Leucovorin and Fluorouracil With or Without Oxaliplatin Compared to Capecitabine With or Without Oxaliplatin in Treating Patients With Metastatic Colorectal Cancer

NCT00070213 | Completed Phase 3 DMC

• 4 other identifiers: CDR0000330142NCRI-FOCUS2MRC-CR09EU-20303
• Study Type: interventional
• Target: 460
• Locations: 1 country
• Sites: 4

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as leucovorin, fluorouracil, capecitabine, and oxaliplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known whether leucovorin and fluorouracil with or without oxaliplatin is more effective than capecitabine with or without oxaliplatin in treating patients who have metastatic colorectal cancer. PURPOSE: This randomized phase III trial is studying four different chemotherapy regimens to compare how well they work in treating patients with metastatic colorectal cancer.

Conditions

Colorectal Cancer

Keywords

adenocarcinoma of the colon; adenocarcinoma of the rectum; stage IV rectal cancer; stage IV colon cancer; recurrent rectal cancer; recurrent colon cancer

Outcome Measures

Primary Outcomes (2)

• Compare progression-free survival (PFS) in pts. treated w/ leucovorin calcium + fluorouracil (MdG) vs leucovorin calcium + fluorouracil + oxaliplatin (OxMdG) and in pts. treated w/ capecitabine (Cap) vs capecitabine + oxaliplatin (OxCap) at 1 yr

  Compare progression-free survival (PFS) in pts. treated w/ leucovorin calcium + fluorouracil (MdG) vs leucovorin calcium + fluorouracil + oxaliplatin (OxMdG) and in pts. treated w/ capecitabine (Cap) vs capecitabine + oxaliplatin (OxCap) at 1 yr

  PFS

• Compare health assessment in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap at baseline and 14 weeks

  Compare health assessment in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap at baseline and 14 weeks

  Baseline and 14 weeks

Secondary Outcomes (10)

• Compare health assessment, including quality of life, in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap at baseline and 14 and 24 weeks

  Baseline, 14 and 24 weeks

• Compare toxicity/adverse events in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap

  post 24 weeks

• Compare overall failure-free survival in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap

  post 24 weeks

• Compare overall survival in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap

  post 24 weeks

• Compare health economics in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap

  Baseline, 14 and 24 weeks

Study Arms (4)

MdG (modified de Gramont)

ACTIVE COMPARATOR

2 weekly 5FU/FA schedule

Drug: FOLFOX regimen; Drug: fluorouracil; Drug: leucovorin calcium; Procedure: quality-of-life assessment

OxMdG (80%) for 12 weeks

EXPERIMENTAL

MdG + oxaliplatin

Drug: FOLFOX regimen; Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin; Procedure: quality-of-life assessment

Capcitabine

EXPERIMENTAL

Drug: capecitabine; Procedure: quality-of-life assessment

OxCap

EXPERIMENTAL

Drug: capecitabine; Drug: oxaliplatin; Procedure: quality-of-life assessment

Interventions

FOLFOX regimen DRUG

MdG (modified de Gramont); OxMdG (80%) for 12 weeks

capecitabine DRUG

Capcitabine; OxCap

fluorouracil DRUG

MdG (modified de Gramont); OxMdG (80%) for 12 weeks

leucovorin calcium DRUG

MdG (modified de Gramont); OxMdG (80%) for 12 weeks

oxaliplatin DRUG

OxCap; OxMdG (80%) for 12 weeks

quality-of-life assessment PROCEDURE

Capcitabine; MdG (modified de Gramont); OxCap; OxMdG (80%) for 12 weeks

Eligibility Criteria

• Age: 0 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Diagnosis of colorectal adenocarcinoma, defined by 1 of the following: * Prior or current histologically confirmed primary adenocarcinoma of the colon or rectum with clinical/radiological evidence of advanced/metastatic disease * Histologically or cytologically confirmed metastatic adenocarcinoma with clinical/radiological evidence of colorectal primary tumor * Unidimensionally measurable disease * Unfit and unsuitable for full-dose combination chemotherapy, which would include 1 of the following circumstances: * Unsuitable or unwilling to be entered into any full-dose chemotherapy protocol * Ineligible or unsuitable for first-line standard combination as per National Institute of Clinical Excellence guidance PATIENT CHARACTERISTICS: Age * Not specified Performance status * WHO 0-2 Life expectancy * Not specified Hematopoietic * WBC greater than 3,000/mm\^3 * Platelet count greater than 100,000/mm\^3 Hepatic * Bilirubin no greater than 3 times upper limit of normal (ULN) * AST or ALT no greater than 2.5 times ULN Renal * Creatinine clearance greater than 50 mL/min OR * Glomerular filtration rate greater than 30 mL/min Cardiovascular * No uncontrolled angina * No recent myocardial infarction Other * Not pregnant * Negative pregnancy test * Fertile patients must use effective contraception * No partial or complete bowel obstruction * No concurrent severe uncontrolled medical illness that would preclude study treatment * No psychiatric or neurological condition that would preclude giving informed consent or complying with oral study medication * No other prior or concurrent malignant disease that would preclude study treatment or assessment of response * No prior neuropathy greater than grade 1 PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * More than 4 months since prior adjuvant chemotherapy with fluorouracil with or without leucovorin calcium * More than 1 month since prior rectal chemoradiotherapy with fluorouracil with or without leucovorin calcium * No prior systemic palliative chemotherapy for metastatic disease Endocrine therapy * Not specified Radiotherapy * See Chemotherapy Surgery * Not specified Other * No concurrent brivudine or sorivudine

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Medical Research Council: lead
• University of Leeds: collaborator

Study Sites (4)

Cookridge Hospital

Leeds, England, LS16 6QB, United Kingdom

Location

Clinical Trials and Research Unit of the University of Leeds

Leeds, England, LS2 9JT, United Kingdom

Location

Medical Research Council Clinical Trials Unit

London, England, NW1 2DA, United Kingdom

Location

Velindre Cancer Center at Velindre Hospital

Cardiff, Wales, CF14 2TL, United Kingdom

Location

Related Publications (2)

• Seymour MT, Thompson LC, Wasan HS, Middleton G, Brewster AE, Shepherd SF, O'Mahony MS, Maughan TS, Parmar M, Langley RE; FOCUS2 Investigators; National Cancer Research Institute Colorectal Cancer Clinical Studies Group. Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial. Lancet. 2011 May 21;377(9779):1749-59. doi: 10.1016/S0140-6736(11)60399-1. Epub 2011 May 11.

  PMID: 21570111 RESULT

• Seymour MT, Maughan TS, Wasan HS, et al.: Capecitabine (Cap) and oxaliplatin (Ox) in elderly and/or frail patients with metastatic colorectal cancer: the FOCUS2 trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-9030, 500s, 2007.

  RESULT

Related Links

• Clinical trial summary from the National Cancer Institute's PDQ® database

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Folfox protocol; Capecitabine; Fluorouracil; Leucovorin; Oxaliplatin

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)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Matthew T. Seymour, MA, MD, FRCP

  Cookridge Hospital

  PRINCIPAL INVESTIGATOR

• Gareth Griffiths

  Medical Research Council

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Project manager for FOCUS2 for Sponsor

Study Record Dates

• First Submitted: October 3, 2003
• First Posted: October 7, 2003
• Study Start: September 1, 2003
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: September 27, 2021

Record last verified: 2021-09

Locations

GB (4)