PEG-Interferon Alfa-2b in Treating Patients With Stage IV Melanoma

Study Overview
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Brief Summary
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RATIONALE: Peginterferon (PEG-interferon) alfa-2b may stop the growth of cancer by stopping blood flow to the tumor. PURPOSE: Phase II trial to study the effectiveness of PEG-interferon alfa-2b in treating patients who have stage IV melanoma.

Detailed Description
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OBJECTIVES: Determine the ability of low-dose PEG-interferon alfa-2b to suppress plasma basic fibroblast growth factor (b-FGF) levels to normal in patients with metastatic melanoma over-expressing b-FGF. Determine the antitumor effect of this drug, in terms of progression-free and overall survival and tumor response, in these patients. Correlate tumor activity of this drug with b-FGF and vascular endothelial growth factor levels in the plasma and urine of these patients. Determine the safety profile of this drug in these patients. OUTLINE: This is a multicenter study. Patients receive PEG-interferon alfa-2b subcutaneously (SC) once weekly. Treatment continues until basic fibroblast growth factor level is suppressed to normal or until a maximum weekly dose is reached. If there is disease progression, patients then discontinue treatment. If there is no disease progression, patients receive PEG-interferon alfa-2b SC weekly for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 1 year. PROJECTED ACCRUAL: A total of 32 patients will be accrued for this study within 2 years.

Official Title
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Phase II Study of Low Dose Peginterferon Alfa-2b in Patients With Metastatic Melanoma Over-Expressing Basic Fibroblast Growth Factor

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: PEG-interferon alfa-2b


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Histologically confirmed stage IV melanoma Stage M1a, M1b, or M1c Mucosal, ocular, or unknown primary melanoma Previously untreated OR received up to 3 prior systemic therapy regimens (excluding vaccine therapy) for metastatic disease Plasma basic fibroblast growth factor level at least 15 pg/mL Measurable or evaluable disease Central nervous system (CNS) involvement allowed provided CNS directed therapy has been given and disease has been clinically stable for ≥ 3 months Brain computed tomography (CT) scan or Magnetic resonance imaging (MRI) to confirm stable disease required ≤ 4 weeks prior to study entry Age: 18 and over ECOG Performance status of 0-2 Life expectancy at least 6 months Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 8 g/dL (transfusions allowed) Bilirubin no greater than 2 times upper limit of normal (ULN) Alanine Aminotransferase (ALT) no greater than 2 times ULN Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 60 mL/min At least 4 weeks since prior interferon in the adjuvant or metastatic setting At least 4 weeks since prior chemotherapy in the adjuvant or metastatic setting At least 4 weeks since prior endocrine therapy in the adjuvant or metastatic setting At least 4 weeks since prior radiotherapy in the adjuvant or metastatic setting At least 4 weeks since prior surgery in the adjuvant or metastatic setting At least 4 weeks since other prior therapy in the adjuvant or metastatic setting Negative pregnancy test Fertile patients must use effective contraception Exclusion criteria: Myocardial infarction within the past 6 months Other active malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix Other concurrent illness that would preclude study participation History of severe depression Pregnant or nursing

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEG-interferon alfa-2b<br>Patients receive PEG-interferon alfa-2b subcutaneously (SC) once weekly. Treatment continues until basic fibroblast growth factor level is suppressed to normal or until a maximum weekly dose is reached. If there is disease progression, patients then discontinue treatment. If there is no disease progression, patients receive PEG-interferon alfa-2b SC weekly for up to 1 year in the absence of disease progression or unacceptable toxicity. | Biological: PEG-interferon alfa-2b<br>* Patients receive PEG-interferon alfa-2b subcutaneously (SC) once weekly. Treatment continues until basic fibroblast growth factor level is suppressed to normal or until a maximum weekly dose is reached. If there is disease progression, patients then discontinue treatment. If there is no disease progression, patients receive PEG-interferon alfa-2b SC weekly for up to 1 year in the absence of disease progression or unacceptable toxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma b-FGF Level Response | The primary endpoint was the suppression of plasma b-FGF level with low dose peginterferon alfa-2b. A clinically important reduction of plasma b-FGF levels was determined to be a level less than or equal to 7.5 pg/mL. A patient was considered to have a suppressed plasma b-FGF level, if the patient experienced the clinically significant reduction (less than or equal to 7.5 pg/mL) of plasma b-FGF levels for two consecutive determinations which were at least three weeks apart. This was considered as a b-FGF response. | assessed every 3 weeks until the suppression of plasma b-FGF level to normal, then every 6 weeks until the completion of 12 months of treatment, and upon treatment discontinuation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-progression Rate (Clinical Response to Peginterferon Alfa-2b) | Objective tumor response was assessed using RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria. Per RECIST criteria, complete response (CR) = disappearance of all target and non-target lesions. Partial response (PR)= >=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Progression is defined as at least 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s) or unequivocal progression of existing non-target lesions. Stable disease (SD) = did not meet criteria for response or progression. Non-progression rate = CR + PR + SD. | assessed every 9 weeks until suppression of plasma b-FGF level to normal, every 12 weeks until the completion of 12 months of treatment, >= 4 weeks after documented response. After off treatment, every 3 months if <2 years, and every 6 months if 2-3 years | 
| Progression Free Survival | Progression free survival (PFS) was defined as the time from registration to disease progression, or censored at last known date of non progressive disease. | assessed every 9 weeks until suppression of plasma b-FGF level to normal, every 12 weeks until the completion of 12 months of treatment, >= 4 weeks after documented response. After off treatment, every 3 months if <2 years, and every 6 months if 2-3 years | 
| Overall Survival | Overall survival (OS) time was defined as the time from registration to death from any cause, or censored at last known date of survival. | assessed every 3 months if <2 years, and every 6 months if 2-3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent melanoma, stage IV melanoma