Intratumoral Injection Of Alpha-Gal Glycosphingolipids

NCT00668512 | Completed Phase 1 DMC

• 1 other identifier: UM200701
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Melanoma

Keywords

metastatic cutaneous melanoma; alpha-gal glycolipids

Outcome Measures

Primary Outcomes (1)

• Grade 3/4 toxicity

  Grade 3/4 toxicity or adverse event during injection protocol or up to a month after

  11-12 weeks

Secondary Outcomes (1)

• Clinical response

  2 years

Other Outcomes (1)

• Immune response in injected lesion

  six weeks

Study Arms (1)

Antimelanoma injection-GSL alpha-Gal

EXPERIMENTAL

Intervention consists of injection of a single melanoma metastasis with two injections of GSL alpha-Gal separated by four weeks. Both injections done with the same dose of GSL alpha-GAL each time. Phase 1 dose escalating scheme: 0.1mg, 1 mg, 10mg

Biological: Antimelanoma injection of GSL alpha-Gal

Interventions

Antimelanoma injection of GSL alpha-Gal BIOLOGICAL

Single arm, phase 1 trial of escalating doses of GSL alpha-Gal (0.1mg, 1mg, 10mg)injected into a melanoma metastasis at day 0 and then again 4 weeks later.

Also known as: Alph-Gal Glycosphingolipids

Antimelanoma injection-GSL alpha-Gal

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (Eastern Cooperative Oncology Group) performance of \<2. International Normalized Ratio (INR)\<1.5 and a PTT (partial thromboplastin time ) 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: (White Blood Cell Count) WBC \> 3500/mm3 or (absolute neutrophil count) 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Massachusetts, Worcester: lead

Study Sites (1)

Universiity of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (3)

• Malmberg KJ. Effective immunotherapy against cancer: a question of overcoming immune suppression and immune escape? Cancer Immunol Immunother. 2004 Oct;53(10):879-92. doi: 10.1007/s00262-004-0577-x. Epub 2004 Jul 28.

  PMID: 15338206 BACKGROUND

• 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. doi: 10.1016/j.coi.2003.09.018.

  PMID: 14630209 BACKGROUND

• 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. doi: 10.4049/jimmunol.174.12.7516.

  PMID: 15944250 RESULT

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Giles Whalen, MD

  University of Massachusetts, Worcester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 25, 2008
• First Posted: April 29, 2008
• Study Start: March 1, 2007
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: March 19, 2015

Record last verified: 2015-03

Locations

US (1)