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

• ClinicalTrials.gov Identifier: NCT02042378
• Recruitment Status: Completed
• First Posted: January 22, 2014
• Last Update Posted: January 27, 2020
• Sponsor: Clovis Oncology, Inc.
• Information provided by (Responsible Party): Clovis Oncology, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pancreatic Cancer; Pancreatic Ductal Adenocarcinoma	Drug: Rucaparib	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-Label Study of Rucaparib in Patients With Pancreatic Cancer and a Known Deleterious BRCA Mutation
• Study Start Date: April 2014
• Actual Primary Completion Date: April 2016
• Actual Study Completion Date: May 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate (ORR) per RECIST v1.1 as assessed by the investigator [ Time Frame: 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 :

1. Overall Response Rate (ORR) per RECIST v1.1 as assessed by independent radiology review [ Time Frame: Screening, within 7 days prior to the start of every 3rd cycle of treatment, and Treatment Discontinuation Visit. Study to last for ~3 years. ]
2. Duration of Response (DOR) by RECIST v1.1 [ Time Frame: Screening, within 7 days prior to the start of every 3rd cycle of treatment, and Treatment Discontinuation Visit. Study to last for ~3 years. ]
3. PFS defined as the occurrence of disease progression according to RECIST v1.1, as assessed by the investigator, or death from any cause [ Time Frame: Screening, within 7 days prior to the start of every 3rd cycle of treatment, and Treatment Discontinuation Visit. Study to last for ~3 years. ]
4. Overall Survival (OS) [ Time Frame: 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. ]
5. Incidence of adverse events (AEs), clinical laboratory abnormalities, and dose modifications [ Time Frame: Continuously from signing of informed consent to 28 days after the last dose. Study to last for ~3 years. ]
6. Trough (Cmin) level rucaparib concentrations [ Time Frame: Cycle 1 Day 15, Cycle 2 Day 15, Cycle 3 Day 1, and Cycle 4 Day 1. Study to last for ~3 years. ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, California

Cedars Sinai Medical Center

Los Angeles, California, United States, 90048

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55902

United States, New York

New York University

New York, New York, United States, 10012

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

United States, Texas

MD Anderson Cancer Center

Houston, Texas, United States, 77030

Israel

Rambam Healthcare Campus

Haifa, Israel, 31096

Hadassah Hebrew University Hospital (Sharett Institute of Oncology)

Jerusalem, Israel, 91120

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel, 64239

Sponsors and Collaborators

Clovis Oncology, Inc.

Investigators

• Study Director: Heidi Giordano; Clovis Oncology, Inc.

More Information

• Responsible Party: Clovis Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT02042378
• Other Study ID Numbers: CO-338-023
• First Posted: January 22, 2014
• Last Update Posted: January 27, 2020
• Last Verified: January 2020

Keywords provided by Clovis Oncology, Inc.:

BRCA; BRCA mutation; germline BRCA; somatic BRCA; PARP inhibitor; rucaparib; CO-338; PF 01367338; AG 14699; Clovis; Clovis Oncology; RucaPanc

Additional relevant MeSH terms:

Pancreatic Neoplasms; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Rucaparib; Poly(ADP-ribose) Polymerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents