ADI-PEG in Patients With Metastatic Melanoma

Phase I Testing of ADI-PEG in Metastatic Melanoma

This is a study to determine the safety and toxicity of increasing doses of arginine deiminase combined to polyethylene glycol (ADI-PEG) in patients with nonresectable metastatic melanoma.

Study Overview

• Status: Completed
• Conditions: Melanoma; Neoplasm Metastasis
• Intervention / Treatment: Drug: ADI PEG

Detailed Description

The use of amino acid degrading enzymes derived from microbial sources has proven to be an effective means of controlling some forms of cancer auxotrophic for nonessential amino acids. Recently it has been shown that human melanomas are auxotrophic for arginine. As arginine is a nonessential amino acid for humans, elimination of it may prove to be an effective method for controlling cancer. Laboratory studies have provided promising results with the arginine-degrading enzyme arginine deiminase (ADI) coupled to polyethylene glycol (PEG) to enhance its circulating half-life.

In this study, patients each receive 3 intramuscular treatments of ADI-SS PEG over a 4-week period. There are 4 cohorts of patients each receiving a different dose level. Pharmacokinetics, pharmacodynamics, safety and toxicity, and immunogenicity studies will be performed.

• Study Type: Interventional
• Enrollment: 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Histologically confirmed metastatic melanoma
• Nonresectable disease
• Measurable or evaluable disease
• Progressive disease following standard chemotherapy, radiotherapy, surgery, or immunotherapy; and no longer responding to therapy
• Recovered from prior surgery
• Karnofsky performance status 70 or higher
• Expected survival of at least 12 weeks
• Bilirubin less than 2.0 mg/dL
• Albumin greater than 3.0 g/dL
• SGOT less than 5 times upper limit of normal (ULN)
• Alkaline phosphatase less than 5 times ULN
• Ammonia less than 55 microg/dL
• Glucose greater than 60 mg/dL
• Amylase less than 1.5 times ULN
• Absolute neutrophil count greater than 1,500/mm3
• Platelet count greater than 100,000/mm3
• Patients must use 2 forms of effective contraception

Exclusion criteria:

• Prior therapy within the past 4 weeks
• Ascites or pleural effusion
• Significant cardiac disease (i.e., New York Heart Association class III or IV heart disease)
• Pregnant or nursing
• Concurrent enrollment in another IND study
• Serious infection requiring antibiotics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: FDA Office of Orphan Products Development

Study record dates

Study Major Dates

• Study Start: September 1, 2001
• Study Completion: August 1, 2003

Study Registration Dates

• First Submitted: January 24, 2002
• First Submitted That Met QC Criteria: January 24, 2002
• First Posted (Estimate): January 25, 2002

Study Record Updates

• Last Update Posted (Estimate): March 25, 2015
• Last Update Submitted That Met QC Criteria: March 24, 2015
• Last Verified: January 1, 2002

More Information

Terms related to this study

• Keywords: Dose-Response Relationship, Drug; Polyethylene Glycol; Arginine Deiminase
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplastic Processes; Neuroendocrine Tumors; Nevi and Melanomas; Neoplasm Metastasis; Melanoma
• Other Study ID Numbers: FD-R-2003-01; FD-R-002003-01