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

This study is currently recruiting participants.
Verified August 2011 by Fudan University
Sponsor:
Information provided by:
Fudan University
ClinicalTrials.gov Identifier:
NCT01322178
First received: March 23, 2011
Last updated: August 11, 2011
Last verified: August 2011
History of Changes
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Liver Metastases
 Drug: Cetuximab; mFOLFOX6
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Fudan University:

Primary Outcome Measures:
  • Resection rate (R0) [ Time Frame: from the first cycle of treatment (day one) to two month after the last cycle ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 90
Study Start Date: December 2010
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Cetuximab; mFOLFOX6

    Cetuximab (Erbitux): 500 mg/m2 iv gtt, D1

    Oxaliplatin: 85 mg/m2 iv gtt over 2 hours, D1; leucovorin: 400 mg/m2 iv gtt , D1; 5-FU: 400 mg/m2 iv, 2400 mg/m2 civ46h

    repeated every two weeks for 4.5 months(9 cycles)

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01322178

Contacts
Contact: Sanjun Cai, phD 8621-64175590 caisanjun@gmail.com

Locations
China, Shanghai
Fudan University Shanghai Cancer Center Recruiting
Shanghai, Shanghai, China
Contact: Wenhua Li, MD     8621-64175590     whliiris@hotmail.com    
Sponsors and Collaborators
Fudan University
Investigators
Principal Investigator: Sanjun Cai, PhD Fudan University
  More Information

No publications provided

Responsible Party: Sanjun Cai, Fudan University Shanghai Cancer Center
ClinicalTrials.gov Identifier: NCT01322178     History of Changes
Other Study ID Numbers: EMR 62202-203
Study First Received: March 23, 2011
Last Updated: August 11, 2011
Health Authority: China: Ethics Committee

Keywords provided by Fudan University:
cetuximab
colorectal carcinoma

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Liver Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
 Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Liver Diseases
Oxaliplatin
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 13, 2013