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

Colorectal Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01564810
• Other study ID #: 2012-03
• Status: Recruiting
• Phase: Phase 4
• First received: March 26, 2012
• Last updated: October 23, 2012
• Start date: September 2006
• Est. completion date: September 2015

Study information

• Verified date: October 2012
• Source: Fudan University
• Contact: jianmin xu jianmin xu, doctor
• Phone: 008613501984869
• Email: xujmin[@]yahoo.com.cn
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: September 2015
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 ß-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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Liver Neoplasms
• Neoplasm Metastasis
• Neoplasms

Intervention

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.
• 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)

Locations

Country	Name	City	State
China	Zhongshan Hospital, Fudan University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Xu jianmin

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the rate of patients converted to resection for liver metastases	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.	3 years	Yes
Secondary	progression free survival	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.	3 years	Yes
Secondary	overall survival	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.	3 years	Yes
Secondary	tumor response	defined as partial and complete response according to RECIST 1.0 (Response Evaluation Criteria in Solid Tumors).	3 years	Yes