Capecitabine and Oxaliplatin or Standard Follow-Up Care in Treating Patients Who Have Undergone Surgery for Locally Advanced Rectal Cancer

Colorectal Cancer Clinical Trial

Official title:

Chemotherapy or No Chemotherapy in Clear Margins After Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer. A Randomised Phase III Trial of Control Vs Capecitabine Plus Oxaliplatin [CHRONICLE]

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00427713
• Other study ID #: CDR0000526299
• Secondary ID: CRUK-CHRONICLECR
• Status: Completed
• Phase: Phase 3
• First received: January 25, 2007
• Last updated: August 23, 2013
• Start date: November 2004

Study information

• Verified date: June 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether giving capecitabine together with oxaliplatin is more effective than standard follow-up care in treating rectal cancer that was removed by surgery.

PURPOSE: This randomized phase III trial is studying capecitabine and oxaliplatin to see how well they work compared with standard follow-up care in treating patients who have undergone surgery for locally advanced rectal cancer.

Description:

OBJECTIVES:

• Compare the efficacy of adjuvant chemotherapy comprising capecitabine and oxaliplatin vs standard follow-up care, in terms of disease-free and overall survival, in patients with clear margins after complete resection of locally advanced rectal cancer.

OUTLINE: This is an open-label, randomized, controlled, prospective, multicenter study. Patients are stratified according to surgeon and nodal status (node positive vs node negative vs unknown). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo standard follow up.

• Arm II: Patients receive oral capecitabine twice daily on days 1-14 and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 5 years, and then annually thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 800 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 800
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the rectum

• Within 15 cm of the anal verge

• Locally advanced disease

• Underwent complete resection of primary tumor within the past 12 weeks

• ypT0-4, N0-2 with definitive histology at surgery

• Circumferential resection margin > 1 mm

• No gross evidence of residual disease

• Received neoadjuvant fluoropyrimidine-based chemoradiotherapy with = 45 Gy planned total radiation dose, given in 1 of the following fashions:

• Prolonged fluorouracil IV during radiotherapy

• Low-dose leucovorin calcium and fluorouracil (days 1-5 and 29-33) concurrently with radiotherapy

• Oral capecitabine concurrently with radiotherapy

• No evidence of metastatic disease

PATIENT CHARACTERISTICS:

• WHO performance status 0-1

• Absolute neutrophil count = 1,500/mm³

• Platelet count = 100,000/mm³

• Creatinine clearance = 50 mL/min

• Bilirubin = 1.25 times upper limit of normal (ULN)

• AST and ALT = 1.25 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for = 3 months after completion of study treatment

• No known dihydropyrimidine dehydrogenase deficiency

• No hypersensitivity to platinum compounds

• No preexisting peripheral neuropathy = grade 1

• No lack of physical integrity of the upper gastrointestinal tract

• No malabsorption syndrome

• No other serious uncontrolled medical condition or concurrent medical illness that would compromise life expectancy and/or preclude study compliance, including any of the following:

• Serious uncontrolled infections

• Significant cardiac disease (e.g., uncontrolled angina, congestive heart failure, cardiomyopathy, or arrhythmias) or myocardial infarction within the past 12 months

• Interstitial pneumonia or symptomatic lung fibrosis

• No other malignancies except adequately treated in situ carcinoma of the cervix or basal cell or squamous cell carcinoma of the skin, unless disease-free for = 10 years

• No history of uncontrolled seizures, CNS disorders, or psychiatric disability that would preclude study compliance

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior chemotherapy exceeding 6 weeks in duration

• Prior chemotherapy given as part of neoadjuvant treatment (i.e., chemoradiotherapy) may last a maximum of 11-12 weeks

