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

Phase 2

Completed

• Conditions: Iris Melanoma; Recurrent Intraocular Melanoma; Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size
• Interventions: Biological: recombinant interferon alfa-2b; Drug: dacarbazine; Other: laboratory biomarker analysis

• Registration Number: NCT01100528
• Lead Sponsor: Case Comprehensive Cancer Center

Brief Summary

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.

Detailed Description

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 Timeline

• Study Start: 2009-11-11
• Study First Submitted: 2010-04-07
• Study First Submitted QC: 2010-04-07
• Study First Posted: 2010-04-09
• Primary Completion: 2015-07-25
• Study Completion: 2017-12-14
• Results First Submitted: 2018-09-25
• Results First Submitted QC: 2018-09-25
• Results First Posted: 2018-10-29
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-11
• Last Update Posted: 2019-02-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	laboratory biomarker analysis	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.
Arm I	recombinant interferon alfa-2b	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.
Arm I	dacarbazine	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.

Primary Outcome Measures

Name	Time	Method
Number of Patients With Disease-free Survival (DFS)	5 years from time-of-enrollment	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%.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Toxicity or Grade 4 Adverse Events Via CTCAE Version 3.0	up to 32 weeks from start of study	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
Changes in Plasma Biomarkers and Their Association With DFS	5 yrs from start of treatment	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.

Trial Locations

Locations (1)

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center; 🇺🇸 Cleveland, Ohio, United States