A Study to Evaluate Rucaparib in Participants With Solid Tumors and With Deleterious Mutations in HRR Genes
- Registration Number
- NCT04171700
- Lead Sponsor
- pharmaand GmbH
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 83
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Rucaparib Rucaparib 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.
- Primary Outcome Measures
Name Time Method Best Overall Response Rate by Investigator From first dose of study drug until disease progression (up to approximately 2 years) 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).
- Secondary Outcome Measures
Name Time Method Disease Control Rate From first dose of study drug until disease progression (up to approximately 2 years) Measure of clinical benefit, defined as the percentage of complete response (CR), partial response (PR), and stable disease (SD) beyond 16 weeks.
Overall Response Rate by Independent Radiology Review From first dose of study drug until disease progression (up to approximately 2 years) 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).
Progression-free Survival From first dose of study drug until disease progression (up to approximately 2 years) 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.
Number of Participants Experiencing Treatment-emergent Adverse Events From first dose of study drug until disease progression (up to approximately 2 years) Duration of Response From first dose of study drug until disease progression (up to approximately 2 years) Measure of clinical benefit, defined as the time from initial tumor response to documented tumor progression.
Overall Survival From first dose of study drug until disease progression (up to approximately 2 years) Measure of clinical benefit, defined as the duration from study enrollment to death.
Steady State Minimum Concentration [Cmin] From first dose of study drug until disease progression (up to approximately 2 years) Rucaparib pharmacokinetics
Trial Locations
- Locations (18)
University of Iowa Hospital and Clinics
🇺🇸Iowa City, Iowa, United States
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
New York Cancer and Blood Specialists
🇺🇸Port Jefferson Station, New York, United States
New York Cancer And Blood Specialists
🇺🇸Bronx, New York, United States
UCLA Medicine Hematology and Oncology
🇺🇸Los Angeles, California, United States
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
🇺🇸Chicago, Illinois, United States
Beth Israel Deaconess Medical Cancer Surgical Pavilion
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Seattle Cancer Care Alliance/University of Washington
🇺🇸Seattle, Washington, United States
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Stephenson Cancer Center - The University of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
SCRI/Tennessee Oncology - Chattanooga
🇺🇸Chattanooga, Tennessee, United States
Florida Cancer Specialists
🇺🇸Saint Petersburg, Florida, United States
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Ohio State University
🇺🇸Columbus, Ohio, United States