Description:
A Phase 2, open-label, single-arm trial to evaluate the response of rucaparib in patients
with various solid tumors and with deleterious mutations in Homologous Recombination Repair
(HRR) genes.
Title
- Brief Title: A Study to Evaluate Rucaparib in Patients With Solid Tumors and With Deleterious Mutations in HRR Genes
- Official Title: A Phase 2 Multicenter, Open-label Study of Rucaparib as Treatment for Solid Tumors Associated With Deleterious Mutations in Homologous Recombination Repair Genes
Clinical Trial IDs
- ORG STUDY ID:
CO-338-100
- NCT ID:
NCT04171700
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Rucaparib | Rubraca, Rucaparib camsylate, Rucaparib tablets, CO-338, PF 01367338, AG 014447 | Rucaparib |
Purpose
A Phase 2, open-label, single-arm trial to evaluate the response of rucaparib in patients
with various solid tumors and with deleterious mutations in Homologous Recombination Repair
(HRR) genes.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Rucaparib | Experimental | Eligible patients will be enrolled in either Cohort A or Cohort B.
Cohort A: Up to 200 patients with deleterious mutations in BRCA1, BRCA2, PALB2, RAD51C or RAD51D.
Cohort B (Exploratory): Up to 20 patients with deleterious mutations in BARD1, BRIP1, FANCA, NBN, RAD51 or RAD51B. | |
Eligibility Criteria
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Best Overall Response Rate by Investigator |
| Time Frame: | From first dose of study drug until disease progression (up to approximately 2 years) |
| Safety Issue: | |
| Description: | Best overall response rate as assessed by the investigator by RECIST v1.1 (or by RECIST v1.1 and PCWG3 in patients with advanced prostate cancer). |
Secondary Outcome Measures
| Measure: | Overall Response Rate by Independent Radiology Review |
| Time Frame: | From first dose of study drug until disease progression (up to approximately 2 years) |
| Safety Issue: | |
| Description: | Best overall response rate by independent radiology review by RECIST v1.1 (or by RECIST v1.1 and PCWG3 in patients with advanced prostate cancer) |
| Measure: | Duration of Response |
| Time Frame: | From first dose of study drug until disease progression (up to approximately 2 years) |
| Safety Issue: | |
| Description: | Measure of clinical benefit, defined as the time from initial tumor response to documented tumor progression. |
| Measure: | Disease Control Rate |
| Time Frame: | From first dose of study drug until disease progression (up to approximately 2 years) |
| Safety Issue: | |
| Description: | Measure of clinical benefit, defined as the percentage of complete response (CR), partial response (PR), and stable disease (SD) beyond 16 weeks. |
| Measure: | Progression-Free Survival |
| Time Frame: | From first dose of study drug until disease progression (up to approximately 2 years) |
| Safety Issue: | |
| Description: | Measure of clinical benefit, defined as the duration from study enrollment to objective tumor progression. |
| Measure: | Overall Survival |
| Time Frame: | From first dose of study drug until disease progression (up to approximately 2 years) |
| Safety Issue: | |
| Description: | Measure of clinical benefit, defined as the duration from study enrollment to death. |
| Measure: | Safety and Tolerability of rucaparib |
| Time Frame: | From first dose of study drug until disease progression (up to approximately 2 years) |
| Safety Issue: | |
| Description: | Incidence of AEs, clinical lab abnormalities, and dose modifications. |
| Measure: | Steady state minimum concentration [Cmin] |
| Time Frame: | From first dose of study drug until disease progression (up to approximately 2 years) |
| Safety Issue: | |
| Description: | Rucaparib PK |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Clovis Oncology, Inc. |
Trial Keywords
- 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
- HRR
- 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
Last Updated
March 26, 2021
