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

Melanoma (Skin) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00450372
• Other study ID #: UMIAMI-20030698
• Secondary ID: SCCC-2003045
• Status: Completed
• Phase: Phase 2
• First received: March 20, 2007
• Last updated: July 25, 2014
• Start date: June 2004
• Est. completion date: February 2012

Study information

• Verified date: August 2013
• Source: University of Miami Sylvester Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: February 2012
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

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:
• 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

Locations

Country	Name	City	State
United States	University of Miami Sylvester Comprehensive Cancer Center - Miami	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Miami Sylvester Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 argin — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Median Overall Survival	Overall survival will be estimated using the product-limit method of Kaplan & Meier.	Up to 16 months	No
Secondary	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	No