Combination Chemotherapy in Treating Patients With Colorectal Cancer
Time Finding Study of Chronomodulated Irinotecan, 5 Fluorouracil, Leucovorin and Oxaliplatin as First or Second Chemotherapy Line Against Metastatic Colorectal Cancer
  • Phase

    Phase 2
  • Study Type

  • Status

    Completed No Results Posted
  • Study Participants

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.

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.
Study Started
Feb 28
Primary Completion
Aug 31
Last Update
Jul 13

Drug fluorouracil

Drug irinotecan hydrochloride

Drug leucovorin calcium

Drug oxaliplatin



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
No Results Posted