovarian Serous Tumor / Ovarian Transitional Cell Carcinoma / Ovarian Undifferentiated Carcinoma / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Ovarian Endometrioid Adenocarcinoma / Recurrent Primary Peritoneal Carcinoma1
3Active Not RecruitingTreatmentFollowing Complete or Partial Response to Platinum Based Chemotherapy / Platinum Sensitive / Recurrent Ovarian Cancer1
3Active Not RecruitingTreatmentGermline BRCA1/2 Mutations and / Metastatic Adenocarcinoma of the Pancreas1
3Active Not RecruitingTreatmentGermline BRCA1/2 Mutations / HER2-ve Metastatic Breast Cancer / Somatic BRCA1/2 Mutations1
3Active Not RecruitingTreatmentMalignant Neoplasm of Stomach1
3Active Not RecruitingTreatmentMetastatic Castration Resistant Prostate Cancer1
3Active Not RecruitingTreatmentNon-Germline BRCA Mutated Ovarian Cancer1
3Active Not RecruitingTreatmentOvarian Cancer1
3Active Not RecruitingTreatmentRelapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity1
3Not Yet RecruitingTreatmentOvarian Cancer1
3RecruitingHealth Services ResearchSoft Tissue Sarcoma (STS)1
3RecruitingTreatmentAbdominal wall neoplasm / Fallopian Tube Cancer / Ovarian Cancer1
3RecruitingTreatmentAdvanced Ovarian Cancer1
3RecruitingTreatmentBreast Cancer1
3RecruitingTreatmentCarcinoma, Non-squamous Non-small-cell Lung1
3RecruitingTreatmentCarcinoma, Squamous Cell, Non-small-cell Lung1
3RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Neoplasms, Lung1
3RecruitingTreatmentMetastatic Castration Resistant Prostate Cancer1
3RecruitingTreatmentNeoplasms, Endometrial1
3RecruitingTreatmentOvarian Cancer1
3RecruitingTreatmentOvarian Epithelial Cancer1
3RecruitingTreatmentProstatic Neoplasms1
3WithdrawnTreatmentPlatinum Sensitive Relapsed Ovarian Cancer1
4Active Not RecruitingOtherBRCA or HRR+ Mutated Ovarian Cancer Patients1
4RecruitingTreatmentBreast Cancer / Ovarian Cancer1
Not AvailableActive Not RecruitingNot AvailableRelapsed Ovarian Cancers Patients1
Not AvailableActive Not RecruitingTreatmentOvarian Cancer1
Not AvailableApproved for MarketingNot AvailableOvarian Cancer1
Not AvailableCompletedNot AvailableEndometrial Carcinoma1
Not AvailableNo Longer AvailableNot AvailablePSR Ovarian Cancer With a BRCA Mutation1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral50 mg/1
CapsuleOral50 mg
TabletOral100 mg
TabletOral150 mg
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral150 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8859562No2014-10-142031-08-04Us
US8912187No2014-12-162024-03-12Us
US8143241No2012-03-272027-08-12Us
US7449464No2008-11-112024-10-11Us
US8247416No2012-08-212028-09-24Us
US7151102No2006-12-192022-04-29Us
US7981889No2011-07-192024-10-11Us
US8475842No2013-07-022029-12-31Us
US9566276No2017-02-142024-03-12Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0601 mg/mLALOGPS
logP2.72ALOGPS
logP1.96ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)9.96ChemAxon
pKa (Strongest Basic)-0.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area82.08 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity117.53 m3·mol-1ChemAxon
Polarizability43.81 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phthalazinones. These are compounds containing a phthalazine bearing a ketone group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazanaphthalenes
Sub Class
Benzodiazines
Direct Parent
Phthalazinones
Alternative Parents
2-halobenzoic acids and derivatives / Benzamides / Benzoyl derivatives / Fluorobenzenes / Pyridazines and derivatives / Piperazines / Aryl fluorides / Cyclopropanecarboxylic acids and derivatives / Vinylogous halides / Tertiary carboxylic acid amides
show 8 more
Substituents
Phthalazinone / 2-halobenzoic acid or derivatives / Halobenzoic acid or derivatives / Benzoic acid or derivatives / Benzamide / Benzoyl / Fluorobenzene / Halobenzene / Monocyclic benzene moiety / Benzenoid
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
cyclopropanes, monofluorobenzenes, phthalazines, N-acylpiperazine (CHEBI:83766)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This ...
Gene Name
PARP1
Uniprot ID
P09874
Uniprot Name
Poly [ADP-ribose] polymerase 1
Molecular Weight
113082.945 Da
References
  1. Verhagen CV, de Haan R, Hageman F, Oostendorp TP, Carli AL, O'Connor MJ, Jonkers J, Verheij M, van den Brekel MW, Vens C: Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells. Radiother Oncol. 2015 Sep;116(3):358-65. doi: 10.1016/j.radonc.2015.03.028. Epub 2015 May 13. [PubMed:25981132]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Nad+ adp-ribosyltransferase activity
Specific Function
Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This ...
Gene Name
PARP2
Uniprot ID
Q9UGN5
Uniprot Name
Poly [ADP-ribose] polymerase 2
Molecular Weight
66205.31 Da
References
  1. Verhagen CV, de Haan R, Hageman F, Oostendorp TP, Carli AL, O'Connor MJ, Jonkers J, Verheij M, van den Brekel MW, Vens C: Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells. Radiother Oncol. 2015 Sep;116(3):358-65. doi: 10.1016/j.radonc.2015.03.028. Epub 2015 May 13. [PubMed:25981132]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Nad+ adp-ribosyltransferase activity
Specific Function
Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This ...
Gene Name
PARP3
Uniprot ID
Q9Y6F1
Uniprot Name
Poly [ADP-ribose] polymerase 3
Molecular Weight
60069.7 Da
References
  1. Verhagen CV, de Haan R, Hageman F, Oostendorp TP, Carli AL, O'Connor MJ, Jonkers J, Verheij M, van den Brekel MW, Vens C: Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells. Radiother Oncol. 2015 Sep;116(3):358-65. doi: 10.1016/j.radonc.2015.03.028. Epub 2015 May 13. [PubMed:25981132]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Verhagen CV, de Haan R, Hageman F, Oostendorp TP, Carli AL, O'Connor MJ, Jonkers J, Verheij M, van den Brekel MW, Vens C: Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells. Radiother Oncol. 2015 Sep;116(3):358-65. doi: 10.1016/j.radonc.2015.03.028. Epub 2015 May 13. [PubMed:25981132]
  2. Linparza (olaparib) drug monograph [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Verhagen CV, de Haan R, Hageman F, Oostendorp TP, Carli AL, O'Connor MJ, Jonkers J, Verheij M, van den Brekel MW, Vens C: Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells. Radiother Oncol. 2015 Sep;116(3):358-65. doi: 10.1016/j.radonc.2015.03.028. Epub 2015 May 13. [PubMed:25981132]
  2. Olaparib Health Canada Product Monograph [File]
  3. Olaparib EMA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
Curator comments
This agent is a substrate and inhibitor of P-glycoprotein in vitro, but prescribing information states that this is unlikely to be of clinical significance.
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Olaparib New Zealand Data Sheet [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Olaparib New Zealand Data Sheet [Link]

Drug created on May 14, 2015 14:38 / Updated on July 03, 2020 08:33

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