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

August 11, 2011 updated by: Fudan University

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

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)

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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) Time Frame: from the first cycle of treatment (day one) to two month after the last cycle	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 Time Frame: from the first cycle of treatment (day one) to six month after the last cycle	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 Time Frame: from the first cycle of treatment (day one) to six month after the last cycle	from the first cycle of treatment (day one) to six month after the last cycle

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fudan University

Investigators

Principal Investigator: Sanjun Cai, PhD, Fudan University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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