Pegylated Arginine Deiminase in Treating Patients With Metastatic Melanoma That Cannot Be Removed by Surgery - Full Text View

Purpose

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	Intervention	Phase
Melanoma (Skin)	Biological: ADI-PEG-20 Other: Pharmacology Studies	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Clinical Protocol for Phase II Testing of ADI-PEG 20 in Patients With Metastatic Melanoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Arginine Arginine Hydrochloride

U.S. FDA Resources

Further study details as provided by University of Miami Sylvester Comprehensive Cancer Center:

Primary Outcome Measures:

Response Rate (Partial and Complete Response) in Patients With or Without ASS Expression Present in Tumor. [ Time Frame: Up to 16 months ] [ Designated as safety issue: No ]
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:

Median Overall Survival [ Time Frame: Up to 16 months ] [ Designated as safety issue: No ]
Overall survival will be estimated using the product-limit method of Kaplan & Meier.
Median Time to Progression [ Time Frame: Up to 16 months ] [ Designated as safety issue: No ]
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

Enrollment:	38
Study Start Date:	June 2004
Study Completion Date:	February 2012
Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Arms

Assigned Interventions

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

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00450372

Locations

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

Sponsors and Collaborators

University of Miami Sylvester Comprehensive Cancer Center

Investigators

Study Chair:

Lynn G. Feun, MD

University of Miami Sylvester Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

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.

Responsible Party:	University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00450372 History of Changes
Other Study ID Numbers:	EPROST-20030698, SCCC-2003045
Study First Received:	March 20, 2007
Results First Received:	February 1, 2013
Last Updated:	March 14, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Miami Sylvester Comprehensive Cancer Center:

recurrent melanoma
stage IV melanoma

Additional relevant MeSH terms:

Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on May 21, 2013