Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Herbal and Botanical

Bevacizumab

Irinotecan

Leucovorin

Fluorouracil

Poly(ADP-ribose) Polymerase Inhibitors

Veliparib

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Enzyme Inhibitors

Cola

Dosing of oral veliparib (200 mg) began 2 days prior to the start of FOLFIRI and continued twice a day (BID) for a total of 7 consecutive days. At the discretion of the Investigator, bevacizumab (5 mg/kg) could be administered intravenously (IV) immediately preceding FOLFIRI. Modified FOLFIRI was administered as 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) immediately followed by fluorouracil 2400 mg/m\^2 (46-hour continuous infusion ± 4 hours) starting on Day 1 of each 14-day cycle.

Dosing of oral placebo (200 mg) began 2 days prior to the start of FOLFIRI and continued twice a day (BID) for a total of 7 consecutive days. At the discretion of the Investigator, bevacizumab (5 mg/kg) could be administered intravenously (IV) immediately preceding FOLFIRI. Standard FOLFIRI was administered as 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) immediately followed by fluorouracil 2400 mg/m\^2 (46-hour continuous infusion ± 4 hours) on Day 1 of each 14-day cycle.

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

Placebo

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

Modified FOLFIRI

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

FOLFIRI

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

Fluorouracil infusion

AbbVie Inc.

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.

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.

Study Comparing Veliparib Plus FOLFIRI Versus Placebo Plus FOLFIRI With or Without Bevacizumab in Previously Untreated Metastatic Colorectal Cancer

Randomized, Blinded, Multicenter, Phase 2 Study Comparing Veliparib Plus FOLFIRI ± Bevacizumab Versus Placebo Plus FOLFIRI ± Bevacizumab in Previously Untreated Metastatic Colorectal Cancer

PFS was defined as the number of days from the date the participant was randomized to the date the participant experienced an event of disease progression or death, whichever occurred first. All events of disease progression were included, whether the participant was still taking or had discontinued study drug. Events of death were included for participants who had not experienced an event of disease progression, if the death occurred within 8 weeks of the last evaluable disease progression assessment. If the participant did not have an event of disease progression and the participant had not died as defined above, data were censored at the date of the participant's last evaluable disease progression assessment. The PFS distribution was estimated using Kaplan-Meier methodology. Point estimates and 95% confidence intervals (95% CIs) for the PFS distribution quartiles are provided.

Overall survival was defined as the number of days from the date that the participant was randomized to the date of the participant's death. All events of death were included, regardless of whether the event occurred while the participant was still taking or had discontinued study drug. If a participant had not died, the data were censored at the date last known to be alive. The OS distribution was estimated using Kaplan-Meier methodology. Point estimates and 95% confidence intervals (95% CIs) for the OS distribution quartiles are provided.

ORR was defined as the proportion of participants with a complete (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) for target lesions, assessed by computed tomography (CT). Complete response (CR) was defined as disappearance of all target lesions; partial response (PR) ≥30% decrease in the the sum of diameters of target lesions, taking as reference the baseline sum diameters. For participants who underwent surgery, ORR was not evaluated after surgery.

AbbVie

TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of veliparib/placebo until 30 days after the last dose of veliparib/placebo and were collected whether elicited or spontaneously reported by the participant.

Veliparib + Modified FOLFIRI ± Bevacizumab

Placebo + FOLFIRI ± Bevacizumab

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Global Medical Services

Comparisons between treatment groups were performed using the Cox Proportional Hazard Model, stratified by planned bevacizumab use (planned use versus no planned use).

25th Quartile

50th Quartile

75th Quartile

Progression-Free Survival (PFS): Time to Event

Overall Survival (OS): Time to Event

Comparisons between treatment groups were performed using the Mantel-Haenszel method, stratified by planned bevacizumab use (planned use versus no planned use).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study Comparing Veliparib Plus FOLFIRI Versus Placebo Plus FOLFIRI With or Without Bevacizumab in Previously Untreated Metastatic Colorectal Cancer	NCT02305758	Untreated Metas...	Veliparib Placebo Modified FOLFIR... FOLFIRI Bevacizumab Fluorouracil in...	18 Years - 99 Years	AbbVie
Study Comparing Veliparib Plus FOLFIRI Versus Placebo Plus FOLFIRI With or Without Bevacizumab in Previously Untreated Metastatic Colorectal Cancer	NCT02305758	Untreated Metas...	Veliparib Placebo Modified FOLFIR... FOLFIRI Bevacizumab Fluorouracil in...	18 Years - 99 Years	AbbVie

Spots Global Cancer Trial Database for fluorouracil infusion