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

NCT ID: NCT00070213

Last Updated: 2021-09-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 460 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-09-30
• Study Completion Date: 2011-06-01

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.

Detailed Description

OBJECTIVES:

Primary

• Compare the progression-free survival of patients with metastatic colorectal adenocarcinoma treated with leucovorin calcium and fluorouracil with vs without oxaliplatin or capecitabine with vs without oxaliplatin.
• Compare the quality of life of patients treated with these fluorouracil-based vs capecitabine-based regimens.

Secondary

• Compare the failure-free and overall survival of patients treated with these regimens.
• Compare the toxic effects and adverse events associated with these regimens in these patients.
• Compare the limited health assessments of patients treated with these regimens.
• Compare the health economics associated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 4 treatment arms and receive 12 weeks of therapy.

• Arm I (MdG regimen): Patients receive leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients with disease progression during or within 8 weeks of the completion of this regimen may cross over and receive second-line therapy on arm II.

• Arm II (OxMdG regimen): Patients receive leucovorin calcium IV over 2 hours and oxaliplatin IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients with disease progression during or within 8 weeks of the completion of this regimen may receive second-line therapy or supportive care off-study.

• Arm III (Cap regimen): Patients receive oral capecitabine twice daily on days 1-15. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Patients with disease progression during or within 8 weeks of the completion of this regimen may cross over and receive second-line therapy on arm IV.

• Arm IV (OxCap regimen): Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-15. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Patients with disease progression during or within 8 weeks of the completion of this regimen may receive second-line therapy or supportive care off-study.

All patients are then re-evaluated at least every 6 weeks and begin another 12 weeks of therapy at any evidence (e.g., clinical, radiological, or tumor marker) of disease progression. Patients with chemo-sensitive disease may repeat alternating 12-week therapy sessions and evaluation periods indefinitely.

Quality of life is assessed at baseline, at 12-14 weeks, at 24 weeks, and then every 3 months thereafter.

Patients are followed every 3 months.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 460 patients (115 per treatment arm) will be accrued for this study within 2 years.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT

Study Groups

MdG (modified de Gramont)

2 weekly 5FU/FA schedule

Group Type: ACTIVE_COMPARATOR

FOLFOX regimen

Intervention Type: DRUG

fluorouracil

Intervention Type: DRUG

leucovorin calcium

Intervention Type: DRUG

quality-of-life assessment

Intervention Type: PROCEDURE

OxMdG (80%) for 12 weeks

MdG + oxaliplatin

Group Type: EXPERIMENTAL

FOLFOX regimen

Intervention Type: DRUG

fluorouracil

Intervention Type: DRUG

leucovorin calcium

Intervention Type: DRUG

oxaliplatin

Intervention Type: DRUG

quality-of-life assessment

Intervention Type: PROCEDURE

Capcitabine

Group Type: EXPERIMENTAL

capecitabine

Intervention Type: DRUG

quality-of-life assessment

Intervention Type: PROCEDURE

OxCap

Group Type: EXPERIMENTAL

capecitabine

Intervention Type: DRUG

oxaliplatin

Intervention Type: DRUG

quality-of-life assessment

Intervention Type: PROCEDURE

Interventions

FOLFOX regimen

Intervention Type: DRUG

capecitabine

Intervention Type: DRUG

fluorouracil

Intervention Type: DRUG

leucovorin calcium

Intervention Type: DRUG

oxaliplatin

Intervention Type: DRUG

quality-of-life assessment

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Leeds

OTHER

Sponsor Role: collaborator

Medical Research Council

OTHER_GOV

Sponsor Role: lead

Responsible Party

Cheryl Pugh

Clinical Project manager for FOCUS2 for Sponsor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Matthew T. Seymour, MA, MD, FRCP

Role: PRINCIPAL_INVESTIGATOR

Cookridge Hospital

Gareth Griffiths

Role: STUDY_CHAIR

Medical Research Council

Locations

Cookridge Hospital

Leeds, England, United Kingdom

Clinical Trials and Research Unit of the University of Leeds

Leeds, England, United Kingdom

Medical Research Council Clinical Trials Unit

London, England, United Kingdom

Velindre Cancer Center at Velindre Hospital

Cardiff, Wales, United Kingdom

Countries

United Kingdom

References

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.

Reference Type: RESULT

PMID: 21570111 (View on PubMed)

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.

Reference Type: RESULT

Related Links

https://events.cancer.gov/sites/default/files/assets/DCP-olderadultaccrual/Study%20Design%20and%20Assessment.pdf

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

Other Identifiers

NCRI-FOCUS2

Identifier Type: -

Identifier Source: secondary_id

MRC-CR09

Identifier Type: -

Identifier Source: secondary_id

EU-20303

Identifier Type: -

Identifier Source: secondary_id

CDR0000330142

Identifier Type: -

Identifier Source: org_study_id