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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00427713
First received: January 25, 2007
Last updated: August 23, 2013
Last verified: June 2007
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Drug: capecitabine
Drug: oxaliplatin
Procedure: adjuvant therapy
Procedure: standard follow-up care
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
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]

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Disease-free survival at 3 years [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival at 5 years [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment: 800
Study Start Date: November 2004
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Detailed 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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00427713

  Hide Study Locations
Locations
United Kingdom
Wansbeck General Hospital
Ashington, England, United Kingdom, NE63 9JJ
North Devon District Hospital
Barnstaple, England, United Kingdom, EX31 4JB
Furness General Hospital
Barrow in Furness, England, United Kingdom, LA14 4LF
Good Hope Hospital
Birmingham, England, United Kingdom, B75 7RR
Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
Birmingham, England, United Kingdom, B15 2TH
Birmingham Heartlands Hospital
Birmingham, England, United Kingdom, B9 5SS
Blackpool Victoria Hospital
Blackpool, England, United Kingdom, FY3 8NR
Pilgrim Hospital
Boston, England, United Kingdom, PE21 9QT
Bristol Haematology and Oncology Centre
Bristol, England, United Kingdom, BS2 8ED
Queen's Hospital
Burton-upon-Trent, England, United Kingdom, DE13 0RB
Cumberland Infirmary
Carlisle, England, United Kingdom, CA2 7HY
Broomfield Hospital
Chelmsford, Essex, England, United Kingdom, CM1 7ET
Gloucestershire Oncology Centre at Cheltenham General Hospital
Cheltenham, England, United Kingdom, GL53 7AN
Castle Hill Hospital
Cottingham, England, United Kingdom, HU16 5JQ
Walsgrave Hospital
Coventry, England, United Kingdom, CV2 2DX
Derbyshire Royal Infirmary
Derby, England, United Kingdom, DE1 2QY
Doncaster Royal Infirmary
Doncaster, England, United Kingdom, DN2 5LT
University Hospital of North Durham
Durham, England, United Kingdom, DH1 5TW
Princess Alexandra Hospital
Essex, England, United Kingdom, CM20 1QX
Royal Devon and Exeter Hospital
Exeter, England, United Kingdom, EX2 5DW
Royal Bolton Hospital
Farnworth, England, United Kingdom, BL4 0JR
Queen Elizabeth Hospital
Gateshead, England, United Kingdom, NE9 6SX
Gloucestershire Royal Hospital
Gloucester, England, United Kingdom, GL1 3NN
St. Luke's Cancer Centre at Royal Surrey County Hospital
Guildford, England, United Kingdom, GU2 7XX
Wycombe General Hospital
High Wycombe, England, United Kingdom
Princess Royal Hospital at Hull and East Yorkshire NHS Trust
Hull, England, United Kingdom, HU8 9HE
King George Hospital
Ilford, Essex, England, United Kingdom, IG3 8YB
Ipswich Hospital
Ipswich, England, United Kingdom, IP4 5PD
West Middlesex University Hospital
Isleworth, England, United Kingdom, TW7 6AF
Kidderminster Hospital
Kidderminster Worcestershire, England, United Kingdom, DY11 6RJ
Royal Albert Edward Infirmary
Lancanshire, England, United Kingdom, WN1 2NN
Royal Lancaster Infirmary
Lancaster, England, United Kingdom, LA1 4RP
Cookridge Hospital
Leeds, England, United Kingdom, LS16 6QB
Lincoln County Hospital
Lincoln, England, United Kingdom, LN2 5QY
Aintree University Hospital
Liverpool, England, United Kingdom, L9 7AL
St. George's Hospital
London, England, United Kingdom, SW17 0QT
University College of London Hospitals
London, England, United Kingdom, NW1 2PG
Charing Cross Hospital
London, England, United Kingdom, W6 8RF
Whittington Hospital
London, England, United Kingdom, N19 5NF
Helen Rollason Cancer Care Centre at North Middlesex Hospital
London, England, United Kingdom, N18 1QX
Saint Bartholomew's Hospital
London, England, United Kingdom, EC1A 7BE
UCL Cancer Institute
London, England, United Kingdom, NW1 2QG
Macclesfield District General Hospital
Macclesfield, England, United Kingdom, SK10 3BL
Christie Hospital
Manchester, England, United Kingdom, M20 4BX
Clatterbridge Centre for Oncology
Merseyside, England, United Kingdom, CH63 4JY
James Cook University Hospital
Middlesbrough, England, United Kingdom, TS4 3BW
St. Mary's Hospital
Newport, England, United Kingdom, PO30 5TG
Northampton General Hospital
Northampton, England, United Kingdom, NN1 5BD
Mount Vernon Cancer Centre at Mount Vernon Hospital
Northwood, England, United Kingdom, HA6 2RN
Churchill Hospital
Oxford, England, United Kingdom, OX3 7LJ
Rosemere Cancer Centre at Royal Preston Hospital
Preston, England, United Kingdom, PR2 9HT
Oldchurch Hospital
Romford, England, United Kingdom, RM7 OBE
Hope Hospital
Salford, England, United Kingdom, M6 8HD
Scunthorpe General Hospital
Scunthorpe, England, United Kingdom, DN15 7BH
Cancer Research Centre at Weston Park Hospital
Sheffield, England, United Kingdom, S10 2SJ
Royal Shrewsbury Hospital
Shrewsbury, England, United Kingdom, SY3 8XQ
Southampton General Hospital
Southampton, England, United Kingdom, SO16 6YD
Southport and Formby District General Hospital
Southport, England, United Kingdom, PR8 6PN
Sunderland Royal Hospital
Sunderland, England, United Kingdom, SR4 7TP
Kingston Hospital
Surrey, England, United Kingdom, KT2 7QB
Walsall Manor Hospital
Walsall, England, United Kingdom, WS2 9PS
Sandwell General Hospital
West Bromwich, England, United Kingdom, B71 4HJ
Southend University Hospital NHS Foundation Trust
Westcliff-On-Sea, England, United Kingdom, SS0 0RY
Worcester Royal Hospital
Worcester, England, United Kingdom, WR5 1DD
Yeovil District Hospital
Yeovil, England, United Kingdom, BA21 4AT
Aberdeen Royal Infirmary
Aberdeen, Scotland, United Kingdom, AB25 2ZN
Edinburgh Cancer Centre at Western General Hospital
Edinburgh, Scotland, United Kingdom, EH4 2XU
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, United Kingdom, G11 6NT
Velindre Cancer Center at Velindre Hospital
Cardiff, Wales, United Kingdom, CF14 2TL
Royal Glamorgan Hospital
Lhantrisant, Wales, United Kingdom, CF72 8XR
Hereford Hospitals
Hereford, United Kingdom, HR1 2ER
Scarborough General Hospital
Scarborough, United Kingdom, YO12 6QL
Sponsors and Collaborators
Cancer Research UK
Investigators
Study Chair: Robert Glynne-Jones, MD Mount Vernon Cancer Centre at Mount Vernon Hospital
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00427713     History of Changes
Other Study ID Numbers: CDR0000526299, CRUK-CHRONICLE, CRUK-BRD/05/132, EU-20679, ISRCTN59865116, CTA21106/0016/001, EUDRACT-2004-001484-21
Study First Received: January 25, 2007
Last Updated: August 23, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
adenocarcinoma of the rectum
stage III rectal cancer
stage II rectal cancer

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Oxaliplatin
Capecitabine
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 01, 2014