• No prior oxaliplatin

• Prior mitomycin C, irinotecan hydrochloride, or cetuximab allowed

• No concurrent warfarin, antiviral agents, or phenytoin

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer

Intervention

Drug:
• capecitabine

• oxaliplatin

Procedure:
• adjuvant therapy

• standard follow-up care

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Wansbeck General Hospital	Ashington	England
United Kingdom	North Devon District Hospital	Barnstaple	England
United Kingdom	Furness General Hospital	Barrow in Furness	England
United Kingdom	Birmingham Heartlands Hospital	Birmingham	England
United Kingdom	Good Hope Hospital	Birmingham	England
United Kingdom	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust	Birmingham	England
United Kingdom	Blackpool Victoria Hospital	Blackpool	England
United Kingdom	Pilgrim Hospital	Boston	England
United Kingdom	Bristol Haematology and Oncology Centre	Bristol	England
United Kingdom	Queen's Hospital	Burton-upon-Trent	England
United Kingdom	Velindre Cancer Center at Velindre Hospital	Cardiff	Wales
United Kingdom	Cumberland Infirmary	Carlisle	England
United Kingdom	Broomfield Hospital	Chelmsford, Essex	England
United Kingdom	Gloucestershire Oncology Centre at Cheltenham General Hospital	Cheltenham	England
United Kingdom	Castle Hill Hospital	Cottingham	England
United Kingdom	Walsgrave Hospital	Coventry	England
United Kingdom	Derbyshire Royal Infirmary	Derby	England
United Kingdom	Doncaster Royal Infirmary	Doncaster	England
United Kingdom	University Hospital of North Durham	Durham	England
United Kingdom	Edinburgh Cancer Centre at Western General Hospital	Edinburgh	Scotland
United Kingdom	Princess Alexandra Hospital	Essex	England
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	Royal Bolton Hospital	Farnworth	England
United Kingdom	Queen Elizabeth Hospital	Gateshead	England
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	Gloucestershire Royal Hospital	Gloucester	England
United Kingdom	St. Luke's Cancer Centre at Royal Surrey County Hospital	Guildford	England
United Kingdom	Hereford Hospitals	Hereford
United Kingdom	Wycombe General Hospital	High Wycombe	England
United Kingdom	Princess Royal Hospital at Hull and East Yorkshire NHS Trust	Hull	England
United Kingdom	King George Hospital	Ilford, Essex	England
United Kingdom	Ipswich Hospital	Ipswich	England
United Kingdom	West Middlesex University Hospital	Isleworth	England
United Kingdom	Kidderminster Hospital	Kidderminster Worcestershire	England
United Kingdom	Royal Albert Edward Infirmary	Lancanshire	England
United Kingdom	Royal Lancaster Infirmary	Lancaster	England
United Kingdom	Cookridge Hospital	Leeds	England
United Kingdom	Royal Glamorgan Hospital	Lhantrisant	Wales
United Kingdom	Lincoln County Hospital	Lincoln	England
United Kingdom	Aintree University Hospital	Liverpool	England
United Kingdom	Charing Cross Hospital	London	England
United Kingdom	Helen Rollason Cancer Care Centre at North Middlesex Hospital	London	England
United Kingdom	Saint Bartholomew's Hospital	London	England
United Kingdom	St. George's Hospital	London	England
United Kingdom	UCL Cancer Institute	London	England
United Kingdom	University College of London Hospitals	London	England
United Kingdom	Whittington Hospital	London	England
United Kingdom	Macclesfield District General Hospital	Macclesfield	England
United Kingdom	Christie Hospital	Manchester	England
United Kingdom	Clatterbridge Centre for Oncology	Merseyside	England
United Kingdom	James Cook University Hospital	Middlesbrough	England
United Kingdom	St. Mary's Hospital	Newport	England
United Kingdom	Northampton General Hospital	Northampton	England
United Kingdom	Mount Vernon Cancer Centre at Mount Vernon Hospital	Northwood	England
United Kingdom	Churchill Hospital	Oxford	England
United Kingdom	Rosemere Cancer Centre at Royal Preston Hospital	Preston	England
United Kingdom	Oldchurch Hospital	Romford	England
United Kingdom	Hope Hospital	Salford	England
United Kingdom	Scarborough General Hospital	Scarborough
United Kingdom	Scunthorpe General Hospital	Scunthorpe	England
United Kingdom	Cancer Research Centre at Weston Park Hospital	Sheffield	England
United Kingdom	Royal Shrewsbury Hospital	Shrewsbury	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Southport and Formby District General Hospital	Southport	England
United Kingdom	Sunderland Royal Hospital	Sunderland	England
United Kingdom	Kingston Hospital	Surrey	England
United Kingdom	Walsall Manor Hospital	Walsall	England
United Kingdom	Sandwell General Hospital	West Bromwich	England
United Kingdom	Southend University Hospital NHS Foundation Trust	Westcliff-On-Sea	England
United Kingdom	Worcester Royal Hospital	Worcester	England
United Kingdom	Yeovil District Hospital	Yeovil	England

Sponsors (1)

Lead Sponsor	Collaborator
Cancer Research UK

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival at 3 years			No
Secondary	Overall survival at 5 years			No
Secondary	Toxicity			Yes