Dacarbazine and Recombinant Interferon Alfa-2b in Treating Patients With Primary Uveal Melanoma With Genetic Imbalance

PRIMARY OBJECTIVES:

I. Assess disease-free survival (DFS) with sequential dacarbazine and interferon-alfa-2b as
an adjuvant to primary therapy for patients with uveal melanoma with genetic imbalance.

SECONDARY OBJECTIVES:

I. Evaluate side effects and assess safety in the patient population.

II. Examine the relationship between the levels of plasma biomarkers of immune function and
tumor invasion and the clinical outcome.

OUTLINE: Patients receive dacarbazine IV on days 1 and 29. Beginning 4 weeks after the second
dose of dacarbazine, patients receive recombinant interferon alfa-2b subcutaneously 3 times a
week for 24 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months.

Inclusion

- Patients must have a diagnosis, either cytologic or histologic, of melanoma of the
iris, ciliary body and/or choroid

- Patient's tumor must exhibit monosomy 3 and/or 8q amplification as determined by
karyotype, comparative genomic hybridization (CGH), polymerase chain reaction
(PCR)-based microsatellite, and/or Fluorescence in situ Hybridization (FISH) analysis;
tissue or cells for analysis can be obtained at enucleation, resection, or by fine
needle aspirate (FNA).

- Patients must have undergone adequate primary therapy; this can include enucleation,
brachytherapy, proton beam radiotherapy, stereotactic irradiation, trans-scleral local
resection, transretinal resection or diode laser thermotherapy

- Patients must have had chest X-ray and hepatic ultrasound or other imaging methods
such as CT or MRI to eliminate distant disease

- Patients must have a performance status (ECOG) of < 2

- Patients must be entered within 56 days of completing primary therapy

- White blood count (WBC) ≥ 3.0 x 10^9/L

- Neutrophils ≥ 1.5 x 10^9/L

- Platelets ≥ 100 x 10^9/L

- international normalized ratio (INR) and partial thromboplastin time (PTT) < 1.5 x
upper limit of normal

- Hemoglobin ≥ 10 gm/100 ml

- Creatinine ≤ 2 mg/dl

- Bilirubin (total) ≤ 1.5 mg/dl

- Alanine transaminase (ALT) ≤ 1.5 x upper limit of normal

- Alkaline phosphatase ≤ 1.5 x upper limit of normal

- Aspartate aminotransferase (AST) ≤ 1.5 x upper limit of normal

- Patients must not have received any other systemic therapy for melanoma

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control) prior to study entry and for the
duration of study participation; should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating physician
immediately

- All patients must be informed of the investigational nature of this study and must
provide written informed consent in accordance with institutional and federal
guidelines; a copy of the informed consent document signed by the patient must be
given to the patient

Exclusion

- Patients with metastasis

- Patients that are pregnant or breastfeeding

- Patients may not be receiving any other investigational agents

- Patients with a history of immunodeficiency or autoimmune diseases are not eligible;
patients requiring therapy with corticosteroids or other immunosuppressives are not
eligible; patients requiring ongoing replacement therapy with physiologic doses of
corticosteroids will be eligible.

- Patients with uncontrolled intercurrent illness including, but not limited to ongoing
or active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements are not eligible

- Patients who are known to be positive for HIV or Hepatitis B Surface Antigen (HepBAg)

- No patient may have had a malignancy other than a malignant melanoma, with the
following exceptions: basal or squamous cell carcinomas of the skin; carcinoma in-situ
of the uterine cervix; any malignancy treated with curative intent and in complete
remission for > 3 years

- Patients with organ allografts