Pegylated Arginine Deiminase in Treating Patients With Metastatic Melanoma That Cannot Be Removed by Surgery

Study Overview
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Brief Summary
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RATIONALE: Pegylated arginine deiminase may stop the growth of tumor cells by taking away an amino acid needed for cell growth. PURPOSE: This phase II trial is studying how well pegylated arginine deiminase works in treating patients with metastatic melanoma that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Primary: Determine the clinical response (complete and partial response) in patients with unresectable metastatic melanoma treated with pegylated arginine deiminase. Secondary: Determine the toxicity profile of this drug in these patients. Determine the pharmacokinetics and pharmacodynamics of this drug in these patients. Determine the progression-free survival and overall survival of patients treated with this drug. OUTLINE: Patients receive pegylated arginine deiminase intramuscularly once or twice a week in weeks 1-4. Courses repeat every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Blood samples are acquired at baseline and every 2 weeks thereafter for pharmacokinetic and pharmacodynamic studies. After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 5 years, and annually thereafter. PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.

Official Title
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Clinical Protocol for Phase II Testing of ADI-PEG 20 in Patients With Metastatic Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: ADI-PEG-20
* Other: Pharmacology Studies


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed metastatic melanoma, meeting any of the following criteria: Progressive disease after chemotherapy, radiotherapy, surgery, or immunotherapy No longer responding to standard therapy OR have refused standard therapy Unresectable disease Measurable or evaluable disease No clinical ascites No symptomatic pleural effusion PATIENT CHARACTERISTICS: Life expectancy ≥ 12 weeks Karnofsky performance status 70-100% Bilirubin ≤ 3.0 mg/dL Albumin ≥ 3.0 g/dL Alkaline phosphatase < 5 times upper limit of normal (ULN) Serum glucose > 60 mg/dL Amylase < 1.5 times ULN Absolute neutrophil count > 1,500/mm³ Platelet count > 100,000/mm³ No New York Heart Association class III-IV heart failure No serious infection requiring treatment with antibiotics No known allergy to E. coli drug products (e.g., sargramostim [GM-CSF]) Not pregnant or nursing Negative pregnancy test Fertile patients must use 2 forms of effective contraception PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 4 weeks since prior anticancer therapy At least 4 weeks since prior surgery and recovered No concurrent participation in another investigational drug study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: ADI-PEG 20<br> | Biological: ADI-PEG-20<br>* There will be 6 cycles planned, each consisting of 4 weeks. During each cycle subjects will receive injections on days 1, 8, 15, and 22 + 2 days. All subjects may begin treatment with 160 IU/m2 on a weekly basis.<br>* Other names: Arginine Deiminase (ADI) formulated with polyethylene glycol (PEG);Other: Pharmacology Studies<br>* tissue blocks will be obtained from the initial biopsy of melanoma. Immunohistochemical staining for ASS and RT-PCR will be performed on the tumor tissue<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate (Partial and Complete Response) in Patients With or Without ASS Expression Present in Tumor. | Response rate is defined as a partial response, PR, and complete response, CR, lasting for at least 30 days per RECIST criteria, v. 1.0. Complete response will be defined as disappearance of all target lesions. Partial response will be defined as at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference the baseline sum of LD | Up to 16 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Overall Survival | Overall survival will be estimated using the product-limit method of Kaplan & Meier. | Up to 16 months | 
| Median Time to Progression | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | Up to 16 months | 

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