FLOX in Combination With Cetuximab in First-line Treatment of Colorectal Cancer

• ClinicalTrials.gov Identifier: NCT00145314
• Recruitment Status: Completed
• First Posted: September 5, 2005
• Last Update Posted: January 14, 2011
• Sponsor: The Nordic Colorectal Cancer Biomodulation Group
• Information provided by: The Nordic Colorectal Cancer Biomodulation Group

Tracking Information

• First Submitted Date: September 2, 2005
• First Posted Date: September 5, 2005
• Last Update Posted Date: January 14, 2011
• Study Start Date: May 2005
• Actual Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 31, 2008): 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 [ Time Frame: Every 4th cycle ]
• Original Primary Outcome Measures (submitted: September 2, 2005): 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
• Current Secondary Outcome Measures (submitted: January 31, 2008): To measure response rates, response duration, secondary surgical curative resection frequency, safety profile, overall survival and quality of life in the treatment groups. [ Time Frame: Every 2nd week (safety profile) ]
• Original Secondary Outcome Measures (submitted: September 2, 2005): To measure response rates, response duration, secondary surgical curative resection frequency, safety profile, overall survival and quality of life in the treatment groups.
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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.
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Colorectal Cancer

Intervention

• Drug: FLOX (5-fluorouracil/folinic acid/oxaliplatin)
  FLOX every 2nd week
• Drug: FLOX (5-fluorouracil/folinic acid/oxaliplatin) and Cetuximab
  FLOX every 2nd week Cetuximab weekly
• Drug: FLOX (5-fluorouracil and folinic acid and oxaliplatin) intermittently and maintenance cetuximab

  FLOX every 2nd week for 8 cycles. Stop of FLOX until progression then FLOX is reintroduced.

  Cetuximab weekly.

Study Arms

• Active Comparator: A
  FLOX: 5-fluorouracil/folinic acid/oxaliplatin; Nordic Regimen; given continuosly
  Intervention: Drug: FLOX (5-fluorouracil/folinic acid/oxaliplatin)
• Experimental: B
  FLOX: 5-fluorouracil/folinic acid/oxaliplatin and cetuximab
  Intervention: Drug: FLOX (5-fluorouracil/folinic acid/oxaliplatin) and Cetuximab
• Experimental: C
  FLOX given intermittently and maintenance cetuximab
  Intervention: Drug: FLOX (5-fluorouracil and folinic acid and oxaliplatin) intermittently and maintenance cetuximab

Publications *

• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 31, 2008): 571
• Original Enrollment (submitted: September 2, 2005): 550
• Actual Study Completion Date: August 2010
• Actual Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 74 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Norway

Administrative Information

• NCT Number: NCT00145314
• Other Study ID Numbers: Nordic VII; EudraCT no.: 2005-000117-34
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Kjell M. Tveit, MD, PhD, The Nordic Colorectal Cancer Biomodulation Group
• Original Responsible Party: Not Provided
• Current Study Sponsor: The Nordic Colorectal Cancer Biomodulation Group
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Kjell M. Tveit, MD, PhD; Professor at Ullevål University Hospital, Norway

• PRS Account: The Nordic Colorectal Cancer Biomodulation Group
• Verification Date: January 2011