RATIONALE: Drugs used in chemotherapy, such as dacarbazine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Recombinant interferon alfa-2b may interfere with the growth of tumor cells. Giving interferon alfa-2b together with dacarbazine may be an effective treatment for primary uveal melanoma. PURPOSE: This phase II trial is studying how well giving dacarbazine together with recombinant interferon alfa-2b works 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
38
Given subcutaneously (SC) 3 times a week for 24 weeks
Given IV on days 1 and 29
Correlative studies obtained prior to therapy, every 8 weeks while on therapy, and then every 6 months during follow-up
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States
Number of Patients With Disease-free Survival (DFS)
DFS will be calculated from the date treatment starts to the date of documented recurrence or death. It will be summarized using the method of Kaplan and Meier. Treatment will be considered relatively ineffective in this population if the underlying 2-year DFS is \<60%, whereas the combination will be considered promising if the underlying rate is \>80%.
Time frame: 5 years from time-of-enrollment
Number of Participants With Toxicity or Grade 4 Adverse Events Via CTCAE Version 3.0
Number of participants with toxicity as defined as an underlying risk of \>33% Grade 3 (non blood/bone marrow) or Grade 4 adverse events that are related to therapy, assessed by NCI CTCAE version 3.0
Time frame: up to 32 weeks from start of study
Changes in Plasma Biomarkers and Their Association With DFS
Plasma levels of these markers will be summarized at baseline and over time quantitatively and graphically. Specific regulators of immune escape and tumor cell invasion identified in uveal melanoma gene array studies will be measured. Peripheral blood cells and plasma will be analyzed for granulysin (a measure of natural killer cells (NK) activity), beta2-microglobulin, autotoxin, lysophosphatidic acid (a product of autotaxin), matrix metalloproteinase-7, tissue inhibitor of matrix metalloproteinase, and soluble E-cadherin.
Time frame: 5 yrs from start of treatment
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