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EUCTR2018-003007-19

Olaparib Monotherapy in HRRm or HRD Positive Cancer

Data source: WHO (Imported from 22.11.2020)
Changed: 22.11.2020
Disease category:

Health conditions (Data source: WHO)

Homologous recombination repair mutation (HRRm) or Homologous recombination deficiency (HRD) positive cancer
MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864;Therapeutic area: Diseases [C] - Cancer [C04]

Interventions (Data source: WHO)


Product Name: Olaparib
Product Code: AZD2281, KU-0059436
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: OLAPARIB
CAS Number: 763113-22-0
Current Sponsor code: MK-7339
Other descriptive name: OLAPARIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Product Name: Olaparib
Product Code: AZD2281, KU-0059436
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: OLAPARIB
CAS Number: 763113-22-0
Current Sponsor code: MK-7339
Other descriptive name: OLAPARIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Inclusion/Exclusion Criteria (Data source: WHO)

Inclusion criteria:
1. Participant has a histologically- or cytologically-confirmed advanced (metastatic and/or unresectable) solid tumor (except breast or ovarian cancers whose tumor has a germline or somatic BRCA mutation) that is not eligible for curative treatment and for which standard of care therapy has failed. Participants must have progressed on or be intolerant to standard of care therapies that are known to provide clinical benefit. There is no limit on the number of prior treatment regimens
2. Participant has either centrally-confirmed known or suspected deleterious mutations in at least 1 of the specified 15 genes involved in HRR (ie, BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L) or centrally-confirmed HRD based on the Lynparza HRR-HRD assay
3. If participants have received prior platinum (cisplatin, carboplatin, oxaliplatin, etc. either as monotherapy or in combination) for advanced (metastatic and/or unresectable) solid tumor, they are eligible to enter the study provided there has been no evidence of disease progression during the platinum chemotherapy
4. Participant has measurable disease per RECIST 1.1 or PCWG-modified RECIST 1.1 as assessed by the local site Investigator/radiology and confirmed by BICR. BICR must confirm the presence of radiologically measurable disease based on RECIST 1.1 or PCWG-modified RECIST 1.1 for the participant to be eligible for the study. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
5. Participant is able to provide a newly obtained core or excisional biopsy of a tumor lesion or either an archival formalin-fixed paraffin embedded (FFPE) tumor tissue block or slides. A newly obtained biopsy is preferred, but not required if archival tissue is available for analysis
6. Participant has a life expectancy of at least 3 months
7. Participant is Male or Female who is at least 18 years of age at the time of signing the informed consent
8. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1, as assessed within 3 days of treatment initiation
9. A male participant must agree to use contraception during the treatment period and for at least 90 days (3 months), corresponding to time needed to eliminate any study intervention(s) (ie, olaparib) plus a spermatogenesis cycle, after the last dose of study intervention and refrain from donating sperm during this period
10. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
a) Not a woman of childbearing potential (WOCBP)
OR
b) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 30 days (1 month) after the last dose of study intervention, corresponding to time needed to eliminate any study intervention(s (ie, olaparib) plus 30 days (a menstruation cycle) for study interventions with risk of genotoxicity
11. The participant (or legally acceptable representative if applicable) provides written informed consent for the study. The participant may also provide consent for FBR. However, the participant may participate in the main study without participating in FBR
12. Participant has adequate organ function
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age r
Exclusion criteria:
1. Participant has a known additional malignancy that is progressing or has required active treatment in the last 5 years
2. Participant has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML
3. Participant has persistent toxicities (>CTCAE Grade 2) caused by previous cancer therapy, excluding alopecia
4. Participant has known central nervous system (CNS) metastases and/or carcinomatous meningitis
5. Participant has an active infection requiring systemic therapy
6. Participant has a history or current evidence of any condition (eg, cytopenia, transfusion-dependent anemia, or thrombocytopenia), therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant’s involvement for the full duration of the study, or is not in the best interest of the participant to be involved, in the opinion of the treating Investigator
7. Participant received colony-stimulating factors (eg, granulocyte colony-stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 28 days prior to the first dose of study intervention
8. Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent
9. Participant has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study
10. Participant has a known history of human immunodeficiency virus (HIV) infection. Testing for HIV at screening is only required if mandated by local health authority.
11. Participant has known active hepatitis (ie, Hepatitis B or C)
a) Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Participants with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible
b) Participants positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA
12. Participant is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel obstruction, malabsorption)
13. Participant has received prior therapy with olaparib or with any other PARP inhibitor.
14. Participant has a known hypersensitivity to the components or excipients in olaparib
15. Participant is currently receiving either strong (eg, itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 2 weeks
16. Participant is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John’s Wort) or moderate

