Clinical trial NCT00427713: Capecitabine and Oxaliplatin or Standard Follow-Up Care in Treating Patients Who Have Undergone Surgery for Locally Advanced Rectal Cancer
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]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: adenocarcinoma of the rectum
stage III rectal cancer
stage II rectal cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-01-29
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Disease-free survival at 3 years
Secondary outcomes:
measure: Overall survival at 5 years
measure: Toxicity
Other outcomes:
Locations:
city: Ashington
country: United Kingdom
facility: Wansbeck General Hospital
state: England
city: Barnstaple
country: United Kingdom
facility: North Devon District Hospital
state: England
city: Barrow in Furness
country: United Kingdom
facility: Furness General Hospital
state: England
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
state: England
city: Birmingham
country: United Kingdom
facility: Good Hope Hospital
state: England
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
state: England
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospital
state: England
city: Boston
country: United Kingdom
facility: Pilgrim Hospital
state: England
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Burton-upon-Trent
country: United Kingdom
facility: Queen's Hospital
state: England
city: Carlisle
country: United Kingdom
facility: Cumberland Infirmary
state: England
city: Chelmsford, Essex
country: United Kingdom
facility: Broomfield Hospital
state: England
city: Cheltenham
country: United Kingdom
facility: Gloucestershire Oncology Centre at Cheltenham General Hospital
state: England
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital
state: England
city: Coventry
country: United Kingdom
facility: Walsgrave Hospital
state: England
city: Derby
country: United Kingdom
facility: Derbyshire Royal Infirmary
state: England
city: Doncaster
country: United Kingdom
facility: Doncaster Royal Infirmary
state: England
city: Durham
country: United Kingdom
facility: University Hospital of North Durham
state: England
city: Essex
country: United Kingdom
facility: Princess Alexandra Hospital
state: England
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: England
city: Farnworth
country: United Kingdom
facility: Royal Bolton Hospital
state: England
city: Gateshead
country: United Kingdom
facility: Queen Elizabeth Hospital
state: England
city: Gloucester
country: United Kingdom
facility: Gloucestershire Royal Hospital
state: England
city: Guildford
country: United Kingdom
facility: St. Luke's Cancer Centre at Royal Surrey County Hospital
state: England
city: High Wycombe
country: United Kingdom
facility: Wycombe General Hospital
state: England
city: Hull
country: United Kingdom
facility: Princess Royal Hospital at Hull and East Yorkshire NHS Trust
state: England
city: Ilford, Essex
country: United Kingdom
facility: King George Hospital
state: England
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
state: England
city: Isleworth
country: United Kingdom
facility: West Middlesex University Hospital
state: England
city: Kidderminster Worcestershire
country: United Kingdom
facility: Kidderminster Hospital
state: England
city: Lancanshire
country: United Kingdom
facility: Royal Albert Edward Infirmary
state: England
city: Lancaster
country: United Kingdom
facility: Royal Lancaster Infirmary
state: England
city: Leeds
country: United Kingdom
facility: Cookridge Hospital
state: England
city: Lincoln
country: United Kingdom
facility: Lincoln County Hospital
state: England
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital
state: England
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
state: England
city: London
country: United Kingdom
facility: Helen Rollason Cancer Care Centre at North Middlesex Hospital
state: England
city: London
country: United Kingdom
facility: Whittington Hospital
state: England
city: London
country: United Kingdom
facility: University College of London Hospitals
state: England
city: London
country: United Kingdom
facility: UCL Cancer Institute
state: England
city: London
country: United Kingdom
facility: St. George's Hospital
state: England
city: London
country: United Kingdom
facility: Charing Cross Hospital
state: England
city: Macclesfield
country: United Kingdom
facility: Macclesfield District General Hospital
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: England
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
state: England
city: Newport
country: United Kingdom
facility: St. Mary's Hospital
state: England
city: Northampton
country: United Kingdom
facility: Northampton General Hospital
state: England
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre at Mount Vernon Hospital
state: England
city: Oxford
country: United Kingdom
facility: Churchill Hospital
state: England
city: Preston
country: United Kingdom
facility: Rosemere Cancer Centre at Royal Preston Hospital
state: England
city: Romford
country: United Kingdom
facility: Oldchurch Hospital
state: England
city: Salford
country: United Kingdom
facility: Hope Hospital
state: England
city: Scunthorpe
country: United Kingdom
facility: Scunthorpe General Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Shrewsbury
country: United Kingdom
facility: Royal Shrewsbury Hospital
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Southport
country: United Kingdom
facility: Southport and Formby District General Hospital
state: England
city: Sunderland
country: United Kingdom
facility: Sunderland Royal Hospital
state: England
city: Surrey
country: United Kingdom
facility: Kingston Hospital
state: England
city: Walsall
country: United Kingdom
facility: Walsall Manor Hospital
state: England
city: West Bromwich
country: United Kingdom
facility: Sandwell General Hospital
state: England
city: Westcliff-On-Sea
country: United Kingdom
facility: Southend University Hospital NHS Foundation Trust
state: England
city: Worcester
country: United Kingdom
facility: Worcester Royal Hospital
state: England
city: Yeovil
country: United Kingdom
facility: Yeovil District Hospital
state: England
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre at Western General Hospital
state: Scotland
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Scotland
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
city: Lhantrisant
country: United Kingdom
facility: Royal Glamorgan Hospital
state: Wales
city: Hereford
country: United Kingdom
facility: Hereford Hospitals
city: Scarborough
country: United Kingdom
facility: Scarborough General Hospital
Study officials:
affiliation: Mount Vernon Cancer Centre at Mount Vernon Hospital
name: Robert Glynne-Jones, MD
role: STUDY_CHAIR
References:
citation: Glynne-Jones R, Counsell N, Quirke P, Mortensen N, Maraveyas A, Meadows HM, Ledermann J, Sebag-Montefiore D. Chronicle: results of a randomised phase III trial in locally advanced rectal cancer after neoadjuvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (XELOX) versus control. Ann Oncol. 2014 Jul;25(7):1356-1362. doi: 10.1093/annonc/mdu147. Epub 2014 Apr 8.