Combination Chemotherapy With or Without Chemoembolization in Treating Patients With Colorectal Cancer Metastatic to the Liver

A Randomized Phase I/III Study Of Systematic Chemotherapy With Or Without Hepatic Chemoembolization For Liver-Dominant Metastatic Adenocarcinoma Of The Colon And Rectum


Hauptsponsor: American College of Radiology Imaging Network

Mitarbeiter: National Cancer Institute (NCI)

Quelle National Cancer Institute (NCI)
Kurze Zusammenfassung

RATIONALE: Drugs used in chemotherapy, such as irinotecan, fluorouracil, and leucovorin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping the cells from dividing. Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs near the tumor. It is not yet known if chemoembolization is more effective than standard chemotherapy in treating metastatic cancer.

PURPOSE: This phase I trial and randomized phase III trial is studying the effectiveness of chemoembolization in treating patients who have colorectal cancer metastatic to the liver.

detaillierte Beschreibung


- 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 36.

After 1 week of rest, patients in all regimens receive a second 4-week course of systemic chemotherapy.

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.

Gesamtstatus Completed
Anfangsdatum November 2001
Phase Phase 3
Studientyp Interventional

Interventionsart: Drug

Interventionsname: FOLFIRI regimen

Interventionsart: Drug

Interventionsname: cisplatin

Interventionsart: Drug

Interventionsname: doxorubicin hydrochloride

Interventionsart: Drug

Interventionsname: fluorouracil

Interventionsart: Drug

Interventionsname: irinotecan hydrochloride

Interventionsart: Drug

Interventionsname: leucovorin calcium

Interventionsart: Drug

Interventionsname: mitomycin C




- Histologically confirmed metastatic colorectal adenocarcinoma

- Measurable metastasis to liver at least 1.0 cm

- Less than 75% of total liver volume

- Known extrahepatic disease limited to lymph nodes and less than 2 cm

- No ascites

- Ineligible for surgery



- 18 and over

Performance status:

- Zubrod 0-2

Life expectancy:

- Not specified


- Absolute granulocyte count at least 2,000/mm^3

- Platelet count at least 90,000/mm^3

- No bleeding diathesis not correctable by standard therapy


- Ineligible if all of the following criteria are concurrently present:

- High risk of hepatic failure (more than 50% liver involvement by tumor)

- Bilirubin greater than 2.0 mg/dL

- SGOT greater than 100 U/L

- Lactate dehydrogenase greater than 425 U/L

- No hepatic encephalopathy

- No portal vein occlusion without hepatopedal collateral flow demonstrated by angiography

- No portal hypertension with hepatofugal flow


- Creatinine no greater than 2.0 mg/dL


- No myocardial infarction within the past 6 months

- No evidence of congestive heart failure

- No severe peripheral vascular disease that would preclude catheterization


- No severe allergy or intolerance to contrast media, narcotics, sedatives, or atropine

- No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

- Not pregnant or nursing

- Fertile patients must use effective contraception


Biologic therapy:

- No more than 1 prior adjuvant immunotherapy regimen for colon cancer


- At least 6 months since prior adjuvant chemotherapy and recovered

- No more than 1 prior adjuvant chemotherapy regimen for colon cancer

- No prior hepatic arterial infusion chemotherapy

Endocrine therapy:

- Not specified


- At least 1 month since prior radiotherapy

- No prior hepatic radiotherapy


- At least 1 month since prior surgery

- Prior surgical resection or ablation of liver metastases allowed


- No other concurrent therapy

Geschlecht: All

Mindestalter: 18 Years

Maximales Alter: N/A

Gesunde Freiwillige: No

Insgesamt offiziell
Nachname Rolle Zugehörigkeit
Michael C. Soulen, MD Study Chair Abramson Cancer Center of the University of Pennsylvania
Arizona Cancer Center | Tucson, Arizona, 85724, United States
H. Lee Moffitt Cancer Center and Research Institute | Tampa, Florida, 33612-9497, United States
Robert H. Lurie Comprehensive Cancer Center, Northwestern University | Chicago, Illinois, 60611-3013, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland, 21231-2410, United States
Beth Israel Deaconess Medical Center | Boston, Massachusetts, 02215, United States
NYU School of Medicine's Kaplan Comprehensive Cancer Center | New York, New York, 10016, United States
State University of New York - Upstate Medical University | Syracuse, New York, 13210, United States
University of Pennsylvania Cancer Center | Philadelphia, Pennsylvania, 19104-4283, United States
University of Texas - MD Anderson Cancer Center | Houston, Texas, 77030-4009, United States
Standort Länder

United States


December 2003

Hat den Zugriff erweitert No
Bedingung Durchsuchen
Studiendesign Info

Zuweisung: Randomized

Hauptzweck: Treatment