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

NCT00803647 | Completed Phase 2 Results

• 1 other identifier: NSABP FC-6
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 23

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.

Conditions

Metastatic Colorectal Cancer

Keywords

NSABP; Cetuximab; FOLFOX7; Oxaliplatin; Leucovorin; 5-FU; colorectal cancer; KRAS wild type; metastatic colorectal cancer; Erbitux; Eloxatin; Liver resection; Liver ablation; Metastasectomy

Outcome Measures

Primary Outcomes (2)

• 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).

  8 months

• Reported Adverse Events.

  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.

  8 months

Secondary Outcomes (3)

• Overall Survival (OS). Time From Study Entry Until Death From Any Cause.

  18 months

• Objective Clinical Response Rate (cRR). Measureable Lesions That Can be Accurately Measured in at Least One Dimension With Conventional Radiologic Techniques or Spiral CT.

  8 months

• Recurrence-free Survival (RFS). Time From Study Entry Until First Recurrence.

  2 years

Study Arms (1)

treatment

EXPERIMENTAL

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

Biological: cetuximab; Drug: 5-FU; Drug: oxaliplatin; Drug: leucovorin

Interventions

cetuximab 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.

Also known as: Erbitux

treatment

5-FU 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.

Also known as: 5-fluorouracil

treatment

oxaliplatin 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.

Also known as: Eloxatin

treatment

leucovorin 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.

treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Conditions for patient eligibility * Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and must be considered a potential candidate for a major hepatic surgical procedure. * The patient must have histologic or cytologic confirmation of a diagnosis of colorectal adenocarcinoma. * There must be documentation by PET/CT scan, CT scan, MRI, or intraoperative palpation (at the time of resection of the primary colorectal tumor, if applicable) that the patient has evidence of hepatic metastasis. (Histologic confirmation of hepatic metastasis is not required.) * Patients are eligible with any of the following: primary tumor and regional nodes resected with clear surgical margins and no evidence of extrahepatic disease or; unresected primary tumor with plans to resect the primary tumor prior to study entry or; unresected primary tumor with plans to resect the primary tumor and the liver metastases in a single surgical procedure performed within 2-7 weeks after the last preoperative dose of chemotherapy/cetuximab or; unresected primary with plans to resect the primary tumor and the liver metastases in staged procedures performed within 2-7 weeks after the last preoperative dose of chemotherapy/cetuximab. * 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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• NSABP Foundation Inc: lead
• Bristol-Myers Squibb: collaborator

Study Sites (23)

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

St. Joseph Hospital

Orange, California, 92868, United States

Location

Kaiser Permanente-San Diego

San Diego, California, 92120, United States

Location

Kaiser Permanente Medical Center - Vallejo

Vallejo, California, 94589, United States

Location

CCOP - Christiana Care Health Services

Newark, Delaware, 19718, United States

Location

M.D. Anderson Cancer Center - Orlando

Orlando, Florida, 32806, United States

Location

CCOP - NorthShore University HealthSystem

Evanston, Illinois, 60201, United States

Location

Edward Hospital

Naperville, Illinois, 60566, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

NortonHealthcare, Inc.

Louisville, Kentucky, 40202-5070, United States

Location

Franklin Square Hospital Center

Baltimore, Maryland, 21237, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

CCOP - Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, 49503, United States

Location

CCOP, William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, 55416, United States

Location

CCOP, Dayton, OH

Dayton, Ohio, 45420, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Allegheny Cancer Center at Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

NSABP Foundation, Inc.

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232-1305, United States

Location

CCOP - Upstate Carolina

Spartanburg, South Carolina, 29303, United States

Location

Vermont Cancer Center at University of Vermont

Burlington, Vermont, 05405-0075, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Fluorouracil; Oxaliplatin; Leucovorin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Results Point of Contact

• Title: Diana Gosik, Director Department of Site and Study Management
• Organization: NSABP Foundation

diana.gosik@nsabp.org

412-339-5333

Study Officials

• Norman Wolmark, MD

  NSABP Foundation Inc

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2008
• First Posted: December 5, 2008
• Study Start: January 1, 2010
• Primary Completion: July 1, 2013
• Study Completion: November 1, 2014
• Last Updated: October 6, 2021
• Results First Posted: September 14, 2016

Record last verified: 2021-10

Locations

US (23)