Study to Evaluate the Safety, Tolerability and Efficacy of FOLFOX + CT-011 Versus FOLFOX Alone

Study Overview
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Brief Summary
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This clinical trial will be performed in previously untreated patients with metastatic colorectal cancer. The study will evaluate the safety, tolerability and efficacy of the study drug, CT-011, in combination with FOLFOX chemotherapy (FOLFOX4 or mFOLFOX6) compared with treatment by FOLFOX alone.

Detailed Description
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The proposed clinical trial will be a multi-center, randomized, open label, active control study in previously untreated patients with metastatic colorectal cancer aimed to evaluate the safety, tolerability and efficacy of the monoclonal antibody, CT-011, administered at 3mg/kg in combination with FOLFOX chemotherapy (FOLFOX4 or mFOLFOX6) compared with treatment by FOLFOX alone. Approximately 168 patients are planned to be enrolled to this study.

Official Title
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Phase II Study to Evaluate the Safety, Tolerability and Efficacy of FOLFOX + CT-011 Versus FOLFOX Alone Administered Intravenously to Patients With Colorectal Adenocarcinoma Previously Untreated for Metastatic Disease

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: CT-011
* Drug: FOLFOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient's age is 18 years or older, both genders. Patients with metastatic disease who are eligible for first line FOLFOX chemotherapy. Adjuvant or neoadjuvant given at least 12 months prior for non-metastatic disease is permitted. ECOG performance status ≤ 1 At least 4 weeks from prior major surgery or radiotherapy. Life expectancy >3 months Hematology: ANC ≥ 1.5X109/L; Platelets >100x109/L. Adequate Renal function Adequate Hepatic functions Normal Cardiac function Exclusion Criteria: Patients who had adjuvant or neoadjuvant therapy for non-metastatic disease given within the last 12 months. Patients who had received Oxaliplatin within 12 months prior to diagnosis of metastatic disease. Patients on concurrent anti cancer therapy other than that allowed in the study. Patients on concurrent steroids, other than those allowed for routine antiemetics, or inhaled steroids Presence of clinically apparent or suspected brain metastasis. Patients who have had myocardial infarction, severe congestive heart failure, or significant arrhythmia within the past 6 months. Serious active infection at the time of pre-study screening. Active or history of autoimmune disorders/conditions. Women who are pregnant or lactating Concurrent active malignancy. Ascites, pleural effusions, or osteoblastic bone metastases as the only site of disease. Other prior malignancies, except for cured or adequately treated malignancies for which there has been no evidence of activity for more than 5 years. Subjects with a condition which may interfere with the subjects' ability to understand the requirements of the study. Patients with history of life threatening allergic reactions to food or drugs Patients with symptomatic peripheral neuropathy> Grade 1. Known positive HIV, Hepatitis B surface antigen or Hepatitis C antibody.

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: CT-011 in combination with FOLFOX<br>CT-011 (3 mg/kg) administered intravenously every 4 weeks for 4 weeks and every 12 weeks thereafter until disease progression or maximum tolerance. FOLFOX (FOLFOX4 or mFOLFOX6) administered 7 days after the first administration of CT-011 and repeated every 14 days for up to 24 cycles. At the end of FOLFOX therapy, patients who have not progressed will be eligible for maintenance chemotherapy with 5-FU/leucovorin at the same dose and schedule until disease progression or study drug discontinuation. | Drug: CT-011<br> <br> Drug: FOLFOX<br>* FOLFOX-4: each cycle consists of the following: oxaliplatin 85 mg/m2 on Day 1, leucovorin 200 mg/m2/day on Day 1 and Day 2 followed by 5-FU 400 mg/m2 bolus and a 22 hour infusion of 5-FU 600 mg/m2 for two consecutive days. mFOLFOX-6: each cycle consists of the following: oxaliplatin 85 mg/m2 and leucovorin 400 mg/m2 on Day 1, followed by 5-FU 400 mg/m2 bolus, followed by 5-FU 1200 mg/m2/day for two consecutive days (total 2,400 mg/m2 over 46-48 hours).<br>|
| Active Comparator: FOLFOX<br>FOLFOX (FOLFOX-4 or mFOLFOX6) administered every 14 days for up to 24 cycles. At the end of FOLFOX therapy, patients who have not progressed will be eligible for maintenance chemotherapy with 5-FU/leucovorin at the same dose and schedule until disease progression or study drug discontinuation. | Drug: FOLFOX<br>* FOLFOX-4: each cycle consists of the following: oxaliplatin 85 mg/m2 on Day 1, leucovorin 200 mg/m2/day on Day 1 and Day 2 followed by 5-FU 400 mg/m2 bolus and a 22 hour infusion of 5-FU 600 mg/m2 for two consecutive days. mFOLFOX-6: each cycle consists of the following: oxaliplatin 85 mg/m2 and leucovorin 400 mg/m2 on Day 1, followed by 5-FU 400 mg/m2 bolus, followed by 5-FU 1200 mg/m2/day for two consecutive days (total 2,400 mg/m2 over 46-48 hours).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint will be the median progression free survival in patients treated with CT-011 plus FOLFOX compared to that of patients treated with FOLFOX alone. |  | 32 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of safety, tolerability, pharmacokinetics and immunogenicity of CT-011. |  | 32 months | 
| Anti tumor activity of the antibody. |  | 32 months | 
| Objective response rate by RECIST. |  | 32 months | 
| Progression-free survival rates. |  | 32 months | 
| Response duration. |  | 32 months | 
| Overall survival. |  | 32 months | 
| Tumor and immunological markers. |  | 32 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic colorectal cancer, FOLFOX chemotherapy