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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: Cetuximab (Erbitux); Drug: Oxaliplatin (Eloxatin) + Fluorouracil + folinic acid

• Study Type: Interventional
• Enrollment (Actual): 152
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9800
    • Department of Oncology, Aalborg University Hospital
  • Herlev, Denmark, 2630
    • Department of Oncology, Herlev University Hospital
  • Odense, Denmark, 5000
    • Department of Oncology, Odense University Hospital
• Norway
  • Bergen, Norway
    • Department of Oncology, Haukeland University Hospital
  • Oslo, Norway, 0407
    • Kreftsenteret, Ullevaal University Hospital
• Sweden
  • Uppsala, Sweden, 751 85
    • Section of Oncology, Uppsala University Hospital

Participation Criteria

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:

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: Per Pfeiffer
• Collaborators: Odense University Hospital
• Investigators: Principal Investigator: Per Pfeiffer, MD, Odense University Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: April 11, 2008
• First Submitted That Met QC Criteria: April 16, 2008
• First Posted (Estimate): April 17, 2008

Study Record Updates

• Last Update Posted (Estimate): January 21, 2015
• Last Update Submitted That Met QC Criteria: January 20, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Colorectal cancer; Oxaliplatin; Erbitux; Flox; Fluorouracil + folinic acid; K-RAS
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Immunological; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Hematinics; Fluorouracil; Oxaliplatin; Leucovorin; Levoleucovorin; Folic Acid; Cetuximab
• Other Study ID Numbers: Nordic 7.5