A Study of ABT-165 Plus FOLFIRI vs Bevacizumab Plus FOLFIRI in Subjects With Metastatic Colorectal Cancer Previously Treated With Fluoropyrimidine, Oxaliplatin and Bevacizumab

Study Overview
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Brief Summary
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A study to evaluate the efficacy and tolerability of ABT-165 plus FOLFIRI compared to bevacizumab plus FOLFIRI in participants with previously treated metastatic adenocarcinoma of the colon or rectum.

Official Title
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Phase 2 Study Comparing Efficacy and Safety of ABT-165 Plus FOLFIRI vs Bevacizumab Plus FOLFIRI in Metastatic Colorectal Cancer Previously Treated With Fluoropyrimidine, Oxaliplatin and Bevacizumab

Conditions
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Cancer

Intervention / Treatment
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* Drug: Leucovorin
* Drug: Fluorouracil - bolus
* Drug: Bevacizumab
* Drug: Fluorouracil - infusion
* Drug: ABT-165
* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum. Primary tumor has been resected > 3 months prior to randomization. At least 1 lesion on a computed tomography (CT) scan (preferred) or magnetic resonance imaging (MRI) that is measurable as defined by Response Evaluation Criteria In Solid Tumors (RECIST), Version 1.1. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1. Progression following treatment with fluoropyrimidine/oxaliplatin/bevacizumab-regimen in the metastatic setting. Adequate hematologic, renal and hepatic function. Exclusion Criteria: Any prior therapy with irinotecan Unresolved clinically significant toxicities from prior anticancer therapy, defined as any Common Terminology Criteria for Adverse Events (CTCAE) => Grade 2 Clinically significant conditions that increase the risk for antiangiogenic therapy. History of any of the following during first-line therapy with a bevacizumab-containing regimen: arterial thrombotic/thromboembolic event, bowel perforation, Grade 4 hypertension, Grade 3 proteinuria or Grade 3 - 4 bleeding event.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABT-165 plus FOLFIRI<br>ABT-165 plus FOLFIRI (irinotecan, leucovorin, fluorouracil). | Drug: Leucovorin<br>* Intravenous<br>* Other names: Folinic Acid;Drug: Fluorouracil - bolus<br>* Intravenous<br>* Other names: 5-FU;Drug: Fluorouracil - infusion<br>* Intravenous<br>* Other names: 5-FU;Drug: ABT-165<br>* Intravenous<br>Drug: Irinotecan<br>* Intravenous<br>* Other names: Irinotecan hydrochloride;|
| Active Comparator: Bevacizumab plus FOLFIRI<br>Bevacizumab plus FOLFIRI (irinotecan, leucovorin, fluorouracil). | Drug: Leucovorin<br>* Intravenous<br>* Other names: Folinic Acid;Drug: Fluorouracil - bolus<br>* Intravenous<br>* Other names: 5-FU;Drug: Bevacizumab<br>* Intravenous<br>* Other names: Avastin;Drug: Fluorouracil - infusion<br>* Intravenous<br>* Other names: 5-FU;Drug: Irinotecan<br>* Intravenous<br>* Other names: Irinotecan hydrochloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS is defined as the time from randomization until the first occurrence of radiographic progression determined by investigator assessment or death from any cause. | Follow up continued until the first occurrence of radiographic progression, death from any cause or termination of the study; median follow-up time was 25.6(0.3-64.4) and 37.6(0.3-66.3) weeks in ABT-165 plus FOLFIRI and Bevacizumab + FOLFIRI, respectively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is defined as the proportion of participants with a complete response (CR) or partial response (PR) as determined by a investigator assessment based on Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1. | From randomization up to 30 days after last dose of study drug; median time on follow-up was 25.6 (0.3 - 64.4) and 37.6 (0.3 - 66.3) weeks in ABT-165 plus FOLFIRI and Bevacizumab plus FOLFIRI, respectively | 
| Overall Survival (OS) | OS is defined as the time from randomization until death from any cause. | Follow up continued until the first occurrence of radiographic progression, death from any cause or termination of the study; median follow-up time was 25.6(0.3-64.4) and 37.6(0.3-66.3) weeks in ABT-165 plus FOLFIRI and Bevacizumab + FOLFIRI, respectively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer, colorectal cancer, ABT-165, FOLFIRI, Bevacizumab, bowel cancer, metastatic colorectal cancer, metastatic colorectal