A Randomized Phase I/III Study Of Systematic Chemotherapy With Or Without Hepatic Chemoembolization For Liver-Dominant Metastatic Adenocarcinoma Of The Colon And Rectum
- Compare the survival of patients with liver-dominant metastatic colorectal
adenocarcinoma treated with irinotecan, fluorouracil, and leucovorin calcium with or
without hepatic chemoembolization.
- Compare response in the liver, time to hepatic tumor progression, and time to
extrahepatic tumor progression in patients treated with these regimens.
- Compare the possible treatment differences with respect to morbidity, toxic effects of
chemoembolization, toxic effects of chemotherapy, and death from cancer-related
complications in these patients.
OUTLINE: This is a phase I dose-escalation study followed by a phase III randomized,
multicenter study. (Phase I closed as of 10/14/02.)
- Phase I: Patients in phase I are sequentially enrolled to 1 of 3 treatment regimens.
(Phase I closed as of 10/14/02.)
- Regimen A: Patients receive irinotecan IV over 60-90 minutes, leucovorin calcium
IV, and fluorouracil IV over 10 minutes on days 1, 8, 15, and 22. Patients undergo
hepatic embolization with embolic suspension only on day 36.
- Regimen B: Patients receive chemotherapy as in regimen A. Patients undergo hepatic
chemoembolization with lower-dose cisplatin, doxorubicin, and mitomycin on day 36.
- Regimen C: Patients receive chemotherapy as in regimen A. Patients undergo hepatic
chemoembolization with higher-dose cisplatin, doxorubicin, and mitomycin on day
After 1 week of rest, patients in all regimens receive a second 4-week course of systemic
Cohorts of 3-10 patients are sequentially enrolled until the maximum tolerated dose (MTD) of
chemotherapy and chemoembolization is determined. The MTD is defined as the dose preceding
that at which at least 4 of 10 patients experience dose-limiting toxicity.
- Phase III: Patients are stratified according to liver volume involvement (less than 25%
vs 25-50% vs more than 50% to less than 75%) and participating center. Patients are
randomized to 1 of 2 treatment arms.
- Arm I: Patients receive irinotecan IV over 60-90 minutes, leucovorin calcium IV,
and fluorouracil IV over 10 minutes on days 1, 8, 15, and 22. Courses repeat every
6 weeks in the absence of disease progression.
- Arm II: Patients receive chemotherapy as in arm I. Patients undergo hepatic
chemoembolization with cisplatin, doxorubicin, and mitomycin on day 36.
Chemotherapy repeats every 6 weeks in the absence of disease progression.
Chemoembolization may repeat every 6 weeks for 2-4 courses as necessary.
Patients in phase III are followed every 3 months for 2 years, every 6 months for 3 years,
and then annually thereafter.
PROJECTED ACCRUAL: A total of 9-18 patients will be accrued for phase I of this study.
(Phase I closed to accrual as of 10/14/02.) Approximately 315 patients will be accrued for
phase III of this study within 2.5 years.
Allocation: Randomized, Primary Purpose: Treatment
Michael C. Soulen, MD
Abramson Cancer Center of the University of Pennsylvania
United States: Federal Government
|Arizona Cancer Center||Tucson, Arizona 85724|
|University of Texas - MD Anderson Cancer Center||Houston, Texas 77030-4009|
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|
|University of Pennsylvania Cancer Center||Philadelphia, Pennsylvania 19104|
|Robert H. Lurie Comprehensive Cancer Center, Northwestern University||Chicago, Illinois 60611|
|State University of New York - Upstate Medical University||Syracuse, New York 13210|
|Beth Israel Deaconess Medical Center||Boston, Massachusetts 02215|
|NYU School of Medicine's Kaplan Comprehensive Cancer Center||New York, New York 10016|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|