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

American College of Radiology Imaging Network

Status and phase

Terminated

Phase 3

Conditions

Metastatic Cancer

Colorectal Cancer

Treatments

Drug: irinotecan hydrochloride

Drug: cisplatin

Drug: mitomycin C

Drug: FOLFIRI regimen

Drug: leucovorin calcium

Drug: doxorubicin hydrochloride

Drug: fluorouracil

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00023868

U01CA079778 (U.S. NIH Grant/Contract)

ACRIN-6655 (Other Identifier)

CDR0000068871

U01CA080098 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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: