Locally Advanced Rectal Cancer
Conditions
Keywords
DLT, radiation, veliparib, locally advanced rectal cancer, ABT-888, capecitabine, MTD, PARP
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).
Interventions
DRUGveliparib
see arm description
DRUGcapecitabine
see arm description
RADIATIONradiation
see arm description
Sponsors
AbbVie (prior sponsor, Abbott)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| 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. |
Countries
Australia, United States
Outcome results
None listed