Clinical trial NCT00145314: FLOX in Combination With Cetuximab in First-line Treatment of Colorectal Cancer
Official title: 5-Fluorouracil/Folinate/Oxaliplatin (Eloxatin) (FLOX Regimen), Given Continuously or Intermittently, in Combination With Cetuximab (Erbitux), in First-line Treatment of Metastatic Colorectal Cancer. A Phase III Multicenter Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Keywords: Metastatic colorectal cancer
FLOX
Cetuximab
Lead sponsor: The Nordic Colorectal Cancer Biomodulation Group
Sponsor class: OTHER
First posted: 2005-09-05
Enrollment: 571
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main objective of this trial is to explore the effect of combining an established chemotherapy regimen (FLOX), based on 5-fluorouracil, folinic acid, and oxaliplatin (Eloxatin®), with the EGF receptor antibody cetuximab (Erbitux®) in first-line treatment of metastatic colorectal cancer. The trial will investigate two regimens of FLOX plus cetuximab, in which FLOX is given continuously or intermittently, compared to standard FLOX without cetuximab.


Eligibility criteria: Inclusion Criteria:

Histology and staging disease:

* Histological proven adenocarcinoma of the colon or rectum;
* At least one measurable metastatic disease
* If only one metastatic lesion and no S-CEA elevation, histology is mandatory;
* Availability of tumour sample for EGFR assessment.

General conditions:

* Age \>18 and \< 75 years;
* WHO performance status: life expectancy of more than 3 months;
* Adequate haematological function
* Adequate renal and hepatic functions
* Written informed consent

Exclusion Criteria:

Prior therapy:

* No prior chemotherapy for advanced/metastatic disease;
* No adjuvant chemotherapy the last 6 months before inclusion;
* No previous oxaliplatin;

Prior or current history:

* No current indication for resection with a curative intent;
* No evidence of CNS metastasis;
* No current infection, unresolved bowel obstruction or subobstruction, uncontrolled Crohn's disease or ulcerative colitis;
* No current history of chronic diarrhoea;
* No peripheral neuropathy;
* No other serious illness or medical conditions (including contraindication to 5 FU e.g.: angor, myocardial infarction within 6 months, contraindications to monoclonal antibodies);
* No 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:

* No concomitant (or within 4 weeks before randomisation) administration of any other experimental drug under investigation;
* No concurrent treatment with any other anti-cancer therapy;

Other:

* Not pregnant, no breast feeding
* Fertile patients must use adequate contraceptives
* Not include patients clearly intending to withdraw from the study if not randomised in the willing arm or patients who cannot be regularly followed up for psychological, social, familiar or geographic reasons.

Primary outcomes:
measure: To compare efficacy, as measured by time to disease progression, of treatment with cetuximab in combination with the FLOX regimen compared to FLOX alone, in first- line treatment of patients with metastatic cororectal cancer
timeFrame: Every 4th cycle
Secondary outcomes:
measure: To measure response rates, response duration, secondary surgical curative resection frequency, safety profile, overall survival and quality of life in the treatment groups.
timeFrame: Every 2nd week (safety profile)
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: The Nordic Colorectal Cancer Biomodulation Group
Study officials:
affiliation: Professor at Ullevål University Hospital, Norway
name: Kjell M. Tveit, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hamfjord J, Guren TK, Dajani O, Johansen JS, Glimelius B, Sorbye H, Pfeiffer P, Lingjaerde OC, Tveit KM, Kure EH, Pallisgaard N, Spindler KG. Total circulating cell-free DNA as a prognostic biomarker in metastatic colorectal cancer before first-line oxaliplatin-based chemotherapy. Ann Oncol. 2019 Jul 1;30(7):1088-1095. doi: 10.1093/annonc/mdz139.
citation: Kjersem JB, Thomsen M, Guren T, Hamfjord J, Carlsson G, Gustavsson B, Ikdahl T, Indrebo G, Pfeiffer P, Lingjaerde O, Tveit KM, Wettergren Y, Kure EH. AGXT and ERCC2 polymorphisms are associated with clinical outcome in metastatic colorectal cancer patients treated with 5-FU/oxaliplatin. Pharmacogenomics J. 2016 Jun;16(3):272-9. doi: 10.1038/tpj.2015.54. Epub 2015 Aug 11.
citation: Kjersem JB, Skovlund E, Ikdahl T, Guren T, Kersten C, Dalsgaard AM, Yilmaz MK, Fokstuen T, Tveit KM, Kure EH. FCGR2A and FCGR3A polymorphisms and clinical outcome in metastatic colorectal cancer patients treated with first-line 5-fluorouracil/folinic acid and oxaliplatin +/- cetuximab. BMC Cancer. 2014 May 19;14:340. doi: 10.1186/1471-2407-14-340.
citation: Kjersem JB, Ikdahl T, Guren T, Skovlund E, Sorbye H, Hamfjord J, Pfeiffer P, Glimelius B, Kersten C, Solvang H, Tveit KM, Kure EH. Let-7 miRNA-binding site polymorphism in the KRAS 3'UTR; colorectal cancer screening population prevalence and influence on clinical outcome in patients with metastatic colorectal cancer treated with 5-fluorouracil and oxaliplatin +/- cetuximab. BMC Cancer. 2012 Nov 20;12:534. doi: 10.1186/1471-2407-12-534.