Colorectal Cancer RECHALLENGE

Study Overview
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Brief Summary
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Primary Objective: To demonstrate that re-challenge with an oxaliplatin based regimen (modified FOLFOX-6) will provide a clinical disease control rate (DCR) of at least 20% at the end of the chemotherapy. Secondary Objective: To evaluate other measures of tumour's responses and safety.

Official Title
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A Phase II Study of Modified FOLFOX-6 Chemotherapy as First-line Treatment of Metastatic Colorectal Cancer in Patients Who Have Received Oxaliplatin-based Adjuvant Chemotherapy

Conditions
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Colorectal Neoplasms

Intervention / Treatment
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* Drug: OXALIPLATIN (SR96669)
* Drug: 5-FLUOROURACIL (5-FU)
* Drug: LEUCOVORIN (LV)
* Drug: BEVACIZUMAB


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Histologically proven adenocarcinoma of colon or rectum Measurable metastatic disease, either inoperable, or residual after surgical procedure No prior chemotherapy for metastatic disease For colon cancer: prior adjuvant chemotherapy with oxaliplatin that ended at least 12 months prior to enrollment. For rectal cancer: at least 12 months since prior use of oxaliplatin in neoadjuvant or adjuvant chemotherapy Adequate liver and kidney function: Total bilirubin inferior to 1.5 ULN Serum Creatinine inferior to 150 umol/L Creatinine clearance (ClCr) > 30 mL/min ALT / AST inferior to 3 ULN Adequate hematological function Neutrophils > or equal 1.5 x 109/L Platelets > or equal 100 x 109/L Exclusion criteria: Metastatic disease presenting without prior adjuvant chemotherapy Metastatic disease presenting after non-oxaliplatin-containing adjuvant chemotherapy Peripheral sensory or motor neuropathy > grade 1 Eastern Cooperative Oncology Group (ECOG) Performance status > 2 Other active malignancy History of known allergy to oxaliplatin or other platinum compounds, to 5-FU, to Leucovorin or to any ingredients in the formulations or the containers Patients who are pregnant, or breast-feeding Patients with severe renal impairment (ClCr < 30 mL/min) Pernicious anemia or other megaloblastic anemia with Vitamin B12 deficiency Patients with reproductive potential not implementing accepted and effective method of contraception (the definition of effective method of contraception will be based on the investigators' judgment) Participation in another clinical trial with any investigational drug within 30 days prior to study screening For patient who will receive Bevacizumab: Bevacizumab is contraindicated in patients with know hypersensitivity to any components of the product and to Chinese hamster ovary cell product or other recombinant human or humanized antibodies Presence of any symptoms suggesting brain metastasis The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Patients will receive modified FOLFOX-6 regimen: oxaliplatin 85mg/m2, day 1 (given as a 2-hour infusion) LV 400mg/m2, day 1 (given as a 2-hour infusion simultaneous to oxaliplatin) 5-FU given as a bolus IV 400mg/m2 dose on day 1 followed by 2400mg/m2 continuous infusion over 46 hours (day 1 and 2) A cycle is defined as 2 weeks. Patients will receive cycles of modified FOLFOX-6 regimen every 2 weeks up to a maximum of 8 cycles. Use of bevacizumab is at the discretion of the treating physician. | Drug: OXALIPLATIN (SR96669)<br>* Pharmaceutical form: Lyophilized powder for injection (50mg/vial or 100mg/vial) or aqueous solution (50mg/10mL or 100mg/20mL) Route of administration: IV<br>Drug: 5-FLUOROURACIL (5-FU)<br>* Pharmaceutical form: vials of 5g/100mL (50mg/mL) Route of administration: IV<br>Drug: LEUCOVORIN (LV)<br>* Pharmaceutical form: vials of 50mg/5mL or 500mg/50mL (10mg/mL) Route of administration: IV<br>Drug: BEVACIZUMAB<br>* Pharmaceutical form: vials of 100mg/4mL or 400mg/16mL (25mg/mL) Route of administration: IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary endpoint for the first thirteen patients according to the Simons Design: Clinical DCR (Disease Control Rate) at the end of stage I, based on Response Evaluation Criteria on Solid Tumors (RECIST) criteria. |  | At the end of 8 cycles or end of treatment which occurs first. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) |  | evaluated at 10 weeks, 16 weeks and 40 weeks | 
| Duration of response |  | evaluated at 10 weeks, 16 weeks and 40 weeks | 
| Adverse events |  | At each visit, i.e. every two weeks | 
| Overall response rate of stage I and II |  | evaluated at week 14 |