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

September 20, 2012 updated by: European Organisation for Research and Treatment of Cancer - EORTC

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

171

Phase

Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Italy
- - Milan, Italy, 20141
    - European Institute of Oncology
  - Naples, Italy, 80131
    - Istituto Nazionale per lo Studio e la Cura dei Tumori
  - Padova, Italy, 35128
    - Azienda Ospedaliera di Padova
  - Siena, Italy, 53100
    - Università di Siena
Poland
- - Warsaw, Poland, 02-781
    - Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology - Warsaw
Switzerland
- - Lausanne, Switzerland, CH-1011
    - Centre Hospitalier Universitaire Vaudois
United Kingdom
- England
  - Merseyside, England, United Kingdom, CH63 4JY
    - Clatterbridge Centre for Oncology
- Scotland
  - Dundee, Scotland, United Kingdom, DD1 9SY
    - Ninewells Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: TREATMENT
Allocation: RANDOMIZED
Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Duration of survival

Secondary Outcome Measures

Outcome Measure
Progression-free survival
Duration of response
Best response as assessed by RECIST criteria
Toxicity as assessed by CTCAE v3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2005

Primary Completion (ACTUAL)

June 1, 2011

Study Registration Dates

First Submitted

May 3, 2005

First Submitted That Met QC Criteria

May 3, 2005

First Posted (ESTIMATE)

May 4, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

September 24, 2012

Last Update Submitted That Met QC Criteria

September 20, 2012

Last Verified

September 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

EORTC-18021
2004-002245-12 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.