search
Back to results

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

Primary Purpose

Colorectal Cancer, Liver Metastases

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Cetuximab; mFOLFOX6
Sponsored by
Fudan University
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring cetuximab, colorectal carcinoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Fudan University Shanghai Cancer CenterRecruiting

Outcomes

Primary Outcome Measures

Resection rate (R0)

Secondary Outcome Measures

Response rate,Progression-free Survival,Overall Survival,R1 resection rate
Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Full Information

First Posted
March 23, 2011
Last Updated
August 11, 2011
Sponsor
Fudan University
search

1. Study Identification

Unique Protocol Identification Number
NCT01322178
Brief Title
Study of Cetuximab in Combination With mFOLFOX-6 (Oxaliplatin, Leucovorin, 5-FU) to Treat Colorectal Liver Metastatic Cancer Patients
Acronym
CLIME
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2011
Overall Recruitment Status
Unknown status
Study Start Date
December 2010 (undefined)
Primary Completion Date
June 2012 (Anticipated)
Study Completion Date
December 2013 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
Fudan University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Liver Metastases
Keywords
cetuximab, colorectal carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Cetuximab; mFOLFOX6
Intervention Description
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)
Primary Outcome Measure Information:
Title
Resection rate (R0)
Time Frame
from the first cycle of treatment (day one) to two month after the last cycle
Secondary Outcome Measure Information:
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sanjun Cai, phD
Phone
8621-64175590
Email
caisanjun@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sanjun Cai, PhD
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wenhua Li, MD
Phone
8621-64175590
Email
whliiris@hotmail.com

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs