FLOX + Cetuximab (Erbitux®) for Patients With Metastatic Colorectal Cancer and Wild Type K-RAS Tumor

Metastatic Colorectal Cancer Clinical Trial

Official title:

FLOX + Cetuximab (Erbitux®): First Line Treatment for Patients With Metastatic Colorectal Cancer and Wild Type K-RAS Tumor, A Phase II Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00660582
• Other study ID #: Nordic 7.5
• Status: Completed
• Phase: Phase 2
• First received: April 11, 2008
• Last updated: January 20, 2015
• Start date: April 2008
• Est. completion date: February 2013

Study information

• Verified date: January 2015
• Source: Odense University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial Summary

The Nordic FLOX-regime consists of a combination of bolus 5-FU, leukovorin and oxaliplatin (Eloxatin®). Cetuximab (Erbitux®) is an antibody against the epidermal growth factor receptor (EGFR). The combination of FLOX and weekly Erbitux has been investigated in the Nordic VII study where 571 patients were randomized to FLOX (regime A) or FLOX + Erbitux (regime B or C). Effect-data has not yet been published but the combination is well tolerated, and other studies have shown that Erbitux administered with chemotherapy seem to be more efficient than chemotherapy alone.

The main purpose with this study is to investigate the effect of FLOX and Erbitux given every second week as first line treatment for patients with metastatic colorectal cancer and K-RAS wildtype tumor.

The latest accessible data regarding treatment towards EGFR and K-RAS mutations shows that patients with K-RAS wildtype responds better to treatment than patients with K-RAS mutations.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: February 2013
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

Histology and staging disease:

• Histological proven adenocarcinoma of the colon or rectum

• At least one measurable metastatic lesion according to RECIST criteria

• If only one metastatic lesion, histology is mandatory

Mutation level:

• Tumor tissue (primary or metastasis) typological classified as K-RAS wildtype in codon 12 and 13 in exon 1 at real-time PCR

General conditions:

• Age >18 and < 75 years

• WHO performance status = 2; life expectancy of more than 3 months

• Adequate haematological function: (Hb = 6.2 µmol/d, ANC = 1.5 x 109/L, platelets = 100 x 109/L)

• Adequate renal and hepatic functions: total bilirubin = 1.5 upper normal limit, creatinine = 1.25 × upper normal limit, ALAT = 3 x upper normal limits, and = 5 x upper normal limits in case of liver metastases

• Written informed consent prior to randomisation must be obtained and documented according to the local regulatory requirements

Other:

• Fertile patients must use adequate contraceptives

Exclusion Criteria:

Prior therapy:

• Prior chemotherapy for advanced/metastatic disease

• Adjuvant chemotherapy must have ended > 6 months before inclusion

• Prior treatment with Eloxatin

• Prior treatment with Erbitux or other treatment to EGFR

Prior or current history:

• Current indication for resection with a curative intent

• Evidence of CNS metastasis

• Current infection, unresolved bowel obstruction or subobstruction, uncontrolled Crohn's disease or ulcerative colitis

• Current history of chronic diarrhea

• Peripheral neuropathy

• Other serious illness or medical conditions (including contraindication to 5 FU e.g.:

angor, myocardial infarction within 6 months, contraindications to monoclonal antibodies)

• Past or concurrent history of malignant neoplasm other than colorectal adenocarcinoma within the past five years, except curatively treated non melanoma skin cancer or in situ carcinoma of the cervix

Concomitant treatments:

• Concomitant (or within 4 weeks before randomisation) administration of any other experimental drug under investigation

• Concurrent treatment with any other anti-cancer therapy

Other:

• Pregnant or breast feeding women

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Cetuximab (Erbitux)
500 mg/m² every second week, intravenous infusion, 8 cycles
• Oxaliplatin (Eloxatin) + Fluorouracil + folinic acid
Given in combination day 1 and 2, every second week, 8 cycles

Locations

Country	Name	City	State
Denmark	Department of Oncology, Aalborg University Hospital	Aalborg
Denmark	Department of Oncology, Herlev University Hospital	Herlev
Denmark	Department of Oncology, Odense University Hospital	Odense
Norway	Department of Oncology, Haukeland University Hospital	Bergen
Norway	Kreftsenteret, Ullevaal University Hospital	Oslo
Sweden	Section of Oncology, Uppsala University Hospital	Uppsala

Sponsors (2)

Lead Sponsor	Collaborator
Per Pfeiffer	Odense University Hospital

Countries where clinical trial is conducted

Denmark,  Norway,  Sweden,