Ph II Trial of a Novel Anti-angiogenic Agent in Combination With Chemotherapy for the Second-line Treatment of Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy of CT-322 comparative to bevacizumab, both in combination with irinotecan, 5-FU and leucovorin in the second-line treatment of subject with metastatic colorectal cancer

Official Title
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A Randomized, Double-Blind, Phase II Trial of CT-322 (BMS-844203) Plus Irinotecan, 5-FU and Leucovorin (FOLFIRI) Versus Bevacizumab Plus FOLFIRI as Second-Line Treatment for Metastatic Colorectal Cancer

Conditions
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Colorectal Cancer (CRC)

Intervention / Treatment
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* Drug: Irinotecan
* Drug: 5-Fluorouracil (bolus)
* Drug: 5-Fluorouracil (infusional)
* Drug: Leucovorin calcium
* Drug: CT-322
* Drug: Bevacizumab
* Drug: Bevacizumab Placebo (saline solution)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ECOG Performance Status (PS) ≤1 Histologically or cytologically confirmed, unresectable metastatic colorectal cancer Measurable disease by RECIST guidelines Evidence of disease progression following first-line therapy with a fluoropyrimidine, oxaliplatin, and bevacizumab (≤ 8 weeks since last dose) Available paraffin embedded tumor tissue Willing to give a whole blood sample for the study of proteins and genetic polymorphisms Exclusion Criteria: Less than 28 days elapsed since major surgery at time of randomization Known CNS metastases Excessive risk of bleeding (including use of therapeutic anticoagulation other than low dose aspirin) and history of thrombotic or embolic cerebrovascular accident Uncontrolled hypertension Clinically significant cardiovascular disease History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months Serious non-healing wound, active peptic ulcer, non-healing bone fracture, or bleeding skin metastasis Known HIV Positive

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1<br>Irinotecan/5-Fluorouracil (bolus)/5-Fluorouracil (infusional)/Leucovorin calcium/CT-322 | Drug: Irinotecan<br>* Solution, IV, 180 mg/m2, Q14 days, Until PD<br>* Other names: Camptosar;Drug: 5-Fluorouracil (bolus)<br>* Solution, IV, 400 mg/m2, Q14 days, Until PD<br>Drug: 5-Fluorouracil (infusional)<br>* Solution, IV, 2400 mg/m2, Q14 days, Until PD<br>Drug: Leucovorin calcium<br>* Solution, IV, 400 mg/m2, Q14 days, Until PD<br>Drug: CT-322<br>* Solution, IV, 2 mg/kg, Q7 days, Until PD<br>* Other names: BMS-844203;|
| Active Comparator: Arm 2<br>Irinotecan/5-Fluorouracil(bolus)/5-Fluorouracil(infusional)/Leucovorin calcium /Bevacizumab/Bevacizumab Placebo(saline solution) | Drug: Irinotecan<br>* Solution, IV, 180 mg/m2, Q14 days, Until PD<br>* Other names: Camptosar;Drug: 5-Fluorouracil (bolus)<br>* Solution, IV, 400 mg/m2, Q14 days, Until PD<br>Drug: 5-Fluorouracil (infusional)<br>* Solution, IV, 2400 mg/m2, Q14 days, Until PD<br>Drug: Leucovorin calcium<br>* Solution, IV, 400 mg/m2, Q14 days, Until PD<br>Drug: Bevacizumab<br>* Solutions, IV, 5 mg/kg, Q14 days, Until PD<br>* Other names: Avastin;Drug: Bevacizumab Placebo (saline solution)<br>* Solution, IV, 0 mg/kg, On day 8 of a 2-week cycle, Until PD<br>* Other names: Saline Solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival based on tumor assessments (CT/MRI) |  | Every 6 weeks until documented progressive disease, initiation fo subsequent therapy for colorectal cancer, or withdrawal of consent | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS), defined as the time the subject is randomized until death, in each arm |  | every 12 weeks | 
| Objective tumor response rate (ORR), defined as the proportion of randomized subjects in each arm whose best response is CR (complete response) or PR (partial response) using RECIST guidelines as determined by the site investigator |  | every 6 weeks | 
| Safety in the CT-322 plus irinotecan, 5-FU and leucovorin arm as measured by incidence of serious and non-serious adverse events, significant laboratory evaluations and significant physical examination findings in subjects |  | weekly |