Hepatic Arterial Infusion With Melphalan in Treating Patients With Unresectable Liver Cancer

National Cancer Institute (NCI)

Status and phase

Completed

Phase 1

Conditions

Metastatic Cancer

Liver Cancer

Treatments

Drug: melphalan

Drug: isolated perfusion

Study type

Interventional

Funder types

NIH

Identifiers

NCT00030082

NCI-01-C-0215

CDR0000068941

Details and patient eligibility

About

RATIONALE: Heating melphalan to several degrees above body temperature and infusing it to the affected area directly around the tumor may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of hepatic arterial infusion with melphalan in treating patients who have unresectable liver cancer.

Full description

OBJECTIVES:

Determine the dose-limiting toxicity and maximum tolerated dose of hepatic arterial infusion with melphalan in patients with unresectable liver cancer.
Determine the regional and systemic toxic effects of this drug in these patients.
Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients undergo percutaneous hepatic arterial infusion, using a double balloon catheter in the inferior vena cava to isolate circulation to the liver, with melphalan over 30 minutes on day 1. Treatment may be repeated when all toxic effects are grade 2 or less. Patients undergo staging at 4 weeks after completion of the second treatment. Patients may receive 2 additional treatments.

Cohorts of 3-6 patients receive escalating doses of melphalan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 12 additional patients are treated with melphalan at the recommended dose.

Patients are followed every 3 months for 2 years and then every 4 months for 1 year.

PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.

Sex

All

Ages

14+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed unresectable cancer of the parenchyma of the liver
Liver metastases allowed
Limited unresectable extrahepatic disease (including but not limited to the following) is allowed provided the life-threatening component of progressive disease is in liver:
- Up to 4 pulmonary nodules each less than 1 cm in diameter
- Retroperitoneal lymph nodes less than 3 cm in diameter
- Fewer than 10 skin or subcutaneous metastases less than 1 cm in diameter
- Asymptomatic bone metastases that have been or can be palliated with radiotherapy
- Solitary metastasis to any site that can be resected
Prior therapy with intrahepatic perfusion with or without hepatic arterial infusion with floxuridine is allowed provided patient had a radiographic partial response of 3-months duration

PATIENT CHARACTERISTICS:

Age:

14 and over

Performance status:

ECOG 0-2

Life expectancy:

Not specified

Hematopoietic:

Platelet count greater than 100,000/mm^3
Absolute neutrophil count at least 1,300/mm^3
Hematocrit greater than 27%

Hepatic:

Bilirubin no greater than 2.0 mg/dL
PT within 2 seconds of upper limit of normal
No biopsy-proven cirrhosis with evidence of portal hypertension by history, endoscopy, or radiologic study

Renal:

Creatinine no greater than 1.5 mg/dL OR
Creatinine clearance greater than 60 mL/min

Cardiovascular:

No prior congestive heart failure with LVEF less than 40%

Pulmonary:

No chronic obstructive pulmonary disease
No other chronic pulmonary disease
FEV_1 at least 30% of predicted
DLCO at least 40% of predicted

Other:

Weight greater than 35 kg
HIV negative
No active infections
No severe allergic reaction to iodine contrast not controlled by antihistamines or steroids
No known prior hypersensitivity reaction to melphalan
Not pregnant or nursing
Negative pregnancy test

PRIOR CONCURRENT THERAPY:

Biologic therapy: