Intratumoral Injection Of Alpha-Gal Glycosphingolipids - Full Text View

Sponsor:	University of Massachusetts
Information provided by:	University of Massachusetts
ClinicalTrials.gov Identifier:	NCT00668512

Purpose

This is a Phase I pilot study to evaluate the toxicity of two intra-tumoral injections of GSL alpha-GAL in patients with advanced or metastatic cutaneous melanoma. Patients who have failed standard therapies or are not eligible for standard treatment will be eligible for this study.

Condition	Intervention	Phase
Metastatic Melanoma	Biological: Alpha-Gal Glycosphingolipids	Phase I

Study Type:	Interventional
Study Design:	Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Phase I Study To Evaluate The Toxicity And Feasibility Of Intratumoral Injection Of Alpha-Gal Glycosphingolipids In Patients With Advanced Melanoma

Resource links provided by NLM:

MedlinePlus related topics: Melanoma

U.S. FDA Resources

Further study details as provided by University of Massachusetts:

Primary Outcome Measures:

Destruction of visible metastases, and Induction of an immune response that will destroy invisible micrometastases. [ Time Frame: 11-12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	24
Study Start Date:	March 2007
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Injections of intra-tumoral GSL alpha-GAL to evaluate its toxicity & efficacy in a treatment modality to destroy such lesions and convert them into endogenous tumor vaccines by intratumoral injection of glycosphingolipids expressing alpha-gal epitope (designated GSL alpha-GAL).	Biological: Alpha-Gal Glycosphingolipids Injections of intra-tumoral GSL alpha-GAL to evaluate its toxicity & efficacy

Detailed Description:

A standard Phase I dose escalation model will be used to define the maximum tolerated dose (MTD) of GSL alpha-GAL that can be administered directly into the tumor lesion on two separate injections separated by 4-weeks. This trial will serve as the basis for future Phase II trials utilizing multiple injections of GSL alpha-GAL in refractory solid tumors.

Additionally, in this study we will look for histologic evidence of an immune response against the injected melanoma lesions which matches that seen in mice. Our hypothesis for this study is that a second injection of GSL alpha-GAL into a melanoma lesion will not precipitate an allergic or autoimmune reaction, but will cause a histologically evident immune response to the tumor.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with recurrent melanoma who have failed standard therapies, or are not candidates for standard therapies.
Patients must have at least one measurable cutaneous lesion that is accessible and suitable for injection of the GSL alpha-GAL.
Patients should not be undergoing any active treatment with chemotherapy, radiotherapy, or steroids (either because the patient or the treating physician has decided not to employ these therapies at this time, or because they had already been tried and failed). If they have been treated with these modalities, the treatments should have been completed at least two weeks prior to date of injection of GSL alpha-GAL.
Patients should be judged by the investigator to be able to undergo safely the procedure needed to inject the tumor with GSL alpha-GAL.
Age >18 years old.
ECOG performance of <2. INR<1.5 and a PTT no greater than normal limits within 1 week prior to intra-tumoral injection (For patients who may be on blood thinners)
Laboratory Criteria (completed <2 weeks before enrollment) Hematologic: WBC > 3500/mm3 or ANC > 1500/mm3 and platelet count > 100 000/ mm3 Hepatic: Total bilirubin < 4.0 mg/dl Renal: Creatinine < 2.2 mg/dl.
Patients must be negative for HIV (circulating antibody), Hepatitis B (circulatory antigen), and Hepatitis C (circulating antibody).
Patients should have an expected survival of >6 weeks and should not have other systemic anti-tumor treatments planned during this time frame.

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not eligible:

Patients who are pregnant or nursing (PRN serum pregnancy test to be done at week -1).
Patients under the age of 18.
Patients with severe infections or septicemia.
Patients with a history of autoimmune disease.
Patients in, or about to be in, active treatment with chemotherapy or steroids.
Patients who refuse HIV/hepatitis testing and patients who do not sign an approved consent form
Patient has received other investigational drugs within 14 days before enrollment or is expected to participate in an experiment drug study during this study treatment.
Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00668512

Contacts

Contact: Giles Whalen, MD	(508) 334-5052	Giles.Whalen@umassmemorial.org
Contact: Uri Galili, PhD	508-856-4188	Uri.Galili@umassmed.edu

Locations

United States, Massachusetts
Universiity of Massachusetts Medical School	Recruiting
Worcester, Massachusetts, United States, 01655
Principal Investigator: Giles Whalen, MD

Sponsors and Collaborators

University of Massachusetts

Investigators

Principal Investigator:

Giles Whalen, MD

Universtiy of Massachusetts Medical School

More Information

Publications:

Lugade AA, Moran JP, Gerber SA, Rose RC, Frelinger JG, Lord EM. Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J Immunol. 2005 Jun 15;174(12):7516-23.

Malmberg KJ. Effective immunotherapy against cancer: a question of overcoming immune suppression and immune escape? Cancer Immunol Immunother. 2004 Oct;53(10):879-92. Epub 2004 Jul 28. Review.

Spiotto MT, Fu YX, Schreiber H. Tumor immunity meets autoimmunity: antigen levels and dendritic cell maturation. Curr Opin Immunol. 2003 Dec;15(6):725-30. Review.

Responsible Party:	UMass Medical School ( Giles Whalen, MD )
Study ID Numbers:	UM200701
Study First Received:	April 25, 2008
Last Updated:	October 28, 2009
ClinicalTrials.gov Identifier:	NCT00668512 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Massachusetts:

metastatic cutaneous melanoma
alpha-gal glycolipids

Additional relevant MeSH terms:

Neuroectodermal Tumors
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue
Nevi and Melanomas
Neuroendocrine Tumors
Melanoma

ClinicalTrials.gov processed this record on February 08, 2010