Clinical trial NCT01589419: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Locally Advanced Rectal Cancer
Keywords: DLT
radiation
veliparib
locally advanced rectal cancer
ABT-888
capecitabine
MTD
PARP
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2012-05-02
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Determine the maximum tolerated dose (MTD) and/or establish the recommended phase two dose (RPTD)
timeFrame: 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:
measure: Assess the safety (number of participants with adverse events and types of adverse events observed)
timeFrame: 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.
measure: Assess the tolerability (number of participants with adverse events and types of adverse events observed)
timeFrame: From first study drug dose and ongoing at each weekly treatment visit, through completion of dosing period (anticipated to be approximately 5 weeks).
measure: Assess the pharmacokinetic profile by area under the curve vs. dose of veliparib
timeFrame: 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.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Site Reference ID/Investigator# 99095
state: Arizona
city: Chicago
country: United States
facility: Site Reference ID/Investigator# 68044
state: Illinois
city: Goshen
country: United States
facility: Site Reference ID/Investigator# 112395
state: Indiana
city: Durham
country: United States
facility: Site Reference ID/Investigator# 68045
state: North Carolina
city: Madison
country: United States
facility: Site Reference ID/Investigator# 68043
state: Wisconsin
city: East Melbourne
country: Australia
facility: Site Reference ID/Investigator# 67882
Study officials:
affiliation: AbbVie
name: Philip Komarnitsky, MD
role: STUDY_DIRECTOR
References:
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.