Intravenous or Hepatic Arterial Infusion of Fotemustine in Treating Patients With Unresectable Liver Metastases From Eye Melanoma

Metastatic Cancer Clinical Trial

Official title:

Intravenous Versus Intra-Arterial Fotemustine Chemotherapy in Patients With Liver Metastases From Uveal Melanoma: A Randomized Phase III Study of the EORTC Melanoma Group

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00110123
• Other study ID #: EORTC-18021
• Secondary ID: EORTC-180212004-
• Status: Terminated
• Phase: Phase 3
• First received: May 3, 2005
• Last updated: September 20, 2012
• Start date: January 2005

Study information

• Verified date: September 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as fotemustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving the drugs in different ways may kill more tumor cells. It is not yet known whether giving fotemustine as an intravenous infusion is more effective than giving it as a hepatic arterial infusion in treating liver metastases.

PURPOSE: This randomized phase III trial is studying intravenous infusion of fotemustine to see how well it works compared to hepatic arterial infusion of fotemustine in treating patients with unresectable liver metastases from eye melanoma.

Description:

OBJECTIVES:

Primary

• Compare overall survival of patients with surgically incurable or unresectable liver metastases secondary to uveal melanoma treated with fotemustine administered as an intravenous infusion vs an intra-arterial hepatic perfusion.

Secondary

• Compare progression-free survival of patients treated with this drug.

• Compare the response rate in patients treated with this drug.

• Compare the duration of objective response in patients treated with this drug.

• Compare the patterns of progression in patients treated with this drug.

• Compare treatment-related toxic effects and catheter-related complications in patients treated with this drug.

OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to participating center, lactic dehydrogenase level (normal vs abnormal), and WHO performance status (0 vs 1 vs 2). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive fotemustine IV over 1 hour on days 1, 8, and 15 (induction course). Beginning on day 50, patients receive maintenance courses of fotemustine IV over 1 hour every 21 days in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive fotemustine by a 4-hour intra-arterial (IA) hepatic perfusion on days 1, 8, 15, and 22 (induction course). Beginning on day 57, patients receive maintenance courses of fotemustine by a 4-hour IA hepatic perfusion every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 9 weeks for survival.

PROJECTED ACCRUAL: A total of 262 patients (131 per treatment arm) will be accrued for this study within 3 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 171
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed liver metastases secondary to uveal melanoma

• Surgically incurable or unresectable disease

• No detectable extrahepatic metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count = 2,000/mm^3

• Platelet count = 100,000/mm^3

• Hemoglobin = 10 g/dL

Hepatic

• Bilirubin < 1.5 times upper limit of normal (ULN)

• ALT and AST < 5 times ULN

• Alkaline phosphatase < 5 times ULN

• Gamma-glutamyltransferase < 5 times ULN

• Lactic dehydrogenase < 5 times ULN

Renal

• BUN < 1.5 times ULN

• Creatinine = 1.5 times ULN

Cardiovascular

• No uncontrolled angina pectoris

• No myocardial infarction within the past 6 months

• No uncontrolled high blood pressure

• No evolutive intracranial hypertension

• No other severe cardiac disease

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No active gastroduodenal ulcer

• No diabetes

• No active or uncontrolled infection

• No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up

• No other uncontrolled severe medical condition

• No other malignancy within the past 5 years except surgically cured carcinoma in situ of the cervix or basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunologic or biologic therapy

Chemotherapy

• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for metastatic disease

• No concurrent radiotherapy

Surgery

• Recovered from prior major surgery

Other

• No prior antineoplastic drugs for metastatic disease

• More than 4 weeks since prior investigational drugs

• No other concurrent anticancer agents or therapies

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Intraocular Melanoma
• Melanoma
• Metastatic Cancer
• Neoplasm Metastasis
• Uveal Neoplasms

Intervention

Drug:
• fotemustine

• isolated perfusion

Locations

Country	Name	City	State
Italy	European Institute of Oncology	Milan
Italy	Istituto Nazionale per lo Studio e la Cura dei Tumori	Naples
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Universita di Siena	Siena
Poland	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology - Warsaw	Warsaw
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
United Kingdom	Ninewells Hospital	Dundee	Scotland
United Kingdom	Clatterbridge Centre for Oncology	Merseyside	England

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Italy,  Poland,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of survival			No
Secondary	Progression-free survival			No
Secondary	Best response as assessed by RECIST criteria			No
Secondary	Duration of response			No
Secondary	Toxicity as assessed by CTCAE v3			Yes