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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Merck KGaA
Information provided by (Responsible Party):
PD Dr. med. Volker Heinemann, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier:
NCT00433927
First received: February 9, 2007
Last updated: March 13, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Neoplasm Metastasis
Colorectal Cancer
Drug: 5-FU
Drug: folinic acid
Drug: irinotecan
Drug: cetuximab
Drug: bevacizumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter Randomized Trial Evaluating FOLFIRI Plus Cetuximab Versus FOLFIRI Plus Bevacizumab in First Line Treatment of Metastatic Colorectal Cancer.

Resource links provided by NLM:


Further study details as provided by Ludwig-Maximilians - University of Munich:

Primary Outcome Measures:
  • Objective response rate [ Time Frame: approximate 6 months after randomisation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Median progression free survival [ Time Frame: approximate 6 months after randomisation ] [ Designated as safety issue: No ]
  • Median overall survival [ Time Frame: approximate 3 years after randomisation ] [ Designated as safety issue: No ]
  • Secondary resection rate with curative intent [ Time Frame: up to 3 months after end of treatment ] [ Designated as safety issue: No ]
  • Safety and toxicity (according to NCI-CTCAE) [ Time Frame: approximate 6 months after randomisation ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 568
Study Start Date: January 2007
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00433927

Locations
Germany
University of Munich - Klinikum Grosshadern
Munich, Germany, 81377
Sponsors and Collaborators
PD Dr. med. Volker Heinemann
Merck KGaA
Investigators
Principal Investigator: Volker Heinemann, MD University of Munich - Klinikum Grosshadern
  More Information

No publications provided

Responsible Party: PD Dr. med. Volker Heinemann, Sponsor Delegated Person, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier: NCT00433927     History of Changes
Other Study ID Numbers: FIRE-3
Study First Received: February 9, 2007
Last Updated: March 13, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Ludwig-Maximilians - University of Munich:
metastatic

Additional relevant MeSH terms:
Neoplasms
Colorectal Neoplasms
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Fluorouracil
Irinotecan
Bevacizumab
Cetuximab
Leucovorin
Folic Acid
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 20, 2014