Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy in Treating Patients With Colorectal Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	Over 18	Other	EORTC-05011 NCT00039208

Objectives

1. 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.
2. Determine the antitumor activity of this regimen.

Entry 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

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

Patient Characteristics:

Age:

• Over 18

Performance status:

• WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Neutrophil count greater than 2,000/mm³
• Platelet count at least 90,000/mm³

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

Expected Enrollment

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

Outcomes

Peak delivery time for CPT11 tolerability over the first 3 courses of treatment in patients who started therapy

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
Peak delivery time for CPT11 activity over the first 3 courses
Peak delivery time for CPT11 tolerability and efficacy over the first 6 courses
Severe toxic events assessed by CTC v2.0 after each course of chemotherapy
Progression-free survival
Overall survival

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.

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.

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Carlo Garufi, MD, Study coordinator		Ph: 39-06-5266-5607

Registry Information
Official Title		Time Finding Study of Chronomodulated Irinotecan, 5 Fluorouracil, Leucovorin and Oxaliplatin as First or Second Chemotherapy Line Against Metastatic Colorectal Cancer
Trial Start Date		2002-02-07
Registered in ClinicalTrials.gov		NCT00039208
Date Submitted to PDQ		2002-04-09
Information Last Verified		2005-09-08

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