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.
- Conditions
- -C887 Other malignant immunoproliferative diseasesOther malignant immunoproliferative diseasesC887
- Registration Number
- PER-046-18
- Lead Sponsor
- Merck Sharp & Dohme Corp., una subsidiaria de Mer·ck & Co. Inc.,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 15
1. Participant has a histologically- or cytologically-confirmed advanced solid tumor that is not eligible for curative treatment and for which standard of care therapy has failed. 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 or centrally-confirmed HRD based on the Lynparza HRR-HRD assay.
3.If participants have received prior platinum for advanced 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.
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,
corresponding to time needed to eliminate any study intervention(s) plus a spermatogenesis cycle, after the last dose of study intervention and refrain from donating sperm during this period. Refer to Appendix 5 for additional guidance.
10.A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
11.The participant 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, all screening laboratory tests should be performed within 10 days prior to the first dose of study
Intervention.
Please refer to the protocol for more information
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, 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 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, 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)
12.Participant is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption.
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 or moderate 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 or moderate inducers of CYP3A4 that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents.
17.Participant has received previous allogenic bone-marrow transplant or double umbilical cord transplantation (dUCBT).
18.Participant has received a whole blood transfusion in the last 120 days prior to entry to the study. Packed red blood cells and platelet transfusions are acceptable if not performed within 28 days of the first dose of study intervention.
19. Participant is currently enrolled in and receiving study therapy, was enrolled in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks (28 days) of the first dose of study intervention.
20.Participant either had major surgery within 2 weeks of starting study intervention or has not recovered from any effects of any major surgery.
21.Participant is involved in the planning and/or conduct of the study.
22.Participant, in the judgement of the Investigator, is unlikely to comply with the study procedures, restrictions, and requirements of the study.
Please refer to the protocol for more information.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name:Clopper-Pearson method<br>Measure:Objective Response Rate ORR per RECIST 1.1 or PCWG-modified RECIST 1.1 (participants with prostate cancer) by BICR.<br>Timepoints:The primary analysis will be conducted when all enrolled<br>participants have at least 9 months follow-up. The final analysis will be conducted when all enrolled participants have at least 24 months follow-up.<br>
- Secondary Outcome Measures
Name Time Method <br>Outcome name:Kaplan-Meier<br>Measure:Objective Response (OR)<br>Timepoints:The primary analysis will be conducted when all enrolled participants have at least 9 months follow-up. The final analysis will be conducted when all enrolled participants have at least 24 months follow-up.<br>;<br>Outcome name:Kaplan-Meier<br>Measure:Duration of Response (DOR)<br>Timepoints:The primary analysis will be conducted when all enrolled<br>participants have at least 9 months follow-up. The final analysis will be conducted when all enrolled participants have at least 24 months follow-up.<br>;<br>Outcome name:Kaplan-Meier<br>Measure:Overall Survival (OS)<br>Timepoints:The primary analysis will be conducted when all enrolled participants have at least 9 months follow-up. The final analysis will be conducted when all enrolled participants have at least 24 months follow-up.<br>