Symptoms and General Pathology

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Melanoma

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Neuroectodermal Tumors, Primitive

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Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

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Skin Diseases

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Neuroepithelioma

Amino Acids

All Drugs and Chemicals

Arginine

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.

ADI-PEG-20

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

Pharmacology Studies

Lynn G. Feun, MD

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.

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

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

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

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

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

University of Miami

Single Arm

Age, Categorical

Age, Continuous

Gender

United States

Region of Enrollment

Of the 38 subjects enrolled, only 10 were ASS-positive and 17 were ASS-negative. The remaining 11 subjects, who declined pre-treatment biopsies, were not assessed.

Lynn Feun MD

Patients with Argininosuccinate Synthetase (ASS) expression present in tumor

ADI-PED 20: Argininosuccinate Synthetase Positive (ASS+)

Patients without Argininosuccinate Synthetase (ASS) expression present in tumor

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pegylated Arginine Deiminase in Treating Patients With Metastatic Melanoma That Cannot Be Removed by Surgery	NCT00450372	Melanoma (Skin)	ADI-PEG-20 Pharmacology St...	18 Years - 120 Years	University of Miami
Pegylated Arginine Deiminase in Treating Patients With Metastatic Melanoma That Cannot Be Removed by Surgery	NCT00450372	Melanoma (Skin)	ADI-PEG-20 Pharmacology St...	18 Years - 120 Years	University of Miami

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