Clinical trial NCT00660582: FLOX + Cetuximab (Erbitux®) for Patients With Metastatic Colorectal Cancer and Wild Type K-RAS Tumor
Official title: FLOX + Cetuximab (Erbitux®): First Line Treatment for Patients With Metastatic Colorectal Cancer and Wild Type K-RAS Tumor, A Phase II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: Erbitux
Colorectal cancer
Oxaliplatin
Flox
Fluorouracil + folinic acid
K-RAS
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
Collaborators: name: Odense University Hospital
First posted: 2008-04-17
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Department of Oncology, Aalborg University Hospital
city: Herlev
country: Denmark
facility: Department of Oncology, Herlev University Hospital
city: Odense
country: Denmark
facility: Department of Oncology, Odense University Hospital
city: Bergen
country: Norway
facility: Department of Oncology, Haukeland University Hospital
city: Oslo
country: Norway
facility: Kreftsenteret, Ullevaal University Hospital
city: Uppsala
country: Sweden
facility: Section of Oncology, Uppsala University Hospital
Study officials:
affiliation: Odense University Hospital
name: Per Pfeiffer, MD
role: PRINCIPAL_INVESTIGATOR
References: