Study of Cetuximab in Combination With mFOLFOX-6 (Oxaliplatin, Leucovorin, 5-FU) to Treat Colorectal Liver Metastatic Cancer Patients (CLIME)

Open-label, Uncontrolled, Multi-center, Phase II Study of Cetuximab in Combination With mFOLFOX-6 as First-line Treatment in Patients With KRAS Wild-type, Unresectable LIver Metastases of colorEctal Cancer

The aim of this study is to explore whether cetuximab in combination with mFOLFOX6 as treatment could improve the resection rate in patients with KRAS wild-type, unresectable liver metastases of mCRC.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer; Liver Metastases
• Intervention / Treatment: Drug: Cetuximab; mFOLFOX6

Detailed Description

During the last decade, chemotherapy in metastatic colorectal cancer (mCRC) has made considerable progress.However, approximately 25% of patients with colorectal cancer present with overt metastatic disease. In selected patients, synchronous or metachronous liver metastases (LM) can be resected in curative intention. Over the last 5 years there has been the recognition that preoperative, neoadjuvant, combination chemotherapy regimens, namely, 5-fluorouracil/folinic acid (5-FU/FA) in combination with either irinotecan or oxaliplatin can facilitate to downsize the initially unresectable LM and make the resection possible. The addition of targeted therapies might render them even more effective.

Due to these results, the investigators hypothesize that cetuximab in combination with mFOLFOX6 as treatment in patients with KRAS wild-type, unresectable liver metastases of mCRC may further improve clinical outcomes.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Wenhua Li, MD; Phone Number: 8621-64175590; Email: whliiris@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female 18-75 years of age
• Performance status (ECOG) 0~1

• Unresectable, histologically confirmed, synchronous or metachronous liver metastasis of colorectal cancer. Unresectable liver metastases is defined as:

  • patients with five and more liver metastases and/or
  • Liver metastases that are technically unresectable immediately, and expected remaining functional liver tissue ≥ 30% after resection. (Patients should be evaluated by a multidisciplinary team of three local surgeons and one local radiologist, including surgical consultation for potentially resectable patients on the basis of remaining liver volume, infiltration of all liver veins, infiltration of both liver arteries, both portal branches or both bile ducts.)
• Tumor tissue (primary or metastasis) genotypologically classified as KRAS wild-type in codon 12 and codon 13 of the KRAS gene exon 2
• No prior chemotherapy (except adjuvant chemotherapy with an interval of ≥ 6 months)
• Presence of at least one index lesion of hepatic metastasis measurable by CT scan or MRI, not in an irradiated area
• Neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, and hemoglobin ≥ 8 g/dL
• Bilirubin level ≤ 1.0 x ULN
• AST and ALT < 1.5 x ULN
• Serum creatinine ≤ 1.0 x ULN
• Life expectancy of ≥ 3 months
• Male or female of child-bearing period should have effective contraception
• Signed written informed consent

Exclusion Criteria:

• Any investigational agent(s) within 4 weeks prior to entry
• Previous exposure to EGFR-targeting therapy
• Any evidence of extrahepatic metastases and/or primary tumor recurrence
• Total volumes of liver lesions > 70%
• Clinically relevant peripheral neuropathy
• Acute or sub-acute intestinal obstruction or history of inflammatory bowel disease
• Breast-feeding or pregnant women, no effective contraception if risk of conception exists (for male and female patients up to 4 months after end of chemotherapy)
• Previous malignancy (except colorectal cancer, history of basal cell carcinoma of skin or pre-invasive carcinoma of the cervix with adequate treatment)
• Known drug abuse/ alcohol abuse
• Known dihydropyrimidine dehydrogenase (DPD) deficiency
• Severe organ failures or diseases, including: clinically relevant coronary disease, cardiovascular disorder or myocardial infarction within 12 months before study entry, severe psychiatric illness, severe infection and DIC

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Resection rate (R0)	from the first cycle of treatment (day one) to two month after the last cycle

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	from the first cycle of treatment (day one) to six month after the last cycle
Response rate,Progression-free Survival,Overall Survival,R1 resection rate	from the first cycle of treatment (day one) to six month after the last cycle

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Sanjun Cai, PhD, Fudan University

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Anticipated): June 1, 2012
• Study Completion (Anticipated): December 1, 2013

Study Registration Dates

• First Submitted: March 23, 2011
• First Submitted That Met QC Criteria: March 23, 2011
• First Posted (Estimate): March 24, 2011

Study Record Updates

• Last Update Posted (Estimate): August 12, 2011
• Last Update Submitted That Met QC Criteria: August 11, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: cetuximab; colorectal carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: EMR 62202-203