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Combination Chemotherapy in Treating Patients With Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00039208
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : July 13, 2012
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving drugs at the time of day that allows for the best drug response may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Randomized phase II trial to determine the best time to give irinotecan combined with fluorouracil, leucovorin, and oxaliplatin in treating patients who have colorectal cancer.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium Drug: oxaliplatin Phase 2

Detailed Description:


  • Determine the role of peak delivery time on the tolerability of irinotecan when administered with chronomodulated fluorouracil, leucovorin calcium, and oxaliplatin as first- or second-line therapy in patients with locoregional or metastatic colorectal cancer.
  • Determine the antitumor activity of this regimen.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, WHO performance status (0-1 vs 2), and line of treatment (first vs second). Patients are randomized to receive irinotecan at 1 of 6 different times of the day.

Patients receive irinotecan IV over 6 hours on day 1 and fluorouracil IV and leucovorin calcium IV over 11 hours followed by oxaliplatin IV over 11 hours on days 2-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 4 weeks until disease progression and then every 8 weeks thereafter.

PROJECTED ACCRUAL: A maximum of 186 patients (31 per irinotecan administration time) will be accrued for this study within 2 years.

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Study Type : Interventional  (Clinical Trial)
Allocation: Randomized
Primary Purpose: Treatment
Official Title: Time Finding Study of Chronomodulated Irinotecan, 5 Fluorouracil, Leucovorin and Oxaliplatin as First or Second Chemotherapy Line Against Metastatic Colorectal Cancer
Study Start Date : February 2002
Actual Primary Completion Date : August 2005

Primary Outcome Measures :
  1. Peak delivery time for CPT11 tolerability over the first 3 courses of treatment in patients who started therapy

Secondary Outcome Measures :
  1. Peak delivery time for CPT11 tolerability over the first 3 courses of treatment in patients who started therapy, excluding those who stopped prior to course 3 for reasons other than toxicity
  2. Peak delivery time for CPT11 activity over the first 3 courses
  3. Peak delivery time for CPT11 tolerability and efficacy over the first 6 courses
  4. Severe toxic events assessed by CTC v2.0 after each course of chemotherapy
  5. Progression-free survival
  6. Overall survival

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed colorectal cancer
  • Unresectable metastatic or locoregional disease
  • At least 1 measurable lesion outside a previously irradiated area or an area treated with physical devices (e.g., cryotherapy, laser, or thermoablation)
  • No prior enrollment in EORTC-05963
  • No symptomatic brain metastases



  • Over 18

Performance status:

  • WHO 0-2

Life expectancy:

  • Not specified


  • Neutrophil count greater than 2,000/mm^3
  • Platelet count at least 90,000/mm^3


  • Bilirubin no greater than 2 times upper limit of normal (ULN)


  • Creatinine no greater than 1.5 times ULN
  • No uncontrolled hypercalcemia


  • No overt cardiac disease


  • No severe respiratory illness


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Male patients must use effective barrier contraception during and for up to 6 months after study
  • No baseline diarrhea greater than grade I (must have less than 4 stools per 24 hours)
  • No prior grade III or IV toxicity related to irinotecan
  • No sensory or motor neuropathy with functional impairment
  • No prior hypersensitivity to any study drug
  • No other primary tumor except basal cell skin cancer or carcinoma in situ of the cervix
  • No uncontrolled infectious or chronic disease
  • No psychological, familial, sociological, or geographical condition that would preclude study


Biologic therapy:

  • No concurrent prophylactic growth factor therapy


  • At least 1 month since prior chemotherapy
  • No prior irinotecan, fluorouracil, leucovorin calcium, and oxaliplatin as combination therapy
  • Other prior therapy containing irinotecan and/or oxaliplatin allowed
  • No more than 1 prior chemotherapy regimen for metastatic or locoregional disease
  • Adjuvant chemotherapy considered first-line therapy if tumor relapsed within 6 months of completion of therapy

Endocrine therapy:

  • No concurrent corticosteroids except for emergencies


  • See Disease Characteristics
  • Palliative radiotherapy for bone lesion allowed except for disease progression


  • See Disease Characteristics

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00039208

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Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
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Study Chair: Carlo Garufi, MD Istituti Fisioterapici Ospitalieri - Roma
Publications of Results:
Garufi C, Focan C, Tumolo S, et al.: Time finding study of chronomodulated irinotecan (I), fluorouracil (F), leucovorin (L) and oxaliplatin (O) (chronoIFLO) against metastatic colorectal cancer: results from randomized EORTC 05011 trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-2566, 2007.

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Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC Identifier: NCT00039208    
Other Study ID Numbers: EORTC-05011
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: July 13, 2012
Last Verified: July 2012
Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
stage III colon cancer
stage IV colon cancer
stage III rectal cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Protective Agents