A Study With Neoadjuvant mFOLFOX7 Plus Cetuximab to Determine the Surgical Conversion Rate for Unresectable Colorectal Cancer With Metastases Confined to the Liver

NCT ID: NCT00803647

Last Updated: 2021-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2014-11-30

Brief Summary

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.

Detailed Description

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.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

treatment

mFOLFOX7 (5-FU, leucovorin, oxaliplatin) + cetuximab

Group Type: EXPERIMENTAL

cetuximab

Intervention Type: BIOLOGICAL

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.

5-FU

Intervention Type: DRUG

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.

oxaliplatin

Intervention Type: DRUG

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.

leucovorin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: BIOLOGICAL

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Erbitux; 5-fluorouracil; Eloxatin

Eligibility Criteria

Inclusion Criteria

• The colorectal primary tumor or metastatic tumor must be determined to be wild-type K-RAS. The K-RAS test may have been performed through the local hospital, or a tumor sample may be submitted to the FC-6 central lab for K-RAS testing. If local K-RAS test results are reported as indeterminate, submission of a tumor sample for central testing is required. Note: Needle biopsy of liver metastasis is not recommended for the express purpose of obtaining tissue for K-RAS testing because of the risk of needle track dissemination of malignant cells.
• There must be documentation that the liver metastases must have been determined by a hepatic surgeon approved (by protocol defined criteria) to participate in FC-6 to be unresectable based on at least one of the following criteria: All of the liver metastases cannot be resected (and/or ablated) with negative margins, i.e., lesion(s) located in an area that would result in the resection of all of the hepatic veins or the main portal vein or the right and left hepatic arteries or the common bile duct; Complete resection and/or ablation would require greater than 60% of the liver parenchyma to be removed. Note: At the discretion of the hepatic surgeon, portal vein embolization (PVE) may be utilized preoperatively following neoadjuvant therapy to enhance the volume of the hepatic remnant. However, the determination of unresectability will be based on the estimate, at the time of study entry, of the percentage of liver parenchyma that would need to be removed. PVE may be employed preoperatively to enhance the overall safety, but not specifically the resectability of the liver metastasis(es).
• There must be documentation that: at least 3 of the 8 hepatic segments are free of metastases or; based on imaging studies, the patient is anticipated to have at least 40% of the liver will remain intact after surgery.
• If an adjuvant therapy regimen of 5-FU given alone or in combination with leucovorin, irinotecan, capecitabine, oxaliplatin, cetuximab, or bevacizumab was administered, the adjuvant therapy must have been discontinued more than 6 months prior to study entry.
• The patient must have had the following tests and exams within 4 weeks prior to study entry: medical history and physical exam; consultation with a hepatic surgeon approved for FC-6; and PET/CT scan or both a PET scan and a CT scan of the chest, abdomen, and pelvis must be performed. (MRI scan can be substituted for the CT scan.)
• There must be evidence of adequate bone marrow function: absolute neutrophil count (ANC) greater than or equal to 1500/mm3; Hemoglobin greater than or equal to 10 g/dL; Platelets greater than or equal to 100,000/mm3
• There must be evidence of adequate hepatic function: Total bilirubin less than or equal to upper limit of normal (ULN) for the lab; aspartate aminotransferase (AST) less than or equal to 5.0 x ULN for the lab
• Serum creatinine must be less than or equal to 1.5 mg/dL.

Conditions for patient ineligibility

• Diagnosis of anal or small bowel carcinoma.
• Colorectal cancers other than adenocarcinoma, e.g., sarcoma, lymphoma, carcinoid.
• Unresected primary tumor in the colon or rectum with significant symptoms related to obstruction or that will require radiation therapy.
• Evidence of extrahepatic metastases or non-contiguous extension of intrahepatic metastases to non-hepatic tissues.
• Radiographic evidence of metastases to portal lymph nodes (node greater than 1 cm in diameter) unless the node(s) are proven by biopsy to be negative.
• Previous hepatic resection and/or ablation, hepatic arterial infusion therapy, or any systemic therapy for metastatic disease. (Patients who have only had an excisional biopsy are eligible.)
• Radiation therapy to the liver.
• Pre-existing chronic hepatic disease (e.g., chronic active hepatitis, cirrhosis) that, in the opinion of the investigator and hepatic surgeon, would limit the patient's ability to undergo hepatic metastasectomy.
• Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 grade 3 or 4 anorexia or nausea related to metastatic disease.
• CTCAE v3.0 greater than or equal to grade 2 vomiting related to metastatic disease.
• CTCAE v3.0 greater than or equal to grade 2 sensory/motor neuropathy.
• Any of the following cardiac conditions: Documented congestive heart failure; Myocardial infarction within 6 months prior to study entry; Unstable angina within 6 months prior to study entry; Symptomatic arrhythmia.
• Serious or non-healing wound, skin ulcers, or bone fracture.
• History of bleeding diathesis or coagulopathy. (Patients on stable anticoagulant therapy are eligible.)
• Symptomatic interstitial lung disease or definitive evidence of interstitial lung disease described on CT scan, MRI, or chest x-ray in asymptomatic patients.
• Any evidence of active infection.
• Active inflammatory bowel disease.
• Other malignancies unless the patient is considered to be disease-free and has completed therapy for the malignancy greater than or equal to 12 months prior to study entry. Patients with the following cancers are eligible if diagnosed and treated within the past 12 months: carcinoma in situ of the cervix, colorectal carcinoma in situ, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
• Previous serious hypersensitivity reaction to monoclonal antibodies.
• Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.
• Pregnancy or lactation at the time of study entry. (WOCBP must have a negative pregnancy test within 2 weeks prior to study entry. Male and female patients of reproductive potential must agree to use adequate contraceptive methods during and for 2 months after study therapy. )
• Any other serious concomitant medical condition that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to participate in the study.
• Use of any investigational product within 30 days prior to study entry.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

NSABP Foundation Inc

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Norman Wolmark, MD

Role: PRINCIPAL_INVESTIGATOR

NSABP Foundation Inc

Locations

Loma Linda University Medical Center

Loma Linda, California, United States

St. Joseph Hospital

Orange, California, United States

Kaiser Permanente-San Diego

San Diego, California, United States

Kaiser Permanente Medical Center - Vallejo

Vallejo, California, United States

CCOP - Christiana Care Health Services

Newark, Delaware, United States

M.D. Anderson Cancer Center - Orlando

Orlando, Florida, United States

CCOP - NorthShore University HealthSystem

Evanston, Illinois, United States

Edward Hospital

Naperville, Illinois, United States

University of Iowa

Iowa City, Iowa, United States

NortonHealthcare, Inc.

Louisville, Kentucky, United States

Franklin Square Hospital Center

Baltimore, Maryland, United States

Henry Ford Health System

Detroit, Michigan, United States

CCOP - Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, United States

CCOP, William Beaumont Hospital

Royal Oak, Michigan, United States

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States

CCOP, Dayton, OH

Dayton, Ohio, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Allegheny Cancer Center at Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

NSABP Foundation, Inc.

Pittsburgh, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

CCOP - Upstate Carolina

Spartanburg, South Carolina, United States

Vermont Cancer Center at University of Vermont

Burlington, Vermont, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

NSABP FC-6

Identifier Type: -

Identifier Source: org_study_id