Cetuximab in Combination With Chemotherapy for the Treatment of Metastatic Colorectal Cancer

Sponsor

Xu jianmin (Other)

Overall Status

Unknown status

CT.gov ID

NCT01564810

Collaborator

(none)

150

Enrollment

Location

Arms

108

Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Colorectal Neoplasms Neoplasm Metastasis Liver Neoplasms	Drug: Cetuximab Drug: chemotherapy of mFOLFOX6 or FOLFIRI	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Study of Cetuximab in Combination With Chemotherapy for the First Treatment of Metastatic Colorectal Cancer

Study Start Date :

Sep 1, 2006

Actual Primary Completion Date :

Jun 1, 2012

Anticipated Study Completion Date :

Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A patients received cetuximab in combination with chemotherapy	Drug: Cetuximab On day 1 of a 14 day treatment cycle, patients received a 2-hour infusion of cetuximab (initial dose 400 mg/m2 in week 1, and 250 mg/m2 weekly during 1 hour thereafter) followed after 1 hour by chemotherapy of FOLFOX or FOLFIRI until progressive disease or unacceptable toxicity. Other Names: Erbitux Drug: chemotherapy of mFOLFOX6 or FOLFIRI FOLFOX-4 (oxaliplatin, 85mg/m2 on day 1 infused during 2 hours;LV200mg/m2ondays 1and 2 infused during 2 hours, together with or following oxaliplatin; followed by FU 400 mg/m2 intravenous bolus then 600 mg/m2 intravenous infusion over 22 hours on days 1 and 2) FOLFIRI(irinotecan 180mg/m2 on day 1 infused during 2 hours; fluorouracil in a bolus of 400 mg/m2 and then continuous infusion for 46 hours of 2400 mg/m2) Other Names: mFOLFOX6
Active Comparator: Arm B Patients received chemotherapy (mFOLFOX6 or FOLFIRI) alone. mFOLFOX6 (day 1, oxaliplatin 85 mg/m², folinic acid 400 mg/m², and fluorouracil 400 mg/m² intravenous bolus, then 2400 mg/m² over 46 h continuous infusion) FOLFIRI (day 1, irinotecan 180mg/m2, folinic acid 400 mg/m², and fluorouracil 400 mg/m² intravenous bolus, then continuous infusion for 46 hours of 2400 mg/m2).	Drug: chemotherapy of mFOLFOX6 or FOLFIRI FOLFOX-4 (oxaliplatin, 85mg/m2 on day 1 infused during 2 hours;LV200mg/m2ondays 1and 2 infused during 2 hours, together with or following oxaliplatin; followed by FU 400 mg/m2 intravenous bolus then 600 mg/m2 intravenous infusion over 22 hours on days 1 and 2) FOLFIRI(irinotecan 180mg/m2 on day 1 infused during 2 hours; fluorouracil in a bolus of 400 mg/m2 and then continuous infusion for 46 hours of 2400 mg/m2) Other Names: mFOLFOX6

Arm

Intervention/Treatment

Experimental: Arm A

patients received cetuximab in combination with chemotherapy

Drug: Cetuximab

On day 1 of a 14 day treatment cycle, patients received a 2-hour infusion of cetuximab (initial dose 400 mg/m2 in week 1, and 250 mg/m2 weekly during 1 hour thereafter) followed after 1 hour by chemotherapy of FOLFOX or FOLFIRI until progressive disease or unacceptable toxicity.

Other Names:

Erbitux

Drug: chemotherapy of mFOLFOX6 or FOLFIRI

FOLFOX-4 (oxaliplatin, 85mg/m2 on day 1 infused during 2 hours;LV200mg/m2ondays 1and 2 infused during 2 hours, together with or following oxaliplatin; followed by FU 400 mg/m2 intravenous bolus then 600 mg/m2 intravenous infusion over 22 hours on days 1 and 2) FOLFIRI(irinotecan 180mg/m2 on day 1 infused during 2 hours; fluorouracil in a bolus of 400 mg/m2 and then continuous infusion for 46 hours of 2400 mg/m2)

Other Names:

mFOLFOX6

Active Comparator: Arm B

Patients received chemotherapy (mFOLFOX6 or FOLFIRI) alone. mFOLFOX6 (day 1, oxaliplatin 85 mg/m², folinic acid 400 mg/m², and fluorouracil 400 mg/m² intravenous bolus, then 2400 mg/m² over 46 h continuous infusion) FOLFIRI (day 1, irinotecan 180mg/m2, folinic acid 400 mg/m², and fluorouracil 400 mg/m² intravenous bolus, then continuous infusion for 46 hours of 2400 mg/m2).

Drug: chemotherapy of mFOLFOX6 or FOLFIRI

Other Names:

mFOLFOX6

Outcome Measures

Primary Outcome Measures

the rate of patients converted to resection for liver metastases [3 years]
To explore whether cetuximab in combination with chemotherapy as treatment could improve the resection rate in patients with KRAS wild-type, unresectable colorectal liver-limited metastases compared with chemotherapy alone.

Secondary Outcome Measures

progression free survival [3 years]
PFS will be defined as the period from the first day of cetuximab treatment or chemotherapy to the date of disease progression (PD) or to death. Patients without PD who discontinued the study for any reason is censored at the last on-study tumor assessment date.
overall survival [3 years]
OS and MST will be calculated from randomization to death from any cause or the date of the last follow-up, at which point the data will be censored.
tumor response [3 years]
defined as partial and complete response according to RECIST 1.0 (Response Evaluation Criteria in Solid Tumors).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 and ≤ 75 years;
Primary tumour has undergone radical resection and histologically confirmed colorectal adenocarcinoma;
Together with clinical or radiological evidence of first occurrence of non-resectable synchronous liver-only metastases
With evidence of tumor EGFR expression and KRAS gene wild-type status;
With one measurable tumor.
Performance status (ECOG) 0~1
A life expectancy of ≥ 3 months
Adequate hematological function: Neutrophils≥1.5 x109/l and platelet count≥100 x109/l; Hb ≥9g/dl (within 1 week prior to randomization)
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);
Written informed consent for participation in the trial.

Exclusion Criteria:

Previous exposure to target therapy, chemotherapy, radiotherapy or intervention therapy for colorectal liver metastases.
Known or suspected extrahepatic metastases.
Patients with known hypersensitivity reactions to any of the components of the study treatments.
Having previously participated in a study which included a possibility of being allocated to cetuximab therapy (whether or not the patient actually received cetuximab)
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
Acute or sub-acute intestinal occlusion
Pregnancy (absence confirmed by serum/urine β-HCG) or breast-feeding
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
Known drug abuse/ alcohol abuse
Legal incapacity or limited legal capacity
Pre-existing peripheral neuropathy.