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

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