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

NCT00660582 | Completed Phase 2 DMC

• 1 other identifier: Nordic 7.5
• Study Type: interventional
• Target: 152
• Locations: 3 countries
• Sites: 6

Brief 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.

Conditions

Metastatic Colorectal Cancer

Keywords

Erbitux; Colorectal cancer; Oxaliplatin; Flox; Fluorouracil + folinic acid; K-RAS

Interventions

Cetuximab (Erbitux) DRUG

500 mg/m² every second week, intravenous infusion, 8 cycles

Oxaliplatin (Eloxatin) + Fluorouracil + folinic acid DRUG

Given in combination day 1 and 2, every second week, 8 cycles

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Prior therapy:
• Prior chemotherapy for advanced/metastatic disease
• 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

Sponsors & Collaborators

• Per Pfeiffer: lead
• Odense University Hospital: collaborator

Study Sites (6)

Department of Oncology, Aalborg University Hospital

Aalborg, 9800, Denmark

Location

Department of Oncology, Herlev University Hospital

Herlev, 2630, Denmark

Location

Department of Oncology, Odense University Hospital

Odense, 5000, Denmark

Location

Department of Oncology, Haukeland University Hospital

Bergen, Norway

Location

Kreftsenteret, Ullevaal University Hospital

Oslo, 0407, Norway

Location

Section of Oncology, Uppsala University Hospital

Uppsala, 751 85, Sweden

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Oxaliplatin; Fluorouracil; Leucovorin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Per Pfeiffer, MD

  Odense University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 11, 2008
• First Posted: April 17, 2008
• Study Start: April 1, 2008
• Primary Completion: May 1, 2011
• Study Completion: February 1, 2013
• Last Updated: January 21, 2015

Record last verified: 2015-01

Locations

DK (3); NO (2); SE (1)