A Study With Neoadjuvant mFOLFOX7 Plus Cetuximab to Determine the Surgical Conversion Rate for Unresectable Colorectal Cancer With Metastases Confined to the Liver
FC-6 is a Phase II, multi-center clinical trial for patients with unresectable, wild-type K-RAS, colorectal cancer with metastases confined to the liver. Liver metastases must be determined by FC-6 criteria to be unresectable, and the colorectal cancer (CRC) tumor (primary or metastatic) must be found to be wild-type K-RAS. Patients with mutant K-RAS tumors are ineligible. K-RAS testing can be done through the local hospital or a tumor sample can be submitted to the FC-6 central lab (Esoterix Clinical Trial Services).
A primary aim of this study is to evaluate the surgical conversion rate using cytotoxic combination chemotherapy and biologic therapy with cetuximab, a monoclonal antibody targeted against the epidermal growth factor receptor. A second primary aim is to evaluate the safety and tolerability of a chemotherapy/targeted therapy regimen in this patient population. Secondary aims include determination of clinical response rate, recurrence-free survival for patients undergoing complete resection and/or ablation of liver metastases, and overall survival.
Metastatic Colorectal Cancer
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study to Determine the Surgical Conversion Rate in Patients Receiving Neoadjuvant mFOLFOX7 + Cetuximab for Unresectable Wild-Type K-RAS Colorectal Cancer With Metastases Confined to the Liver|
- The percentage of patients who had a curative (R0) liver metastasectomy following protocol treatment, i.e., metastatic disease that can be completely resected and/or ablated with no postoperative evidence of residual malignant disease (R0 resection). [ Time Frame: 8 months ] [ Designated as safety issue: No ]
- Reported adverse events. [ Time Frame: 8 months ] [ Designated as safety issue: Yes ]
- Overall Survival (OS). Time from study entry until death from any cause during the 2 years following study entry. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Objective clinical response rate (cRR). Measureable lesions that can be accurately measured in at least one dimension with conventional radiologic techniques or spiral CT. [ Time Frame: 8 months ] [ Designated as safety issue: No ]
- Recurrence-free survival (RFS). Time from study entry until first recurrence during the 2 years following study entry. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||January 2010|
|Estimated Study Completion Date:||January 2018|
|Estimated Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
mFOLFOX7 (5-FU, leucovorin, oxaliplatin) + cetuximab
500 mg/m2 IV every two weeks on days 1, 15, 29, and 43 of each 56 day cycle, for a total of 3 cycles. Cetuximab dose will be escalated by 100 mg/m2 every 2 weeks to a maximum dose of 800 mg/m2 if, at the time of retreatment, skin rash is less than or equal to grade 1, diarrhea is grade 0 (defined as less than or equal to 3 stools per day over baseline), and the patient is not experiencing any other greater than or equal to grade 2 toxicity attributed to cetuximab.
Other Name: ErbituxDrug: 5-FU
3000 mg/m2 IV continuous infusion over 46 hours every two weeks on days 1, 15, 29, and 43 of each 56 day cycle, for a total of 3 cycles.
Other Name: 5-fluorouracilDrug: oxaliplatin
85 mg/m2 IV every two weeks on days 1, 15, 29, and 43 of each 56 day cycle, for a total of 3 cycles.
Other Name: EloxatinDrug: leucovorin
400 mg/m2 IV every two weeks on days 1, 15, 29, and 43 of each 56 day cycle, for a total of 3 cycles.
All patients will receive the FC-6 study treatment regimen every 2 weeks during each 8-week cycle for a total of 3 cycles.
Baseline imaging of the chest, abdomen, and pelvis will be performed. CT scan or MRI of the abdomen will be performed after 1 cycle of neoadjuvant therapy to assess clinical response and resectability of liver metastases. If liver metastases are not deemed to be resectable at this assessment, but tumor assessment demonstrates stable disease or partial response, therapy will continue with re-assessment for clinical response and resectability after Cycle 2 and, if necessary, after Cycle 3.
After a minimum of 1 cycle of therapy, patients who meet the guidelines for resection of liver metastases will undergo liver metastasectomy (tumor resection and/or ablation) as soon as judged technically feasible by the hepatic surgeon in order to minimize chemotherapy damage to the liver and morbidity from surgery. At the investigator's discretion, the chemotherapy and cetuximab regimen may be continued for 1 additional treatment given at least 2 weeks before the planned date of surgery. This additional treatment, if given, will not be considered to be part of the 3 study therapy cycles.
The surgical goal is to perform a curative (R0) resection and/or ablation. If curative surgery was performed and if only 1 or 2 cycles of therapy were administered before surgery, postoperative therapy using the same regimen will resume 4-6 weeks following surgery to complete 3 cycles of study treatment. Following discontinuation of study therapy, all patients who undergo R0 resection (with or without ablation) will be followed every 3 months for the first 2 years on the study and then every 6 months for years 3 through 5.
Further therapy for patients who do not undergo R0 resection/ablation will be at the investigator's discretion. These patients will only be followed for vital status every 12 months for the remainder of the 5-year period following study entry.
A total sample size of 60 patients will be enrolled in the FC-6 trial.
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|Principal Investigator:||Norman Wolmark, MD||NSABP Foundation, Inc.|