Combination Chemotherapy in Treating Patients With Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00039208
First received: June 6, 2002
Last updated: July 12, 2012
Last verified: July 2012
  Purpose

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 Intervention Phase
Colorectal Cancer
Drug: fluorouracil
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Drug: oxaliplatin
Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Peak delivery time for CPT11 tolerability over the first 3 courses of treatment in patients who started therapy [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Designated as safety issue: Yes ]
  • Peak delivery time for CPT11 activity over the first 3 courses [ Designated as safety issue: No ]
  • Peak delivery time for CPT11 tolerability and efficacy over the first 6 courses [ Designated as safety issue: Yes ]
  • Severe toxic events assessed by CTC v2.0 after each course of chemotherapy [ Designated as safety issue: Yes ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]

Study Start Date: February 2002
Primary Completion Date: August 2005 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age:

  • Over 18

Performance status:

  • WHO 0-2

Life expectancy:

  • Not specified

Hematopoietic:

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

Hepatic:

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

Renal:

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

Cardiovascular:

  • No overt cardiac disease

Pulmonary:

  • No severe respiratory illness

Other:

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No concurrent prophylactic growth factor therapy

Chemotherapy:

  • 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

Radiotherapy:

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

Surgery:

  • See Disease Characteristics
  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: NCT00039208

Locations
Belgium
Centre Hospitalier Notre Dame - Reine Fabiola
Charleroi, Belgium, 6000
Clinique Saint-Joseph
Liege, Belgium, B 4000
CHU Liege - Domaine Universitaire du Sart Tilman
Liege, Belgium, B-4000
Clinique Sainte Elisabeth
Namur, Belgium, 5000
Centre Hospitalier Peltzer-La Tourelle
Verviers, Belgium, B-4800
France
Centre Jean Perrin
Clermont-Ferrand, France, 63011
Centre de Lutte Contre le Cancer Georges-Francois Leclerc
Dijon, France, 21079
Centre Hospital Regional Universitaire de Limoges
Limoges, France, 87042
Hopital Saint-Louis
Paris, France, 75475
Centre Rene Huguenin
Saint Cloud, France, 92211
Hopital Paul Brousse
Villejuif, France, 94804
Italy
Azienda Sanitaria di Bolzano
Bolzano, Italy, 39100
Universita G.D'Annunzio Di Chieti
Chieti, Italy, 66100
Ospedale San Carlo Borromeo
Milano (Milan), Italy, 20153
Azienda Ospedale S. Luigi at University of Torino
Orbassano, (Torino), Italy, 10043
Fondazione Salvatore Maugeri
Pavia, Italy, I-27100
Ospedale Oncologico Regionale
RIONERO in VULTURE, Italy, I-58028
Istituto Regina Elena
Rome, Italy, 00161
Istituto Clinico Beato Matteo
Vigevano, Italy, 27029
Portugal
Hospital Fernando Fonseca
Amadora, Portugal, P-2700
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Chair: Carlo Garufi, MD Istituti Fisioterapici Ospitalieri - Roma
  More Information

Additional Information:
Publications:
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.

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00039208     History of Changes
Other Study ID Numbers: EORTC-05011, EORTC-05011
Study First Received: June 6, 2002
Last Updated: July 12, 2012
Health Authority: United States: Federal Government

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:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Oxaliplatin
Irinotecan
Fluorouracil
Levoleucovorin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on October 16, 2014