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

March 13, 2014 updated by: PD Dr. med. Volker Heinemann

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

568

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Munich, Germany, 81377
        • University of Munich - Klinikum Grosshadern

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Objective response rate
Time Frame: approximate 6 months after randomisation
approximate 6 months after randomisation

Secondary Outcome Measures

Outcome Measure
Time Frame
Median progression free survival
Time Frame: approximate 6 months after randomisation
approximate 6 months after randomisation
Median overall survival
Time Frame: approximate 3 years after randomisation
approximate 3 years after randomisation
Secondary resection rate with curative intent
Time Frame: up to 3 months after end of treatment
up to 3 months after end of treatment
Safety and toxicity (according to NCI-CTCAE)
Time Frame: approximate 6 months after randomisation
approximate 6 months after randomisation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

PD Dr. med. Volker Heinemann

Collaborators

Merck KGaA, Darmstadt, Germany

Investigators

  • Principal Investigator: Volker Heinemann, MD, University of Munich - Klinikum Grosshadern

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2007

Primary Completion (Anticipated)

April 1, 2014

Study Completion (Anticipated)

December 1, 2016

Study Registration Dates

First Submitted

February 9, 2007

First Submitted That Met QC Criteria

February 9, 2007

First Posted (Estimate)

February 12, 2007

Study Record Updates

Last Update Posted (Estimate)

March 14, 2014

Last Update Submitted That Met QC Criteria

March 13, 2014

Last Verified

March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FIRE-3

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Neoplasm Metastasis

Clinical Trials on 5-FU

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Greece

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe