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

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.

Study Overview

• Status: Completed
• Conditions: Melanoma (Skin)
• Intervention / Treatment: Biological: ADI-PEG-20; Other: Pharmacology Studies

Detailed Description

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
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Sylvester Comprehensive Cancer Center - Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 118 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Miami
• Investigators: Study Chair: Lynn G. Feun, MD, University of Miami Sylvester Comprehensive Cancer Center

Publications and helpful links

General Publications

• Feun LG, Marini A, Walker G, Elgart G, Moffat F, Rodgers SE, Wu CJ, You M, Wangpaichitr M, Kuo MT, Sisson W, Jungbluth AA, Bomalaski J, Savaraj N. Negative argininosuccinate synthetase expression in melanoma tumours may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase. Br J Cancer. 2012 Apr 24;106(9):1481-5. doi: 10.1038/bjc.2012.106.

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: March 20, 2007
• First Submitted That Met QC Criteria: March 20, 2007
• First Posted (Estimate): March 22, 2007

Study Record Updates

• Last Update Posted (Estimate): February 8, 2017
• Last Update Submitted That Met QC Criteria: December 14, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: recurrent melanoma; stage IV melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: 20030698; SCCC-2003045