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

University of Miami38 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Melanoma (Skin)

Interventions

ADI-PEG-20BIOLOGICAL

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.

Pharmacology StudiesOTHER

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 120 Years

Medical Language ↔ Plain English

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

Locations (1)

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, United States

Outcomes

Primary Outcomes

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

Time frame: Up to 16 months

Secondary Outcomes

Median Overall Survival

Overall survival will be estimated using the product-limit method of Kaplan \& Meier.

Time frame: 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

Time frame: Up to 16 months

Data from ClinicalTrials.gov

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