A Study With Neoadjuvant mFOLFOX7 Plus Cetuximab to Determine the Surgical Conversion Rate for Unresectable Colorectal Cancer With Metastases Confined to the Liver
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|ClinicalTrials.gov Identifier: NCT00803647|
Recruitment Status : Completed
First Posted : December 5, 2008
Results First Posted : September 14, 2016
Last Update Posted : September 14, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Colorectal Cancer||Biological: cetuximab Drug: 5-FU Drug: oxaliplatin Drug: leucovorin||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||January 2010|
|Actual Primary Completion Date :||July 2013|
|Actual Study Completion Date :||November 2014|
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.
- 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 ]
- Reported Adverse Events. [ Time Frame: 8 months ]19 participants experienced at least one adverse event. There were a total of 95 adverse events reported. (Note: multiple occurrences of the same adverse event in one individual are counted only once.) Refer to the Adverse Events section for specifics. The Other Adverse Events section lists only those events occurring above 5% frequency.
- Overall Survival (OS). Time From Study Entry Until Death From Any Cause. [ Time Frame: 3 years ]
- 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 ]Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by PET/CT, CT scan, MRI or spiral CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective clinical Response Rate (cRR) = CR + PR during the 3 preoperative cycles, among the treated patients.
- Recurrence-free Survival (RFS). Time From Study Entry Until First Recurrence. [ Time Frame: 2 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00803647
Hide Study Locations
|United States, California|
|Loma Linda University Medical Center|
|Loma Linda, California, United States, 92354|
|St. Joseph Hospital|
|Orange, California, United States, 92868|
|Kaiser Permanente-San Diego|
|San Diego, California, United States, 92120|
|Kaiser Permanente Medical Center - Vallejo|
|Vallejo, California, United States, 94589|
|United States, Delaware|
|CCOP - Christiana Care Health Services|
|Newark, Delaware, United States, 19718|
|United States, Florida|
|M.D. Anderson Cancer Center - Orlando|
|Orlando, Florida, United States, 32806|
|United States, Illinois|
|CCOP - NorthShore University HealthSystem|
|Evanston, Illinois, United States, 60201|
|Naperville, Illinois, United States, 60566|
|United States, Iowa|
|University of Iowa|
|Iowa City, Iowa, United States, 52242|
|United States, Kentucky|
|Louisville, Kentucky, United States, 40202-5070|
|United States, Maryland|
|Franklin Square Hospital Center|
|Baltimore, Maryland, United States, 21237|
|United States, Michigan|
|Henry Ford Health System|
|Detroit, Michigan, United States, 48202|
|CCOP - Grand Rapids Clinical Oncology Program|
|Grand Rapids, Michigan, United States, 49503|
|CCOP, William Beaumont Hospital|
|Royal Oak, Michigan, United States, 48073|
|United States, Minnesota|
|CCOP - Metro-Minnesota|
|Saint Louis Park, Minnesota, United States, 55416|
|United States, Ohio|
|CCOP, Dayton, OH|
|Dayton, Ohio, United States, 45420|
|United States, Pennsylvania|
|Thomas Jefferson University Hospital|
|Philadelphia, Pennsylvania, United States, 19107|
|Allegheny Cancer Center at Allegheny General Hospital|
|Pittsburgh, Pennsylvania, United States, 15212|
|NSABP Foundation, Inc.|
|Pittsburgh, Pennsylvania, United States, 15212|
|University of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15232-1305|
|United States, South Carolina|
|CCOP - Upstate Carolina|
|Spartanburg, South Carolina, United States, 29303|
|United States, Vermont|
|Vermont Cancer Center at University of Vermont|
|Burlington, Vermont, United States, 05405-0075|
|United States, Wisconsin|
|Medical College of Wisconsin|
|Milwaukee, Wisconsin, United States, 53226|
|Principal Investigator:||Norman Wolmark, MD||NSABP Foundation Inc|