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

  Show 72 Study Locations
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 by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Capecitabine
Oxaliplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 30, 2014