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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]

Phase 3
18 Years
Open (Enrolling)
Colorectal Cancer

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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]


- 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


- 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


- 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


- 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:


Study Design:

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

Outcome Measure:

Disease-free survival at 3 years

Safety Issue:


Principal Investigator

Robert Glynne-Jones, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Mount Vernon Cancer Centre at Mount Vernon Hospital



Study ID:




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