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

NCT02305758 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: M14-2172014-002866-65
• Study Type: interventional
• Target: 130
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Untreated Metastatic Colorectal Cancer

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

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS): Time to Event

  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.

  Every 8 weeks from Cycle 1, Day 1 until radiographic progression was observed. The maximum observed follow up duration at the progression-free survival analysis time was 579 days.

Secondary Outcomes (2)

• Overall Survival (OS): Time to Event

  Survival information was to be collected 4 wks after the last study visit, continuing every 4 wks for 1 yr, then every 8 wks for up to 2 more yrs or until death. The maximum observed follow up duration at the overall survival analysis time was 914 days.

• Objective Response Rate (ORR)

  Per protocol, post-baseline tumor assessment was conducted every 8 weeks from Cycle 1 Day 1 until radiographic progression. The maximum observed follow up duration at the progression-free survival analysis time was 579 days.

Study Arms (2)

Veliparib + modified FOLFIRI ± bevacizumab

EXPERIMENTAL

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.

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

Placebo + FOLFIRI ± bevacizumab

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: FOLFIRI; Drug: Bevacizumab; Drug: Fluorouracil infusion

Interventions

Veliparib DRUG

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

Also known as: ABT-888

Veliparib + modified FOLFIRI ± bevacizumab

Placebo DRUG

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 + FOLFIRI ± bevacizumab

Modified FOLFIRI DRUG

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

Veliparib + modified FOLFIRI ± bevacizumab

FOLFIRI DRUG

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

Placebo + FOLFIRI ± bevacizumab

Bevacizumab DRUG

At the discretion of the Investigator, 5 mg/kg may be administered intravenously immediately preceding FOLFIRI dosing

Also known as: Avastin

Placebo + FOLFIRI ± bevacizumab; Veliparib + modified FOLFIRI ± bevacizumab

Fluorouracil infusion DRUG

2400 mg/m\^2 (46-hour continuous infusion ± 4 hours) starting on Day 1 of each 14-day cycle

Also known as: 5-FU

Placebo + FOLFIRI ± bevacizumab; Veliparib + modified FOLFIRI ± bevacizumab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AbbVie: lead

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

veliparib; IFL protocol; Bevacizumab; Fluorouracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2014
• First Posted: December 3, 2014
• Study Start: December 2, 2014
• Primary Completion: September 22, 2017
• Study Completion: September 22, 2017
• Last Updated: November 20, 2018
• Results First Posted: November 20, 2018

Record last verified: 2018-11