Olaparib Monotherapy in HRRm or HRD Positive Cancer

• Register: EUCTR
• Last refreshed on: 5 January 2021
• Main ID: EUCTR2018-003007-19-GB
• Date of registration: 14/05/2019
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
• Public title: Olaparib Monotherapy in HRRm or HRD Positive Cancer
• Scientific title: 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
• Date of first enrolment: 14/05/2019
• Target sample size: 390
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-003007-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Global Clinical Trial Operations
• Affiliation: Merck Sharp & Dohme (UK) Ltd.

• Name: Global Clinical Trial Operations
• Affiliation: Merck Sharp & Dohme (UK) Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
Cohorts 1 and 2:
1. Participant has a histologically- or cytologically-confirmed advanced (metastatic and/or unresectable) solid tumor (except ovarian cancer whose tumor has a germline or somatic BRCA mutation and breast cancer whose tumor has a germline BRCA) 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 or =4 weeks of completing the platinum-containing regimen.
Cohorts 1, 2 and 3:
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 95 days (3 months and 5 days), 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:
-Is not a woman of childbearing potential (WOCBP)
OR
-Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 180 days (6 months) after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) i
Exclusion criteria:
Participant
1. has a known additional malignancy that is progressing or has required active treatment in the last 5 years
2. has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML
3. has persistent toxicities (>CTCAE Grade 2) caused by previous cancer therapy, excluding alopecia
4. has known central nervous system (CNS) metastases and/or carcinomatous meningitis
5. has an active infection requiring systemic therapy
6. 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. 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. 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. has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study
10. 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. 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. is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel obstruction, malabsorption)
13. has received prior therapy with olaparib or with any other PARP inhibitor.
14. has a known hypersensitivity to the components or excipients in olaparib
15. 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. is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John’s Wort) or moderate (eg. bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 5 week

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Homologous recombination repair mutation (HRRm) or Homologous recombination deficiency (HRD) positive cancer
MedDRA version: 21.1 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000004864

Intervention(s)

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-

Primary Outcome(s)

Main Objective: To evaluate the objective response rate (ORR) as assessed by blinded independent central review (BICR) according to modified Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) or Prostate Cancer Working Group (PCWG)-modified RECIST 1.1, following olaparib administration in Cohort 1, Cohort 2 and Cohort 3.

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

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

Secondary Objective: To evaluate
-DOR as assessed by BICR according to modified RECIST 1.1 or PCWG-modified RECIST 1.1, following olaparib administration in Cohorts 1, 2 and 3.
-OS, following administration of olaparib in Cohorts 1, 2 and 3.
-PFS as assessed by BICR according to modified RECIST 1.1 or PCWG-modified RECIST 1.1, following olaparib administration in Cohorts 1, 2 and 3.
-the safety and tolerability of olaparib in cohorts 1, 2 and 3.
-the ORR, DOR, OS, and PFS in participants who are (1) HRRm, (2) HRD positive, and (3) in all participants regardless of biomarker status following olaparib administration in Cohorts 1 and 2.
-time to earliest progression by CA-125 following olaparib administration in participants with BRCA1/2 non-mutated ovarian cancer.
-the PSA response rate to olaparib administration in participants with prostate cancer.
-progression-free survival after next-line treatment (PFS2), as assessed by the investigator, in participants with sBRCAm breast cancer.

Secondary Outcome(s)

Secondary end point(s): 1) Duration of response(DOR)
2) Evaluate overall survival(OS
3) Progression free survival(PFS)
4) Progression Free Survival after next-line treatment (PFS2)

Timepoint(s) of evaluation of this end point: To be determined

Secondary ID(s)

MK-7339-002

2018-003007-19-DK

Source(s) of Monetary Support

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

Ethics review

Status: Approved
Approval date: 14/05/2019
Contact: