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
Primary Purpose
Locally Advanced Rectal Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
veliparib
capecitabine
radiation
Sponsored by
About this trial
This is an interventional treatment trial for Locally Advanced Rectal Cancer focused on measuring DLT, radiation, veliparib, locally advanced rectal cancer, ABT-888, capecitabine, MTD, PARP
Eligibility Criteria
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
Sites / Locations
- Site Reference ID/Investigator# 99095
- Site Reference ID/Investigator# 68044
- Site Reference ID/Investigator# 112395
- Site Reference ID/Investigator# 68045
- Site Reference ID/Investigator# 68043
- Site Reference ID/Investigator# 67882
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
veliparib and capecitabine and radiation
Arm Description
Veliparib on days 1-7, capecitabine and radiation on days 1-5
Outcomes
Primary Outcome Measures
Determine the maximum tolerated dose (MTD) and/or establish the recommended phase two dose (RPTD)
Secondary Outcome Measures
Assess the safety (number of participants with adverse events and types of adverse events observed)
Assess the tolerability (number of participants with adverse events and types of adverse events observed)
Assess the pharmacokinetic profile by area under the curve vs. dose of veliparib
Full Information
NCT ID
NCT01589419
First Posted
April 30, 2012
Last Updated
November 16, 2017
Sponsor
AbbVie (prior sponsor, Abbott)
1. Study Identification
Unique Protocol Identification Number
NCT01589419
Brief Title
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
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2015
Overall Recruitment Status
Completed
Study Start Date
June 2012 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
January 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie (prior sponsor, Abbott)
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Rectal Cancer
Keywords
DLT, radiation, veliparib, locally advanced rectal cancer, ABT-888, capecitabine, MTD, PARP
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
veliparib and capecitabine and radiation
Arm Type
Experimental
Arm Description
Veliparib on days 1-7, capecitabine and radiation on days 1-5
Intervention Type
Drug
Intervention Name(s)
veliparib
Other Intervention Name(s)
ABT-888
Intervention Description
see arm description
Intervention Type
Drug
Intervention Name(s)
capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
see arm description
Intervention Type
Radiation
Intervention Name(s)
radiation
Intervention Description
see arm description
Primary Outcome Measure Information:
Title
Determine the maximum tolerated dose (MTD) and/or establish the recommended phase two dose (RPTD)
Time Frame
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 Measure Information:
Title
Assess the safety (number of participants with adverse events and types of adverse events observed)
Time Frame
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.
Title
Assess the tolerability (number of participants with adverse events and types of adverse events observed)
Time Frame
From first study drug dose and ongoing at each weekly treatment visit, through completion of dosing period (anticipated to be approximately 5 weeks).
Title
Assess the pharmacokinetic profile by area under the curve vs. dose of veliparib
Time Frame
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philip Komarnitsky, MD
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
Site Reference ID/Investigator# 99095
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Site Reference ID/Investigator# 68044
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Site Reference ID/Investigator# 112395
City
Goshen
State/Province
Indiana
ZIP/Postal Code
46526
Country
United States
Facility Name
Site Reference ID/Investigator# 68045
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Site Reference ID/Investigator# 68043
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Site Reference ID/Investigator# 67882
City
East Melbourne
ZIP/Postal Code
3002
Country
Australia
12. IPD Sharing Statement
Citations:
PubMed Identifier
28497757
Citation
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.
Results Reference
result
Learn more about this trial
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
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