A Study to Evaluate Rucaparib in Participants With Solid Tumors and With Deleterious Mutations in HRR Genes

Study Overview
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Brief Summary
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A Phase 2, open-label, single-arm trial to evaluate the response of rucaparib in participants with various solid tumors and with deleterious mutations in Homologous Recombination Repair (HRR) genes.

Official Title
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A Phase 2 Multicenter, Open-label Study of Rucaparib as Treatment for Solid Tumors Associated With Deleterious Mutations in Homologous Recombination Repair Genes

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: Rucaparib


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Unresectable, locally advanced or metastatic solid tumor and relapsed/progressive disease Measurable disease per RECIST v1.1 or modified RECIST v1.1 and PCWG3 (for prostate cancer) Have a deleterious mutation (germline or somatic) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, BARD1, BRIP1, FANCA, NBN, RAD51 or RAD51B. Note: Breast cancer patients that are HER2 negative and have germline BRCA1 or BRCA2 mutations AND patients with epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer or metastatic castration-resistant prostate cancer with BRCA1 or BRCA2 mutations are ineligible for this trial. At least one prior line of therapy extending overall survival or standard of care therapy for advanced disease. Note: Some tumor types have specific inclusion/exclusion criteria for previous treatments. ECOG 0 or 1 Tumor tissue available for genomic analysis, or must be willing to have a biopsy if no archival tumor tissue available Adequate organ function Life expectancy of 4 months Key Exclusion Criteria: Active central nervous system brain metastases, leptomeningeal disease or primary tumor of CNS origin Active second malignancy (Exceptions: Successfully treated malignancy with no active disease for 1 year, surgically cured and/or low-risk tumors, or patients receiving ongoing anticancer hormonal therapy for a previously treated cancer) Pre-existing gastrointestinal disorders/conditions interfering with ingestion/absorption of rucaparib Prior treatment with a PARP inhibitor More than 3 prior lines of chemotherapy in the locally advanced/metastatic setting History of myelodysplastic syndrome or acute myeloid leukemia

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rucaparib<br>Eligible participants will be enrolled in either Cohort A or Cohort B. Cohort A: Up to 200 participants with deleterious mutations in BRCA1, BRCA2, PALB2, RAD51C or RAD51D. Cohort B (Exploratory): Up to 20 participants with deleterious mutations in BARD1, BRIP1, FANCA, NBN, RAD51 or RAD51B. | Drug: Rucaparib<br>* Oral rucaparib will be administered twice daily. The starting dose will be 600 mg daily (BID).<br>* Other names: AG 014447;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response Rate by Investigator | Best overall response rate as assessed by the investigator by RECIST v1.1 (or by RECIST v1.1 and PCWG3 in participants with advanced prostate cancer). | From first dose of study drug until disease progression (up to approximately 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate by Independent Radiology Review | Best overall response rate by independent radiology review by RECIST v1.1 (or by RECIST v1.1 and PCWG3 in participants with advanced prostate cancer). | From first dose of study drug until disease progression (up to approximately 2 years) | 
| Duration of Response | Measure of clinical benefit, defined as the time from initial tumor response to documented tumor progression. | From first dose of study drug until disease progression (up to approximately 2 years) | 
| Disease Control Rate | Measure of clinical benefit, defined as the percentage of complete response (CR), partial response (PR), and stable disease (SD) beyond 16 weeks. | From first dose of study drug until disease progression (up to approximately 2 years) | 
| Progression-free Survival | Measure of clinical benefit, defined as the duration from study enrollment to objective tumor progression. Progression was defined using RECIST v1.1, as a 20% increase in the sum of diameters of target lesions (and an absolute increase of at least 5 mm), or unequivocal progression of existing non-target lesions, or the appearance of new lesions. For mCRPC disease, the PCWG3 confirmed bone disease progression criteria (2+2) were also incorporated. | From first dose of study drug until disease progression (up to approximately 2 years) | 
| Overall Survival | Measure of clinical benefit, defined as the duration from study enrollment to death. | From first dose of study drug until disease progression (up to approximately 2 years) | 
| Number of Participants Experiencing Treatment-emergent Adverse Events |  | From first dose of study drug until disease progression (up to approximately 2 years) | 
| Steady State Minimum Concentration [Cmin] | Rucaparib pharmacokinetics | From first dose of study drug until disease progression (up to approximately 2 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HRR, rucaparib, PARPi, rare tumor, solid tumor, CO-338, ovarian cancer, prostate cancer, pancreatic cancer, breast cancer, lung cancer, colon cancer, gastric cancer, bladder cancer, colorectal cancer, PARP inhibitor, homologous recombination, DNA repair, LODESTAR, germline, somatic, BRCA1, BRCA2, PALB2, RAD51C, RAD51D, BARD1, BRIP1, FANCA, RAD51, RAD51B, sarcoma, HRD, platinum sensitive, platinum resistant, primary peritoneal cancer, fallopian tube cancer, tumor agnostic, basket study, basket trial, metastatic, locally advanced, esophageal cancer, leiomyosarcoma, ampullary carcinoma, carcinosarcoma, endometrial cancer, cervical cancer