A Clinical Study Conducted in Multiple Centers Evaluating Escalating Doses of Veliparib in Combination With Capecitabine and Radiation in Patients With Locally Advanced Rectal Cancer

Study Overview
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Brief Summary
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An open-label, Phase 1b, dose escalation study evaluating the safety and tolerability of the PARP inhibitor Veliparib in combination with capecitabine and radiation in subjects with locally advanced rectal cancer (LARC).

Official Title
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An Open-Label Phase 1b Study of the Safety and Tolerability of Veliparib in Combination With Capecitabine and Radiation in Subjects With Locally Advanced Rectal Cancer (LARC)

Conditions
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Locally Advanced Rectal Cancer

Intervention / Treatment
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* Drug: veliparib
* Drug: capecitabine
* Radiation: radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be ≥ 18 years of age All subjects must have newly diagnosed, histologically proven adenocarcinoma of the rectum All subjects must have an abdominal/pelvis computed tomography (CT ) scan or magnetic resonance imaging (MRI) confirming no evidence of distant metastases Distal border of tumor < 12 cm from anal verge Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 to 2 No prior treatment for LARC however prior treatments for other cancers are acceptable as long as they are considered curative Exclusion Criteria: Subject is an unsuitable candidate for TME surgery Subject has received anticancer therapy Subject has received prior radiation therapy Subject has had major surgery within 28 days prior to the first dose of study drug History of gastric surgery, vagotomy, bowel resection or any surgical procedure that might interfere with gastrointestinal motility, pH or absorption

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: veliparib and capecitabine and radiation<br>Veliparib on days 1-7, capecitabine and radiation on days 1-5 | Drug: veliparib<br>* see arm description<br>* Other names: ABT-888;Drug: capecitabine<br>* see arm description<br>* Other names: Xeloda;Radiation: radiation<br>* see arm description<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the maximum tolerated dose (MTD) and/or establish the recommended phase two dose (RPTD) |  | From first study drug dose and at each weekly treatment visit until dose-limiting toxicities (DLT) observed or completion of dosing period (anticipated to be approximately 5 weeks). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the safety (number of participants with adverse events and types of adverse events observed) |  | From screening and ongoing at each weekly treatment visit through dosing period (anticipated to be approximately 5 weeks), prior to surgery and at the final visit. | 
| Assess the tolerability (number of participants with adverse events and types of adverse events observed) |  | From first study drug dose and ongoing at each weekly treatment visit, through completion of dosing period (anticipated to be approximately 5 weeks). | 
| Assess the pharmacokinetic profile by area under the curve vs. dose of veliparib |  | Multiple measurements over time points (0, .5, 1, 2, 3, 4, 6 hours post dose) Day 1, Day 2 and at the pre-dose time point on Day 5 and week 2 visit. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DLT, radiation, veliparib, locally advanced rectal cancer, ABT-888, capecitabine, MTD, PARP