Clinical trial NCT04171700: A Study to Evaluate Rucaparib in Participants 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Solid Tumor
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
Lead sponsor: pharmaand GmbH
Sponsor class: INDUSTRY
First posted: 2019-11-21
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Best Overall Response Rate by Investigator
timeFrame: From first dose of study drug until disease progression (up to approximately 2 years)
Secondary outcomes:
measure: Overall Response Rate by Independent Radiology Review
timeFrame: From first dose of study drug until disease progression (up to approximately 2 years)
measure: Duration of Response
timeFrame: From first dose of study drug until disease progression (up to approximately 2 years)
measure: Disease Control Rate
timeFrame: From first dose of study drug until disease progression (up to approximately 2 years)
measure: Progression-free Survival
timeFrame: From first dose of study drug until disease progression (up to approximately 2 years)
measure: Overall Survival
timeFrame: From first dose of study drug until disease progression (up to approximately 2 years)
measure: Number of Participants Experiencing Treatment-emergent Adverse Events
timeFrame: From first dose of study drug until disease progression (up to approximately 2 years)
measure: Steady State Minimum Concentration [Cmin]
timeFrame: From first dose of study drug until disease progression (up to approximately 2 years)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medicine Hematology and Oncology
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center of Northwestern University
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics
state: Iowa
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Cancer Surgical Pavilion
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Bronx
country: United States
facility: New York Cancer And Blood Specialists
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Port Jefferson Station
country: United States
facility: New York Cancer and Blood Specialists
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center - The University of Oklahoma
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Chattanooga
country: United States
facility: SCRI/Tennessee Oncology - Chattanooga
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance/University of Washington
state: Washington
Study officials:
affiliation: University of Pennsylvania
name: Kim Reiss-Binder, MD
role: PRINCIPAL_INVESTIGATOR
References: