Phase II Trial of Neoadjuvant FOLFOX4 and Cetuximab for Localized Adenocarcinoma of Rectum

Study Overview
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Brief Summary
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This study involves the use of Oxaliplatin, 5-Fluorouracil (5-FU), Leucovorin and Cetuximab, which are all medicines approved by the Food and Drug Administration (FDA) and are commercially available. This treatment regimen will possibly be combined with radiation before and/or after surgery depending on your response to the treatment. Their use in this exact combination is considered experimental. The purpose of this study is to find out how effective this combination of chemotherapy is as treatment for rectal cancer that has not spread to other parts of the body. The side effects and survival experienced by subjects receiving these drugs will also be evaluated. This is a phase II research study.

Detailed Description
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Primary Objective: - Down-staging of the tumor Secondary Objectives: Pathologic response rate Tumor marker response Incidence of sphincter sparing surgery Progression-free survival Overall Survival

Official Title
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A Phase II Trial of Neoadjuvant FOLFOX4 and Cetuximab for Localized Adenocarcinoma of the Rectum

Conditions
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Rectal Cancer

Intervention / Treatment
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* Drug: FOLFOX4
* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients must have newly diagnosed, histologically proven adenocarcinoma of the rectum. Locally advanced T3, T4 or any T with N1, N2, staged by trans-rectal ultrasound. All patients must have an abdominal/pelvis CT scan or MRI confirming no evidence of distant metastases. Patients must have an ECOG PS ≤ 2 Patient has signed informed consent Lower Age Limit: 18 years Upper Age Limit: No upper age limit Laboratory parameters: Hgb: > 9.0 g/dl ANC >1500/ul Platelet >100,000/ul Creatinine < 2x ULN Bilirubin < 2x ULN ALT < 2x ULN Exclusion Criteria: Administration of any prior systemic anticancer therapy for colorectal cancer (eg, chemotherapy, antibody therapy, immunotherapy, gene therapy, vaccine therapy, cytokine therapy, angiogenesis inhibitors). Previous intra-arterial cytotoxic chemotherapy given as treatment for colorectal cancer. Previous pelvic radiotherapy. Known allergy or intolerance to oxaliplatin, 5-FU, cetuximab or leucovorin. Pregnant or breast-feeding women: female patients must agree to use effective contraception, must be surgically sterile, or must be postmenopausal. Male patients must agree to use effective contraception or be surgically sterile. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. All at-risk female patients must have a negative serum pregnancy test within 7 days prior to registration. Active inflammatory bowel disease, significant bowel obstruction, or chronic diarrhea (grade 2). Myocardial infarction or stroke within the previous 6 months, or ongoing unstable angina, symptomatic congestive heart failure, or serious uncontrolled cardiac dysrhythmia. Known human immunodeficiency virus (HIV) positivity or acquired-immunodeficiency-syndrome (AIDS)-related illness. No previous or concurrent malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer for which the patient has been disease-free for 3 years. Known CNS metastases Preexisting neuropathy > Grade 2 Prior therapy which specifically and directly targets the EGFR pathway Prior severe infusion reaction to a monoclonal antibody Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure and cardiomyopathy with decreased ejection fraction.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>FOLFOX4 + Cetuximab | Drug: FOLFOX4<br>* oxaliplatin (85mg/m2 on days 1 and 15 of each cycle)+ 5FU Bolus (400mg/m2 on days 1, 2, 15, and 16 of each cycle) + 5FU CI (600mg/m2 on days 1, 2, 15, and 16 of each cycle) + Leucovorin (200mg/m2 on days 1, 2, 15, and 16 of each cycle)<br>* Other names: Oxaliplatin (Eloxatin), 5FU (5-Fluorouracil) and Leucovorin (Folinic Acid);Drug: Cetuximab<br>* Cetuximab 400mg/m2 on day 1 only, 250mg/mr on days 8, 15, and 22 of each cycle.<br>* Other names: Cetuximab (C225, Erbitux);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Down-staging of the Tumor; Response to Therapy | Down-staging of the tumor and tumor response rate is defined as the proportion of participant who have any evidence of complete response (CR), pathologic complete response (pCR), or partial response (PR). | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Number of participants who achieve progression free survival, defined as the time from date of registration to date of disease progression, up through study closure. Progressive disease is defined as ≥ 20% increase in the sum of the longest dimensions of the primary lesion taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of 1 or more new lesions. | Up to 3 years | 
| Overall Survival | Overall survival is defined as the time from date of registration to date of death. In the absence of confirmation of death, survival time will be censored at the last date of follow-up. | Up to 3 years |