Clinical trial NCT01564810: Cetuximab in Combination With Chemotherapy for the Treatment of Metastatic Colorectal Cancer
Official title: Study of Cetuximab in Combination With Chemotherapy for the First Treatment of Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Colorectal Neoplasms
Neoplasm Metastasis
Liver Neoplasms
Keywords: liver metastasis
colorectal cancer
cetuximab
chemotherapy
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2012-03-28
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this study, the investigators assessed the effect of Cetuximab in combination with chemotherapy in the treatment of unresectable metastatic colorectal cancer.

Detailed description: Patients will be eligible for inclusion if their primary tumors have been resected and if the patients have histologically confirmed wild-type-KRAS colorectal adenocarcinoma with synchronous liver-confined metastases deemed non-resectable. Eligible patients will be randomly assigned to chemotherapy plus cetuximab (arm A) or chemotherapy alone (arm B). Treatment will be planned to commence between 2 and 4 weeks after the primary surgery. Treatment will continue until tumor response indicates suitability for surgery for liver metastases or until disease progression or unacceptable toxic effects. The primary endpoint is the conversion rate to radical resection for liver metastases，which will be assessed by local multidisciplinary team (includes more than three liver surgeons and one radiologist) with the use of contrast-enhanced CT or MRI after 4 cycles and then every other 2 cycles up to 12 cycles. To provide an objective assessment of changes in resectability, radiological images will be presented by a radiologist to more than 3 liver surgeons, who are blinded to the clinical data. Patients will be considered resectable if 50% or more of surgeons vote for radical resection of LM. For patients whose liver-metastases are assessed resectable, resection should be scheduled to be performed within 2\~3 weeks of the last treatment cycle. Following resection, patients will be advised to continue the same therapeutic regimen until the treatments reach a sum of 12 cycles.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 and ≤ 75 years;
2. Primary tumour has undergone radical resection and histologically confirmed colorectal adenocarcinoma;
3. Together with clinical or radiological evidence of first occurrence of non-resectable synchronous liver-only metastases
4. With evidence of tumor EGFR expression and KRAS gene wild-type status;
5. With one measurable tumor.
6. Performance status (ECOG) 0\~1
7. A life expectancy of ≥ 3 months
8. Adequate hematological function: Neutrophils≥1.5 x109/l and platelet count≥100 x109/l; Hb ≥9g/dl (within 1 week prior to randomization)
9. Adequate hepatic and renal function: Serum bilirubin≤1.5 x upper limit of normal (ULN), alkaline phosphatase ≤5x ULN, and serum transaminase (either AST or ALT) ≤ 5 x ULN(within 1 week prior to randomization);
10. Written informed consent for participation in the trial.

Exclusion Criteria:

1. Previous exposure to target therapy, chemotherapy, radiotherapy or intervention therapy for colorectal liver metastases.
2. Known or suspected extrahepatic metastases.
3. Patients with known hypersensitivity reactions to any of the components of the study treatments.
4. Having previously participated in a study which included a possibility of being allocated to cetuximab therapy (whether or not the patient actually received cetuximab)
5. Clinically relevant coronary artery disease or a history of a myocardial infarction within the last 12 months or left ventricular ejection fraction (LVEF) below the institutional range of normal
6. Acute or sub-acute intestinal occlusion
7. Pregnancy (absence confirmed by serum/urine β-HCG) or breast-feeding
8. Other previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix
9. Known drug abuse/ alcohol abuse
10. Legal incapacity or limited legal capacity
11. Pre-existing peripheral neuropathy.

Primary outcomes:
measure: the rate of patients converted to resection for liver metastases
timeFrame: 3 years
Secondary outcomes:
measure: progression free survival
timeFrame: 3 years
measure: overall survival
timeFrame: 3 years
measure: tumor response
timeFrame: 3 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
state: Shanghai
Study officials:
References:
citation: Ye LC, Liu TS, Ren L, Wei Y, Zhu DX, Zai SY, Ye QH, Yu Y, Xu B, Qin XY, Xu J. Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases. J Clin Oncol. 2013 Jun 1;31(16):1931-8. doi: 10.1200/JCO.2012.44.8308. Epub 2013 Apr 8.