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

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)

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).

Study Overview

• Status: Completed
• Conditions: Locally Advanced Rectal Cancer
• Intervention / Treatment: Drug: veliparib; Drug: capecitabine; Radiation: radiation

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • East Melbourne, Australia, 3002
    • Site Reference ID/Investigator# 67882
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Site Reference ID/Investigator# 99095
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Site Reference ID/Investigator# 68044
  • Indiana
    • Goshen, Indiana, United States, 46526
      • Site Reference ID/Investigator# 112395
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Site Reference ID/Investigator# 68045
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Site Reference ID/Investigator# 68043

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: veliparib and capecitabine and radiation; Veliparib on days 1-7, capecitabine and radiation on days 1-5	Drug: veliparib; see arm description; Other Names: ABT-888; Drug: capecitabine; see arm description; Other Names: Xeloda; Radiation: radiation; see arm description

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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.

Collaborators and Investigators

• Sponsor: AbbVie (prior sponsor, Abbott)

Publications and helpful links

General Publications

• Czito BG, Deming DA, Jameson GS, Mulcahy MF, Vaghefi H, Dudley MW, Holen KD, DeLuca A, Mittapalli RK, Munasinghe W, He L, Zalcberg JR, Ngan SY, Komarnitsky P, Michael M. Safety and tolerability of veliparib combined with capecitabine plus radiotherapy in patients with locally advanced rectal cancer: a phase 1b study. Lancet Gastroenterol Hepatol. 2017 Jun;2(6):418-426. doi: 10.1016/S2468-1253(17)30012-2. Epub 2017 Mar 27.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (ACTUAL): January 1, 2015
• Study Completion (ACTUAL): January 1, 2015

Study Registration Dates

• First Submitted: April 30, 2012
• First Submitted That Met QC Criteria: April 30, 2012
• First Posted (ESTIMATE): May 2, 2012

Study Record Updates

• Last Update Posted (ACTUAL): November 20, 2017
• Last Update Submitted That Met QC Criteria: November 16, 2017
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: capecitabine; veliparib; ABT-888; radiation; PARP; MTD; DLT; locally advanced rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Capecitabine; Veliparib
• Other Study ID Numbers: M12-950