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]
18 Years
N/A
Both
Colorectal Cancer
Trial Information
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]
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Disease-free survival at 3 years
Safety Issue:
No
Principal Investigator
Robert Glynne-Jones, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Mount Vernon Cancer Centre at Mount Vernon Hospital
Authority:
Unspecified
Study ID:
CDR0000526299
NCT ID:
NCT00427713
Start Date:
November 2004
Completion Date:
Related Keywords:
- Colorectal Cancer
- adenocarcinoma of the rectum
- stage III rectal cancer
- stage II rectal cancer
- Rectal Neoplasms
- Colorectal Neoplasms
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