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

Pancreatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02042378
• Other study ID #: CO-338-023
• Status: Completed
• Phase: Phase 2
• Start date: April 2014
• Est. completion date: May 2016

Study information

• Verified date: June 2023
• Source: zr Pharma & GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: May 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Ductal Adenocarcinoma
• Pancreatic Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Israel	Rambam Healthcare Campus	Haifa
Israel	Hadassah Hebrew University Hospital (Sharett Institute of Oncology)	Jerusalem
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
United States	MD Anderson Cancer Center	Houston	Texas
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	New York University	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
zr Pharma & GmbH

Countries where clinical trial is conducted

United States,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.