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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00450372
Recruitment Status : Completed
First Posted : March 22, 2007
Results First Posted : May 1, 2013
Last Update Posted : February 8, 2017
Information provided by (Responsible Party):
University of Miami

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Melanoma (Skin) Biological: ADI-PEG-20 Other: Pharmacology Studies Phase 2

Detailed Description:



  • Determine the clinical response (complete and partial response) in patients with unresectable metastatic melanoma treated with pegylated arginine deiminase.


  • 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  (Clinical Trial)
Actual Enrollment : 38 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Clinical Protocol for Phase II Testing of ADI-PEG 20 in Patients With Metastatic Melanoma
Study Start Date : June 2004
Actual Primary Completion Date : January 2011
Actual Study Completion Date : February 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma
Drug Information available for: Arginine
U.S. FDA Resources

Arm Intervention/treatment
Experimental: ADI-PEG 20 Biological: ADI-PEG-20
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.
Other Name: Arginine Deiminase (ADI) formulated with polyethylene glycol (PEG)
Other: Pharmacology Studies
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

Primary Outcome Measures :
  1. Response Rate (Partial and Complete Response) in Patients With or Without ASS Expression Present in Tumor. [ Time Frame: Up to 16 months ]
    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

Secondary Outcome Measures :
  1. Median Overall Survival [ Time Frame: Up to 16 months ]
    Overall survival will be estimated using the product-limit method of Kaplan & Meier.

  2. Median Time to Progression [ Time Frame: Up to 16 months ]
    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

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00450372

United States, Florida
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami
Study Chair: Lynn G. Feun, MD University of Miami Sylvester Comprehensive Cancer Center

Publications of Results:
Responsible Party: University of Miami Identifier: NCT00450372     History of Changes
Other Study ID Numbers: 20030698
First Posted: March 22, 2007    Key Record Dates
Results First Posted: May 1, 2013
Last Update Posted: February 8, 2017
Last Verified: December 2016

Keywords provided by University of Miami:
recurrent melanoma
stage IV melanoma

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas