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

Primary Purpose

Colorectal Cancer

Status

Completed

Phase

Phase 3

Locations

United Kingdom

Study Type

Interventional

Intervention

capecitabine

fluorouracil

oxaliplatin

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring stage II colon cancer, stage III colon cancer, stage II rectal cancer, stage III rectal cancer

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Beatson West of Scotland Cancer Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm I

Arm II

Arm Description

Patients receive OxMdG or XELOX combination chemotherapy for a total of 12 courses for treatment lasting a total of 24 weeks.

Patients receive OxMdG or XELOX combination chemotherapy for a total of 6 courses for treatment lasting a total of 12 weeks.

Outcomes

Primary Outcome Measures

3-year disease-free survival

Secondary Outcome Measures

Overall survival

Cost-effectiveness

Toxicity according to NCI CTCAE Version 3.0

Quality of life as assessed by EORTC QLQ-C30, EORTC QLQ-CR29, EQ-5D, and GOG Ntx4

Full Information

NCT ID

NCT00749450

First Posted

September 6, 2008

Last Updated

July 26, 2018

Sponsor

Cancer Research UK, Glasgow

1. Study Identification

Unique Protocol Identification Number

NCT00749450

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2018

Overall Recruitment Status

Completed

Study Start Date

March 2008 (undefined)

Primary Completion Date

November 2017 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Cancer Research UK, Glasgow

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Cancer

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

6088 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm I

Arm Type

Experimental

Arm Description

Patients receive OxMdG or XELOX combination chemotherapy for a total of 12 courses for treatment lasting a total of 24 weeks.

Arm Title

Arm II

Arm Type

Experimental

Arm Description

Patients receive OxMdG or XELOX combination chemotherapy for a total of 6 courses for treatment lasting a total of 12 weeks.

Intervention Type

Drug

Intervention Name(s)

capecitabine

Intervention Description

Given orally

Intervention Type

Drug

Intervention Name(s)

fluorouracil

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

oxaliplatin

Intervention Description

Given IV

Primary Outcome Measure Information:

Title

3-year disease-free survival

Time Frame

3 years

Secondary Outcome Measure Information:

Title

Overall survival

Time Frame

assessed during 5 year recruitment period and maximum 7 year follow up period

Title

Cost-effectiveness

Time Frame

assessed during 5 year recruitment period

Title

Toxicity according to NCI CTCAE Version 3.0

Time Frame

assessed during 5 year recruitment period

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tim Iveson, FRCP, MD, MRCP, MBBS, BSC

Organizational Affiliation

University Hospital Southampton NHS Foundation Trust

Official's Role

Principal Investigator

Facility Information:

Facility Name

Beatson West of Scotland Cancer Centre

City

Glasgow

State/Province

Scotland

ZIP/Postal Code

G12 0YN

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

36306483

Citation

Gallois C, Shi Q, Meyers JP, Iveson T, Alberts SR, de Gramont A, Sobrero AF, Haller DG, Oki E, Shields AF, Goldberg RM, Kerr R, Lonardi S, Yothers G, Kelly C, Boukovinas I, Labianca R, Sinicrope FA, Souglakos I, Yoshino T, Meyerhardt JA, Andre T, Papamichael D, Taieb J. Prognostic Impact of Early Treatment and Oxaliplatin Discontinuation in Patients With Stage III Colon Cancer: An ACCENT/IDEA Pooled Analysis of 11 Adjuvant Trials. J Clin Oncol. 2023 Feb 1;41(4):803-815. doi: 10.1200/JCO.21.02726. Epub 2022 Oct 28.

Results Reference

derived

PubMed Identifier

33439695

Citation

Iveson TJ, Sobrero AF, Yoshino T, Souglakos I, Ou FS, Meyers JP, Shi Q, Grothey A, Saunders MP, Labianca R, Yamanaka T, Boukovinas I, Hollander NH, Galli F, Yamazaki K, Georgoulias V, Kerr R, Oki E, Lonardi S, Harkin A, Rosati G, Paul J. Duration of Adjuvant Doublet Chemotherapy (3 or 6 months) in Patients With High-Risk Stage II Colorectal Cancer. J Clin Oncol. 2021 Feb 20;39(6):631-641. doi: 10.1200/JCO.20.01330. Epub 2021 Jan 13. Erratum In: J Clin Oncol. 2021 May 20;39(15):1691.

Results Reference

derived

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

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