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

Fudan University

Status and phase

Unknown

Phase 2

Conditions

Liver Metastases

Colorectal Cancer

Treatments

Drug: Cetuximab; mFOLFOX6

Study type

Interventional

Funder types

Other

Identifiers

NCT01322178

EMR 62202-203

Details and patient eligibility

About

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.

Full 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.

Enrollment

90 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No 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