Veliparib in Combination With Gemcitabine and Intensity Modulated Radiation Therapy in Patients With Pancreatic Cancer

Phase 1CompletedNCT01908478

Cedars-Sinai Medical Center34 enrolled

Overview

This is a Phase I Study of veliparib (ABT-888) in combination with Gemcitabine and Intensity Modulated Radiation Therapy in Patients with Locally Advanced, Unresectable Pancreatic Cancer. Primary Objectives: * Determine the maximum tolerable dose of veliparib in combination with gemcitabine and intensity modulated radiation therapy in patients with locally advanced pancreatic cancer. * Determine the safety and toxicity of the combination of veliparib with gemcitabine and radiation therapy in patients with locally advanced pancreatic cancer

Gemcitabine will be administered by intravenous infusion of 1000 mg/m2 over 30 minutes on days 1, 8, 15 of the cycle. Intensity modulated radiation therapy (IMRT) will be given to a total dose of 36 Gy in 15 fractions (2.4 Gy per fraction, one fraction per day, 5 fractions per week, Monday through Friday) beginning on day 1. Veliparib will be administered per a dose escalation schema. The starting dose of veliparib is 20 mg BID based upon safety/efficacy data available. Dose escalation will continue in 20 mg increments until the maximum tolerated dose (MTD) is reached. Intra-patient dose escalation will not be allowed.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Pancreatic Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients with histopathological or cytological diagnosis of adenocarcinoma of the pancreas, as well as those with high clinical suspicion of adenocarcinoma, which is deemed locally advanced unresectable or borderline resectable as determined by a pancreatic cancer surgeon and/or following evaluation by a GI oncology tumor board. * Age 18 years or older Exclusion Criteria: * Patients who have had prior anti-cancer treatment for their disease * Patients who are currently receiving any other investigational agents * Metastatic disease * History of allergic reactions attributed to compounds of similar chemical or biologic composition to PARP \[Poly (ADP-ribosome) polymerase\] inhibitors or gemcitabine * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Outcomes

Primary Outcomes

Maximum-tolerated dose (MTD) of veliparib based on the incidence of dose-limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)

Time frame: Days 1-70

Secondary Outcomes

Assessment of objective response rates measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response

Time frame: From baseline to Week 26

Evaluation of pre-treatment biopsy specimens for levels of various DNA repair proteins

Time frame: Baseline only

Change in PAR [Poly(ADP-ribosyl)ation] levels in peripheral blood mononuclear cells

Time frame: Baseline, Weekly for 6 weeks, and at Weeks 10, 18, and 26