A study with two treatment arms to assess the efficacy of FOLFIRI (chemotherapy regimen with folinic acid, fluorouracil and irinotecan) in combinations with one specific antibody (cetuximab vs. bevacizumab) in the first-line treatment of metastatic colorectal cancer.

Phase 1

• Conditions: Metastatic colorectal cancer; MedDRA version: 19.0Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2006-004030-32-AT
• Lead Sponsor: Klinikum der Ludwig-Maximilians Universität München, Klinikum Großhadern

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-09-17
• Last Update Posted: 29 January 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 568

Inclusion Criteria

-Histologically confirmed adenocarcinoma of colon and rectum
-confirmation of a K-RAS wild type status (in the primary tumor or in metastasis)
-stage IV
-general condition: 0-2 (ECOG/ WHO)
-suitable for application of chemotherapy
-written informed consent (first and second-line therapy)
-Age 18- 75
-clinical or ambulant treatment
-Life expectancy > 3 months
-minimum one measurable indicator leasion according to RECIST. Evaluation of tumor manifestation 2 weeks or less before study entry.
-Male or female patients with reproductive potential must use an approved contraceptive method
-Leucocytes = 3,0 x 10\9/L with Neutrophils = 1,5 x 10\9/L, Thrombocytes = 100 10\9/L, Hemoglobin = 5,6 mmol/L equivalent to 9 g/dL
-Serum bilirubin = 1,5x upper NL
-ALAT and ASAT = 2,5 x upper NL, in case of liver metastases ALAT and ASAT = 5 x upper NL.
-Serum creatinine = 1,5 x upper NL
-An operation has to take place 4 weeks before study entry; a fine needle biopsy must have been performed more than 1 week ago. Wounds must have completely healed. The necessity of a big operation in the course of the study is not to be expected. An exception is a resection of liver metastases. If there should be the option of a secondary curative operation Bevacizumab has to be discontinued 6 to 8 weeks before operation.
-relevant toxicitys of therapies prior must have abated

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70

Exclusion Criteria

- confirmation of a K-RAS mutation
- previous exposure to EGFR-targeting therapy
- previous treatment with Bevacizumab
- prior chemotherapy of colorectal cancer, except adjuvant chemotherapy which was terminated at least 6 month before study entry
- experimental medical treatment within 30 days before study entry
- known hypersensitivity to elements of the study drug
- pregnant (exclusion diagnosis by beta-hCG-test) or breast-feeding women
- clinically relevant coronary disease or myocardial infarction within 12 months before study entry or enhanced risk of uncontrolled arrhythmia
- acute or subacute intestinal obstruction or chronical-inflammatory enteritis during anamnesis or chronical diarrhea
- symptomatic peritoneal carcinosis
- serious, non-healing wounds, ulcera or bone fracture
- uncontrolled hypertonia
- pronounced proteinuria
- arterial thromboembolism or haemorrhage within 6 months before study entry (except tumor bleeding before tumorresection)
- hemorrhagic diathesis or thrombotic tendency
- therapeutic anticoagulation (marcumar-therapy, PTT-effective heparinization)
- known DPD-insufficience (special screening not necessary)
- known glucuronisation defect (Gilbert´s disease) (special screening not necessary)
- secondary malignancies during anamnesis within the last 5 years except curatively treated basalioma or in situ carcinoma of the cervix
- known alcohol- or drug abuse
- clinical or psychological disorders that would prohibit to give a valid informed consent or to perform the study
- a significant concomitant disorder which excludes the patient´s participation in from the study in the opinion of the responsible physician
- absent or constricted legal capacity

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Comparative validation of antitumor efficacy measured by objective remissionrate defined by RECIST-criteria (OR= CR+ PR), assessed within intent-to-treat-collective.;Secondary Objective: Determination of progression free survival<br>Determination of overall survival<br>Rate of liver resection with potentially curative approach<br>Evaluation of safety and compatibility (NCI-CTCAE-criteria)<br>Determination of time to failure of strategy<br>Determination of remission depth (maximum relative remission of tumor burden compared to baseline);Primary end point(s): Progression of metastatic colorectal cancer or patient's death;Timepoint(s) of evaluation of this end point: Start of the end point evaluation is additive treatment with an antibody until tumor progression or death

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: Start of the end point evaluation is first the begin of tumor disease and second the additive antibody administration until tumor progression or patient death;Secondary end point(s): •progression free survival<br>•overall survival<br>•time to failure of strategy = TFS<br>•remission depth (maximum relative remission of tumor burden compared to baseline)<br>•rate of liver metastases resection with potentially curative approach<br>•Evaluation of safety and compatibility (NCI-CTCAE-V3.0 criteria)