Study Comparing Veliparib Plus FOLFIRI Versus Placebo Plus FOLFIRI With or Without Bevacizumab in Previously Untreated Metastatic Colorectal Cancer
Condition: Untreated Metastatic Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      This was a blinded, randomized, placebo-controlled Phase 2 multicenter study evaluating the
      efficacy and tolerability of veliparib plus irinotecan, fluorouracil, and leucovorin
      chemotherapy regimen (FOLFIRI) compared to placebo plus FOLFIRI in participants with
      previously untreated metastatic colorectal cancer. Participants could also have been treated
      with bevacizumab at the discretion of the Investigator.
    

Detailed description: 
      Participants were randomized to one of 2 groups: veliparib plus FOLFIRI ± bevacizumab
      (veliparib group) or placebo plus FOLFIRI ± bevacizumab (placebo group), and stratified by
      planned use of bevacizumab (planned bevacizumab use compared to unplanned use of bevacizumab)
      and regions of the world (North America versus rest of world). In this study, the term
      FOLFIRI was used to describe both the standard regimen containing a fluorouracil bolus that
      was administered to participants randomized to the placebo arm, and a modified regimen with a
      saline bolus that was administered to participants randomized to the veliparib arm. One cycle
      of protocol therapy consisted of 14 days, defined as Day -2 through Day 12. Dosing of oral
      veliparib/placebo began 2 days prior to the start of FOLFIRI and continued twice a day for a
      total of 7 consecutive days. At the discretion of the Investigator, bevacizumab could be
      administered intravenously immediately preceding FOLFIRI. Study visits were conducted on Day
      1 and Day 8 of the first and second cycles, then on Day 1 of each subsequent cycle.
      Participants were to continue protocol therapy and study visits until they met one of the
      defined discontinuation criteria. When the Investigator determined that a participant met the
      criteria for discontinuation, a final visit was conducted. Participants were to have had one
      follow-up visit approximately 30 days after the last dose of protocol therapy. Sites began
      collecting post-treatment and survival information 4 weeks after the last clinical
      assessment. Post-baseline radiographic tumor assessment was to be conducted every 8 weeks
      from Cycle 1, Day 1 (prior to the start of a new cycle) until radiographic progression.
    

Intervention name(s): Veliparib; Placebo; Modified FOLFIRI; FOLFIRI; Bevacizumab; Fluorouracil infusion
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): 200 mg oral dose beginning 2 days prior to the start of FOLFIRI and continuing twice a day (BID) for a total of 7 consecutive days; 200 mg oral dose beginning 2 days prior to the start of FOLFIRI and continuing twice a day (BID) for a total of 7 consecutive days; Irinotecan 180 mg/m^2 (90-minute infusion ± 30 minutes); leucovorin 400 mg/m^2 (90-minute infusion ± 30 minutes); and saline bolus (up to 15-minute infusion) on Day 1 of each 14-day cycle; Irinotecan 180 mg/m^2 (90-minute infusion ± 30 minutes); leucovorin 400 mg/m^2 (90-minute infusion ± 30 minutes); and fluorouracil bolus 400 mg/m^2 (up to 15-minute infusion) on Day 1 of each 14-day cycle; At the discretion of the Investigator, 5 mg/kg may be administered intravenously immediately preceding FOLFIRI dosing; 2400 mg/m^2 (46-hour continuous infusion ± 4 hours) starting on Day 1 of each 14-day cycle
Other intervention name(s): ABT-888; Avastin; 5-FU
Intervention MeSH terms: Bevacizumab; Fluorouracil; Veliparib
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: PARP inhibitor; veliparib; metastatic colorectal cancer; ABT-888; first line; previously untreated; colorectal cancer; colon cancer; rectal cancer; FOLFIRI; fluorouracil; 5-FU; leucovorin; irinotecan