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

Sponsor

Cancer Research UK, Glasgow (Other)

Overall Status

Completed

CT.gov ID

NCT00749450

Collaborator

(none)

6,088

Enrollment

Location

Arms

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: capecitabine Drug: fluorouracil Drug: oxaliplatin	Phase 3

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 by Medical Research Council (MRC)

Study Design

Study Type:

Interventional

Actual Enrollment :

6088 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Short Course Oncology Therapy - A Study of Adjuvant Chemotherapy in Colorectal Cancer

Study Start Date :

Mar 1, 2008

Actual Primary Completion Date :

Nov 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

3-year disease-free survival [3 years]

Secondary Outcome Measures

Overall survival [assessed during 5 year recruitment period and maximum 7 year follow up period]
Cost-effectiveness [assessed during 5 year recruitment period]
Toxicity according to NCI CTCAE Version 3.0 [assessed during 5 year recruitment period]
Quality of life as assessed by EORTC QLQ-C30, EORTC QLQ-CR29, EQ-5D, and GOG Ntx4 [assessed during 5 year recruitment period]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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