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

July 26, 2018 updated by: Laura Alexander, Cancer Research UK, Glasgow

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

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.

Study Overview

Status

Completed

Conditions

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 Type

Interventional

Enrollment (Actual)

6088

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Scotland
      • Glasgow, Scotland, United Kingdom, G12 0YN
        • Beatson West of Scotland Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.
Given IV
Given IV
Given orally
Experimental: Arm II
Patients receive OxMdG or XELOX combination chemotherapy for a total of 6 courses for treatment lasting a total of 12 weeks.
Given IV
Given IV
Given orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
3-year disease-free survival
Time Frame: 3 years
3 years

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Tim Iveson, FRCP, MD, MRCP, MBBS, BSC, University Hospital Southampton NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2008

Primary Completion (Actual)

November 1, 2017

Study Registration Dates

First Submitted

September 6, 2008

First Submitted That Met QC Criteria

September 6, 2008

First Posted (Estimate)

September 9, 2008

Study Record Updates

Last Update Posted (Actual)

July 27, 2018

Last Update Submitted That Met QC Criteria

July 26, 2018

Last Verified

July 1, 2018

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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