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

AbbVie

Status and phase: Completed; Phase 2

Conditions: Untreated Metastatic Colorectal Cancer

Treatments: Drug: FOLFIRI; Drug: Veliparib; Drug: Fluorouracil infusion; Drug: Modified FOLFIRI; Drug: Placebo; Drug: Bevacizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02305758

M14-217

2014-002866-65 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 130 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum
• At least 1 unresectable lesion on a CT (Computerized Tomography) scan that is measurable as defined by Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1
• ECOG (Eastern Cooperative Oncology Group) performance score of 0 or 1
• Adequate hematologic, renal and hepatic function

Exclusion criteria

• Prior anti-cancer treatment for metastatic colorectal cancer
• Prior exposure to PARP (poly ADP-ribose polymerase) inhibitors
• The last course of adjuvant or neoadjuvant chemotherapy must have ended > 12 months prior to Cycle 1 Day -2
• Any clinically significant and uncontrolled major medical condition
• Participant is pregnant or lactating
• Any medical condition, which in the opinion of the study Investigator, places the participant at an unacceptably high risk for toxicities
• For those receiving bevacizumab, standard medical exclusionary conditions apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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130 participants in 2 patient groups, including a placebo group

Veliparib + modified FOLFIRI ± bevacizumab

Experimental group

Description:

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.

Treatment:

Drug: Bevacizumab

Drug: Veliparib

Drug: Fluorouracil infusion

Drug: Modified FOLFIRI

Placebo + FOLFIRI ± bevacizumab

Placebo Comparator group

Description:

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.

Treatment:

Drug: Bevacizumab

Drug: Placebo

Drug: FOLFIRI

Drug: Fluorouracil infusion