5-FU, Folinic Acid and Irinotecan (FOLFIRI) Plus Cetuximab Versus FOLFIRI Plus Bevacizumab in First Line Treatment Colorectal Cancer (CRC)

Colorectal Cancer Clinical Trial

Official title:

Multicenter Randomized Trial Evaluating FOLFIRI Plus Cetuximab Versus FOLFIRI Plus Bevacizumab in First Line Treatment of Metastatic Colorectal Cancer.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00433927
• Other study ID #: FIRE-3
• Status: Active, not recruiting
• Phase: Phase 3
• First received: February 9, 2007
• Last updated: March 13, 2014
• Start date: January 2007
• Est. completion date: December 2016

Study information

• Verified date: March 2014
• Source: Ludwig-Maximilians - University of Munich
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

The FIRE-3 trial is a multicenter randomized phase III trial investigating 5-FU, folinic acid and irinotecan (FOLFIRI) plus cetuximab versus FOLFIRI plus bevacizumab in first line treatment of metastatic colorectal cancer. Planned accrual is 284 evaluable patients per treatment arm. The primary study endpoint is objective response rate. Secondary endpoints are median progression free survival, median overall survival, safety, and secondary resection rate.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 568
• Est. completion date: December 2016
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• KRAS-Wildtype status

• Histologically confirmed adenocarcinoma of the colon or rectum.

• Stage IV disease.

• ECOG 0-2.

• Patients considered suitable for application of chemotherapy.

• Age 18 - 75 years.

• In- or outpatient treatment.

• Estimated life expectancy > 3 months.

• Measurable index lesion according to RECIST criteria. Evaluation of tumor manifestations = 2 weeks prior to treatment start.

• Effective contraception.

• Adequate hematologic function: leukocytes >= 3000/µl, neutrophils >= 1500/µl, platelets >= 100.000/µ, and hemoglobin >= 9g/dl.

• Bilirubin <= 1,5x upper limit of normal (ULN).

• ALAT and ASAT <= 2,5x ULN, in case of liver metastases <= 5x ULN.

• Serum creatinine <= 1,5x ULN.

• No operations within 4 weeks prior to treatment start. No cytologic biopsies within 1 week prior to treatment start. Operation sequels need to be completely healed. Major operations must not be expected at time of study begin, except for potential secondary resection of liver metastases. In case of secondary resection of liver metastases, bevacizumab must be discontinued 6-8 weeks prior to surgery.

• No relevant toxicities due to prior medical treatment at time of study entry.

Exclusion Criteria:

• KRAS-Mutation of the tumor

• Prior treatment directed against the epidermal growth factor receptor (EGFR).

• Prior treatment with bevacizumab.

• Prior chemotherapy for colorectal cancer, except for adjuvant chemotherapy dating back > 6 months prior to study entry.

• Experimental medical treatment within 30 days prior to study entry.

• Known hypersensitivity reaction to any study medication.

• Pregnant or breast feeding women (pregnancy needs to be excluded by testing of beta-HCG).

• Known or suspected cerebral metastases.

• Clinically significant coronary heart disease, myocardial infarction within the last 12 months or high risk of uncontrolled arrhythmia.

• Acute or subacute ileus, chronic inflammatory bowel disease or chronic diarrhea.

• Symptomatic peritoneal carcinosis.

• Severe chronic wounds, ulcera or bone fracture.

• Uncontrolled hypertension.

• Severe proteinuria (nephrotic syndrome).

• Arterial thromboembolic events or hemorrhage within 6 months prior to study entry (except tumor bleeding surgically treated by tumor resection).

• Bleeding diatheses or coagulopathy.

• Full dose anticoagulation.

• Known DPD-deficiency (special screening not required).

• Known glucuronidation-deficiency (special screening not required).

• Medical history of other malignant disease within 5 years prior to study entry, except for basalioma, and in-situ cervical carcinoma if treated with curative intent.

• Known alcohol or drug abuse.

• Medical or psychiatric condition which contradicts participation of study.

• Limited legal capacity.

Study Design

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Neoplasm Metastasis

Intervention

Drug:
• 5-FU
5-FU 400 mg/m² Bolus day 1 5-FU 2400 mg/m² iv over 46 h day 1-2
• folinic acid
Folinsäure (racemisch) 400 mg/m² iv, 120 min d 1
• irinotecan
Irinotecan 180 mg/m² iv, 30 - 90 min day 1
• cetuximab
Cetuximab initial 400mg/m² as 120 min infusion, than 250 mg/m² iv as 60 min infusion d 1 + 8
• bevacizumab
Bevacizumab 5 mg/kg iv over 30 to 90 minutes d 1

Locations

Country	Name	City	State
Germany	University of Munich - Klinikum Grosshadern	Munich

Sponsors (2)

Lead Sponsor	Collaborator
PD Dr. med. Volker Heinemann	Merck KGaA

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate		approximate 6 months after randomisation	No
Secondary	Median progression free survival		approximate 6 months after randomisation	No
Secondary	Median overall survival		approximate 3 years after randomisation	No
Secondary	Secondary resection rate with curative intent		up to 3 months after end of treatment	No
Secondary	Safety and toxicity (according to NCI-CTCAE)		approximate 6 months after randomisation	Yes