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

Solid Tumor Clinical Trial

— LODESTAR  

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 Details — Status: Terminated

Administrative data

• NCT number: NCT04171700
• Other study ID #: CO-338-100
• Status: Terminated
• Phase: Phase 2
• Start date: January 16, 2020
• Est. completion date: July 15, 2022

Study information

• Verified date: September 2023
• Source: pharmaand GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 83
• Est. completion date: July 15, 2022
• Est. primary completion date: June 8, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• Rucaparib
Oral rucaparib will be administered twice daily. The starting dose will be 600 mg daily (BID).

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Cancer Surgical Pavilion	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	New York Cancer And Blood Specialists	Bronx	New York
United States	SCRI/Tennessee Oncology - Chattanooga	Chattanooga	Tennessee
United States	Robert H. Lurie Comprehensive Cancer Center of Northwestern University	Chicago	Illinois
United States	Ohio State University	Columbus	Ohio
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	University of Iowa Hospital and Clinics	Iowa City	Iowa
United States	UCLA Medicine Hematology and Oncology	Los Angeles	California
United States	Tennessee Oncology	Nashville	Tennessee
United States	Columbia University Irving Medical Center	New York	New York
United States	Stephenson Cancer Center - The University of Oklahoma	Oklahoma City	Oklahoma
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	New York Cancer and Blood Specialists	Port Jefferson Station	New York
United States	Florida Cancer Specialists	Saint Petersburg	Florida
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Seattle Cancer Care Alliance/University of Washington	Seattle	Washington
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
pharmaand GmbH

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Number of Participants Experiencing Treatment-emergent Adverse Events		From first dose of study drug until disease progression (up to approximately 2 years)
Secondary	Steady State Minimum Concentration [Cmin]	Rucaparib pharmacokinetics	From first dose of study drug until disease progression (up to approximately 2 years)