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

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

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.

Study Overview

• Status: Terminated
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: Rucaparib

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90024
      • UCLA Medicine Hematology and Oncology
    • San Francisco, California, United States, 94158
      • UCSF Helen Diller Family Comprehensive Cancer Center
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Robert H. Lurie Comprehensive Cancer Center of Northwestern University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospital and Clinics
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Cancer Surgical Pavilion
  • New York
    • Bronx, New York, United States, 10469
      • New York Cancer and Blood Specialists
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center
    • Port Jefferson Station, New York, United States, 11776
      • New York Cancer and Blood Specialists
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center - The University of Oklahoma
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • SCRI/Tennessee Oncology - Chattanooga
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance/University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Rucaparib; Oral rucaparib will be administered twice daily. The starting dose will be 600 mg daily (BID).; Other Names: Rubraca; CO-338; PF 01367338; Rucaparib camsylate; Rucaparib tablets; AG 014447

What is the study measuring?

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
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)
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: pharmaand GmbH
• Investigators: Principal Investigator: Kim Reiss-Binder, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2020
• Primary Completion (Actual): June 8, 2022
• Study Completion (Actual): July 15, 2022

Study Registration Dates

• First Submitted: November 19, 2019
• First Submitted That Met QC Criteria: November 19, 2019
• First Posted (Actual): November 21, 2019

Study Record Updates

• Last Update Posted (Actual): October 2, 2023
• Last Update Submitted That Met QC Criteria: September 29, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: colorectal cancer; breast cancer; lung cancer; endometrial cancer; prostate cancer; PARP inhibitor; colon cancer; esophageal cancer; bladder cancer; ovarian cancer; fallopian tube cancer; primary peritoneal cancer; platinum resistant; gastric cancer; pancreatic cancer; solid tumor; metastatic; BRCA2; BRCA1; PALB2; cervical cancer; leiomyosarcoma; rare tumor; sarcoma; HRR; locally advanced; carcinosarcoma; platinum sensitive; PARPi; CO-338; germline; HRD; rucaparib; homologous recombination; DNA repair; somatic; LODESTAR; RAD51C; RAD51D; BARD1; BRIP1; FANCA; RAD51; RAD51B; tumor agnostic; basket study; basket trial; ampullary carcinoma
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Rucaparib
• Other Study ID Numbers: CO-338-100

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

De-identified datasets for study results will be made available to qualified researchers in compliance with applicable privacy laws and data protection regulations.

Data will be provided by Clovis Oncology.

• IPD Sharing Time Frame: Data will be made available to qualified researchers after the primary, secondary, and/or exploratory outcomes of the study are reported or published and for 1 year thereafter.
• IPD Sharing Access Criteria: Requests for de-identified datasets will be made available to qualified researchers following submission of a methodologically sound proposal to medinfo@clovisoncology.com.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No