Clinical trial NCT00110123: Intravenous or Hepatic Arterial Infusion of Fotemustine in Treating Patients With Unresectable Liver Metastases From Eye Melanoma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Intraocular Melanoma
Metastatic Cancer
Keywords: liver metastases
ciliary body and choroid melanoma, medium/large size
iris melanoma
extraocular extension melanoma
recurrent intraocular melanoma
metastatic intraocular melanoma
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2005-05-04
Enrollment: 171
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Duration of survival
Secondary outcomes:
measure: Progression-free survival
measure: Best response as assessed by RECIST criteria
measure: Duration of response
measure: Toxicity as assessed by CTCAE v3
Other outcomes:
Locations:
city: Milan
country: Italy
facility: European Institute of Oncology
city: Naples
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Siena
country: Italy
facility: Universita di Siena
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology - Warsaw
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: England
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
state: Scotland
Study officials:
affiliation: Centre Hospitalier Universitaire Vaudois
name: Serge Leyvraz, MD
role: STUDY_CHAIR
References:
citation: Leyvraz S, Piperno-Neumann S, Suciu S, Baurain JF, Zdzienicki M, Testori A, Marshall E, Scheulen M, Jouary T, Negrier S, Vermorken JB, Kaempgen E, Durando X, Schadendorf D, Gurunath RK, Keilholz U. Hepatic intra-arterial versus intravenous fotemustine in patients with liver metastases from uveal melanoma (EORTC 18021): a multicentric randomized trial. Ann Oncol. 2014 Mar;25(3):742-746. doi: 10.1093/annonc/mdt585. Epub 2014 Feb 7.
citation: Orcurto V, Denys A, Voelter V, Schalenbourg A, Schnyder P, Zografos L, Leyvraz S, Delaloye AB, Prior JO. (18)F-fluorodeoxyglucose positron emission tomography/computed tomography and magnetic resonance imaging in patients with liver metastases from uveal melanoma: results from a pilot study. Melanoma Res. 2012 Feb;22(1):63-9. doi: 10.1097/CMR.0b013e32834d3dcb.