Colorectal Cancer, Liver Metastases
Conditions
Keywords
cetuximab, colorectal carcinoma
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.
Interventions
DRUGCetuximab; 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)
Sponsors
Fudan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Resection rate (R0) | from the first cycle of treatment (day one) to two month after the last cycle |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
Countries
China
Contacts
Primary ContactSanjun Cai, phD
Outcome results
None listed