Further information on the trial in WHO primary registry

https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-003007-19

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2018-003007-19-GB

Further information on trial

Date trial registered

14.05.2019

Incorporation of the first participant

14.05.2019

Recruitment status

Authorised-recruitment may be ongoing or finished

Academic title (Data source: WHO)

A Phase 2 Study of Olaparib Monotherapy in Participants with Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer - Olaparib Monotherapy in HRRm or HRD Positive Cancer

Type of trial (Data source: WHO)

Interventional clinical trial of medicinal product

Design of the trial (Data source: WHO)

Controlled: noRandomised: noOpen: noSingle blind: noDouble blind: noParallel group: noCross over: noOther: noIf controlled, specify comparator, Other Medicinial Product: noPlacebo: noOther: noNumber of treatment arms in the trial: 1

Phase (Data source: WHO)

Human pharmacology (Phase I): noTherapeutic exploratory (Phase II): yesTherapeutic confirmatory - (Phase III): noTherapeutic use (Phase IV): no

Primary end point (Data source: WHO)

Main Objective: To evaluate the objective response rate (ORR) as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) or Prostate Cancer Working Group (PCWG)-modified RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, following olaparib administration in Cohort 1 and Cohort 2;Secondary Objective: -To evaluate the duration of response(DOR)as assessed by BICR according to RECIST1.1 or PCWGmodified RECIST1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, following olaparib administration in Cohort 1 and 2
-To evaluate overall survival(OS), following administration of olaparib in Cohort 1 and 2
-To evaluate progression free survival(PFS)as assessed by BICR according to RECIST1.1 or PCWGmodified RECIST1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, following olaparib administration in Cohort 1 and 2
-To evaluate the safety and tolerability of olaparib
-To evaluate the ORR, DOR, OS, and PFS in participants who are HRRm, HRD positive, and in all participants regardless of biomarker status following olaparib administration in Cohort 1 and 2
-To assess time to earliest progression by CA-125 following olaparib administration in participants with BRCA1/2 non mutated ovarian cancer;Primary end point(s): Objective response rate (ORR) based on RECIST 1.1 or PCWG-modified RECIST 1.1 (participants with prostate cancer) as assessed by blinded independent central review;Timepoint(s) of evaluation of this end point: The primary analysis will be conducted when all enrolled participants have at least 9 months follow-up

Secundary end point (Data source: WHO)

Secondary end point(s): 1) Duration of response(DOR)
2) Evaluate overall survival(OS
3) Progression free survival(PFS)
;Timepoint(s) of evaluation of this end point: To be determined

Contact information (Data source: WHO)

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Trial results (Data source: WHO)

Results summary

A Phase 2 Study of Olaparib Monotherapy in Participants with Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

no information available yet

Trial sites

Countries (Data source: WHO)

Argentina, Australia, Canada, Colombia, Denmark, France, Guatemala, Ireland, Israel, Italy, Japan, Korea, Mexico, New Zealand, Peru, Republic of, Romania, Russian Federation, Spain, Switzerland, Turkey, United Kingdom, United States

Contact for further information on the trial

Contact for general information (Data source: WHO)

Global Clinical Trial Operations
Hertford Road
Merck Sharp & Dohme (UK) Ltd.
+44 7969 847981
marie.pullen@msd.com

Contact for scientific information (Data source: WHO)

Global Clinical Trial Operations
Hertford Road
Merck Sharp & Dohme (UK) Ltd.
+44 7969 847981
marie.pullen@msd.com

Principal Sponsor/Investigator

Principal sponsor (Data source: WHO)

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Further trial identification numbers

Secondary ID (Data source: WHO)

MK-7339-002
2018-003007-19-DK