A Study of Rucaparib in Patients With Pancreatic Cancer and a Known Deleterious BRCA Mutation

A Phase 2, Open-Label Study of Rucaparib in Patients With Pancreatic Cancer and a Known Deleterious BRCA Mutation

The purpose of this study is to determine whether oral rucaparib is effective in the treatment of patients with locally advanced or metastatic pancreatic cancer and a known deleterious BRCA mutation.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer; Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Drug: Rucaparib

Detailed Description

Rucaparib is an orally available, small molecule inhibitor of poly-adenosine diphosphate [ADP] ribose polymerase (PARP) that inhibits a specific DNA repair pathway known as base excision repair (BER). PARP inhibitors (PARPi) have been shown to effectively kill tumors with a defect in BRCA1 or BRCA2. Clinical benefit has been observed in patients with a gBRCA mutation as well as in those with a somatic BRCA (sBRCA) mutation. Clinical data have also shown that pancreatic cancer patients with a gBRCA mutation benefit from PARPi treatment. Clinical activity of PARP inhibitors in BRCA-mutated pancreatic cancer combined with the paucity of 2nd line therapies support evaluation of rucaparib in pancreatic cancer patients known to harbor a deleterious BRCA mutation.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel, 31096
    • Rambam Healthcare Campus
  • Jerusalem, Israel, 91120
    • Hadassah Hebrew University Hospital (Sharett Institute of Oncology)
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10012
      • New York University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed diagnosis of pancreatic cancer (ductal adenocarcinoma and related subtypes eligible; endocrine and neuroendocrine tumors excluded)
• Received at least 1, but no more than 2, chemotherapy-based regimens for locally advanced or metastatic disease and has relapsed or progressive disease. Patients no longer able to continue treatment with chemotherapy due to intolerable toxicity may be considered for study participation provided that radiology assessment confirms either stable disease or disease progression (i.e. no response to treatment)
• Documented deleterious or suspected deleterious (or equivalent interpretation) BRCA mutation (germline or somatic) as assessed by a local laboratory
• Measurable disease

Exclusion Criteria:

• Presence of another active cancer
• Prior treatment with any PARP inhibitor, including rucaparib. Patients treated with prior iniparib are eligible.
• Symptomatic and/or untreated central nervous system metastases.
• Clinical evidence of malabsorption and/or any other gastrointestinal disorder or defect that would, in the opinion of the investigator, interfere with the absorption of rucaparib.

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; All patients will take oral tablets twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole.	Drug: Rucaparib; All patients will take oral tablets twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole.; Other Names: CO-338; PF 01367338; AG 14699

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Response Rate (ORR) per RECIST v1.1 as assessed by the investigator	Screening, within 7 days prior to the start of every 3rd cycle of treatment, and Treatment Discontinuation Visit. Study to last for ~3 years.

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Response Rate (ORR) per RECIST v1.1 as assessed by independent radiology review	Screening, within 7 days prior to the start of every 3rd cycle of treatment, and Treatment Discontinuation Visit. Study to last for ~3 years.
Duration of Response (DOR) by RECIST v1.1	Screening, within 7 days prior to the start of every 3rd cycle of treatment, and Treatment Discontinuation Visit. Study to last for ~3 years.
PFS defined as the occurrence of disease progression according to RECIST v1.1, as assessed by the investigator, or death from any cause	Screening, within 7 days prior to the start of every 3rd cycle of treatment, and Treatment Discontinuation Visit. Study to last for ~3 years.
Overall Survival (OS)	To be performed continually from first dose of study drug through discontinuation, then every 4 weeks until death, loss to follow-up, withdrawal of consent from study, or closure of the study. Study to last for ~3 years.
Incidence of adverse events (AEs), clinical laboratory abnormalities, and dose modifications	Continuously from signing of informed consent to 28 days after the last dose. Study to last for ~3 years.
Trough (Cmin) level rucaparib concentrations	Cycle 1 Day 15, Cycle 2 Day 15, Cycle 3 Day 1, and Cycle 4 Day 1. Study to last for ~3 years.

Collaborators and Investigators

• Sponsor: zr Pharma & GmbH
• Investigators: Study Director: Heidi Giordano, Clovis Oncology, Inc.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: January 20, 2014
• First Submitted That Met QC Criteria: January 20, 2014
• First Posted (Estimated): January 22, 2014

Study Record Updates

• Last Update Posted (Estimated): June 13, 2023
• Last Update Submitted That Met QC Criteria: June 7, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: PARP inhibitor; BRCA mutation; BRCA; CO-338; Clovis; Clovis Oncology; germline BRCA; somatic BRCA; rucaparib; PF 01367338; AG 14699; RucaPanc
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Rucaparib
• Other Study ID Numbers: CO-338-023