Combination Chemotherapy With or Without Chemoembolization in Treating Patients With Colorectal Cancer Metastatic to the Liver (6655)

Sponsor

American College of Radiology Imaging Network (Other)

Overall Status

Terminated

CT.gov ID

NCT00023868

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

10.8

Actual Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Metastatic Cancer	Drug: FOLFIRI regimen Drug: cisplatin Drug: doxorubicin hydrochloride Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium Drug: mitomycin C	Phase 3

Detailed Description

OBJECTIVES:

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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 1, 2001

Actual Primary Completion Date :

Sep 25, 2002

Actual Study Completion Date :

Sep 25, 2002

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

Zubrod 0-2

Life expectancy:

Not specified

Hematopoietic:

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

Hepatic:

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

Renal:

Creatinine no greater than 2.0 mg/dL

Cardiovascular:

No myocardial infarction within the past 6 months
No evidence of congestive heart failure
No severe peripheral vascular disease that would preclude catheterization

Other:

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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No more than 1 prior adjuvant immunotherapy regimen for colon cancer

Chemotherapy:

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

Radiotherapy:

At least 1 month since prior radiotherapy
No prior hepatic radiotherapy

Surgery:

At least 1 month since prior surgery
Prior surgical resection or ablation of liver metastases allowed

Other:

No other concurrent therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Cancer Center	Tucson	Arizona	United States	85724
2	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612-9497
3	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois	United States	60611-3013
4	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
5	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
6	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York	United States	10016
7	State University of New York - Upstate Medical University	Syracuse	New York	United States	13210
8	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania	United States	19104-4283
9	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030-4009