Combination Chemotherapy After Surgery in Treating Patients With High-Risk Stage II or Stage III Colorectal Cancer - Full Text View

Sponsor:	Greater Glasgow and Clyde NHS Board
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00749450

Purpose

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, fluorouracil, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known which combination chemotherapy regimen is more effective in treating patients who have undergone surgery for high-risk colorectal cancer.

PURPOSE: This randomized phase III trial is studying chemotherapy given after surgery in treating patients with high-risk stage II or stage III colorectal cancer.

Condition	Intervention	Phase
Colorectal Cancer	Drug: capecitabine Drug: fluorouracil Drug: oxaliplatin	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Masking: Open Label Primary Purpose: Treatment
Official Title:	Short Course Oncology Therapy - A Study of Adjuvant Chemotherapy in Colorectal Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Fluorouracil Oxaliplatin Capecitabine

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

3-year disease-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival [ Designated as safety issue: No ]
Cost-effectiveness [ Designated as safety issue: No ]
Toxicity according to NCI CTCAE Version 3.0 [ Designated as safety issue: Yes ]
Quality of life as assessed by EORTC QLQ-C30, EORTC QLQ-CR29, EQ-5D, and GOG Ntx4 [ Designated as safety issue: No ]

Estimated Enrollment:	9500
Study Start Date:	March 2008
Estimated Primary Completion Date:	March 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm I Patients receive OxMdG or XELOX combination chemotherapy for a total of 12 courses for treatment lasting a total of 24 weeks.	Drug: capecitabine Given orally Drug: fluorouracil Given IV Drug: oxaliplatin Given IV
Experimental: Arm II Patients receive OxMdG or XELOX combination chemotherapy for a total of 6 courses for treatment lasting a total of 12 weeks.	Drug: capecitabine Given orally Drug: fluorouracil Given IV Drug: oxaliplatin Given IV

Detailed Description:

OBJECTIVES:

To assess the efficacy and compare the associated toxicity of adjuvant chemotherapy lasting 12 weeks vs 24 weeks in patients with fully resected high-risk stage II or III colorectal cancer.
To conduct an economic analysis of the cost effectiveness of these regimens.
To compare the randomization methodologies used in this study.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center's recruitment potential. Patients are randomized (within 10 weeks after surgery and before or after receiving 12 weeks of chemotherapy) to 1 of 2 treatment arms. The treatment regimen that a patient receives (Oxaliplatin Modified DeGramont [OxMdG] or XELOX) is determined by the participating center.

Arm I: Patients receive 12 courses of OxMdG (described below) or XELOX (described below)combination chemotherapy (6 additional courses if patient already received 6 courses) for treatment lasting a total of 24 weeks.
Arm II: Patients receive 6 courses of OxMdG or XELOX combination chemotherapy (no additional courses if patient already received 6 courses) for treatment lasting a total of 12 weeks.

The two adjuvant combination chemotherapy regimens are administered as follows:

OxMdG: Patients receive oxaliplatin IV over 2 hours and fluorouracil IV continuously over 46 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.
XELOX: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients complete quality-of-life assessments periodically using the EORTC QLQ-C30, EORTC QLQ-CR29, EQ-5D, and GOG Ntx4 questionnaires.

After completion of study treatment, patients are followed periodically for up to 7 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of colorectal cancer meeting 1 of the following criteria:
- High-risk stage IIB disease, defined as T4 disease, perforation, obstruction, < 10 nodes examined, poorly differentiated histology, extramural venous invasion, or extramural lymphatic invasion
- Fully resected stage III disease
Patients with rectal cancer must meet the following criteria:
- Underwent prior total mesorectal excision surgery with negative resection (R0) margins
- No prior pre-operative or scheduled post-operative combined chemotherapy and radiotherapy
No evidence of residual or metastatic disease
Deemed suitable for adjuvant chemotherapy

PATIENT CHARACTERISTICS:

WHO performance status 0-1
Life expectancy > 5 years with reference to noncancer-related diseases
ANC ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 9 g/dL
AST and ALT ≤ 2.5 times upper limit of normal
Carcinoembryonic antigen (CEA) levels normal
Glomerular filtration rate ≥ 30 mL/min (no moderate or severe renal impairment)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must effective contraception
More than 12 months since prior and no active clinically significant cardiovascular disease, including any of the following:
- Cerebrovascular accident
- Myocardial infarction
- Unstable angina
- New York Heart Association class II-IV congestive heart failure
- Serious cardiac arrhythmia requiring medication
- Uncontrolled hypertension (i.e., blood pressure > 150/100 mm Hg)
Disease-free interval of ≥ 5 years for previous malignancy other than adequately treated in situ carcinoma of the uterine cervix or basal cell or squamous cell carcinoma of the skin
No known or suspected dihydropyrimidine dehydrogenase deficiency

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No more than 10 weeks since prior surgery and recovered
No prior chemotherapy (except in patients randomized after 12 weeks of adjuvant therapy)
No prior abdomino-pelvic radiotherapy, with the exception of short-course pre-operative radiotherapy for rectal cancer
No concurrent brivudine or sorivudine for patients taking capecitabine

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00749450

Locations

United Kingdom
Beatson West of Scotland Cancer Centre	Recruiting
Glasgow, Scotland, United Kingdom, G12 0YN
Contact: Jim Cassidy, MD, FRCP, MSC 44-141-211-2123

Sponsors and Collaborators

Greater Glasgow and Clyde NHS Board

Investigators

Principal Investigator:

Jim Cassidy, MD, FRCP, MSC

University of Glasgow

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier:	NCT00749450 History of Changes
Other Study ID Numbers:	CDR0000613042, CRUK-SCOT, ISRCTN59757862, EudraCT 2007-003957-10, EU-20874, SCOT-2007-01
Study First Received:	September 6, 2008
Last Updated:	July 7, 2009
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage II colon cancer
stage III colon cancer
stage II rectal cancer
stage III rectal cancer

Additional relevant MeSH terms:

Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil

Capecitabine
Oxaliplatin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 09, 2012