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

Sponsor

Cedars-Sinai Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT01908478

Collaborator

AbbVie (Industry)

Enrollment

Location

Arm

81.1

Actual Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer	Drug: Veliparib Drug: Gemcitabine Radiation: Intensity modulated radiation therapy	Phase 1

Detailed Description

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 Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 2, 2013

Actual Primary Completion Date :

Jul 14, 2017

Actual Study Completion Date :

Jul 6, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Combination: veliparib, gemcitabine, and IMRT	Drug: Veliparib Other Names: ABT-888 Drug: Gemcitabine Other Names: Gemzar Radiation: Intensity modulated radiation therapy

Arm

Intervention/Treatment

Experimental: Combination: veliparib, gemcitabine, and IMRT

Drug: Veliparib

Other Names:

ABT-888

Drug: Gemcitabine

Other Names:

Gemzar

Radiation: Intensity modulated radiation therapy

Outcome Measures

Primary Outcome Measures

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) [Days 1-70]

Secondary Outcome Measures

Assessment of objective response rates measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [From baseline to Week 26]
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
Evaluation of pre-treatment biopsy specimens for levels of various DNA repair proteins [Baseline only]
Change in PAR [Poly(ADP-ribosyl)ation] levels in peripheral blood mononuclear cells [Baseline, Weekly for 6 weeks, and at Weeks 10, 18, and 26]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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