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

NCT01589419 | Completed Phase 1

• 1 other identifier: M12-950
• Study Type: interventional
• Target: 32
• Locations: 2 countries
• Sites: 6

Brief Summary

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).

Conditions

Locally Advanced Rectal Cancer

Keywords

DLT; radiation; veliparib; locally advanced rectal cancer; ABT-888; capecitabine; MTD; PARP

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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.

Study Arms (1)

veliparib and capecitabine and radiation

EXPERIMENTAL

Veliparib on days 1-7, capecitabine and radiation on days 1-5

Drug: veliparib; Drug: capecitabine; Radiation: radiation

Interventions

veliparib DRUG

see arm description

Also known as: ABT-888

veliparib and capecitabine and radiation

capecitabine DRUG

see arm description

Also known as: Xeloda

veliparib and capecitabine and radiation

radiation RADIATION

see arm description

veliparib and capecitabine and radiation

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Study Sites (6)

Site Reference ID/Investigator# 99095

Scottsdale, Arizona, 85258, United States

Location

Site Reference ID/Investigator# 68044

Chicago, Illinois, 60611, United States

Location

Site Reference ID/Investigator# 112395

Goshen, Indiana, 46526, United States

Location

Site Reference ID/Investigator# 68045

Durham, North Carolina, 27710, United States

Location

Site Reference ID/Investigator# 68043

Madison, Wisconsin, 53792, United States

Location

Site Reference ID/Investigator# 67882

East Melbourne, 3002, Australia

Location

Related Publications (1)

• 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.

  PMID: 28497757 RESULT

MeSH Terms

Interventions

veliparib; Capecitabine; Radiation

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Physical Phenomena

Study Officials

• Philip Komarnitsky, MD

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2012
• First Posted: May 2, 2012
• Study Start: June 1, 2012
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: November 20, 2017

Record last verified: 2015-01

Locations

AU (1); US (5)