Intratumoral Injection Of Alpha-Gal Glycosphingolipids

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Giles Whalen, University of Massachusetts, Worcester
ClinicalTrials.gov Identifier:
NCT00668512
First received: April 25, 2008
Last updated: March 19, 2014
Last verified: March 2014
  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: Antimelanoma injection of GSL alpha-Gal
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Phase I Study To Evaluate The Toxicity And Feasibility Of Intratumoral Injection Of Alpha-Gal (Beta-galactosidase ) Glycosphingolipids In Patients With Advanced Melanoma

Resource links provided by NLM:


Further study details as provided by University of Massachusetts, Worcester:

Primary Outcome Measures:
  • Grade 3/4 toxicity [ Time Frame: 11-12 weeks ] [ Designated as safety issue: Yes ]
    Grade 3/4 toxicity or adverse event during injection protocol or up to a month after


Secondary Outcome Measures:
  • Clinical response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Injected tumor deposit regression (RECIST), regression of other known metastases (RECIST), progression of disease (new metastases)


Other Outcome Measures:
  • Immune response in injected lesion [ Time Frame: six weeks ] [ Designated as safety issue: No ]
    Evidence of immune cell infiltration of injected tumor: histologic comparison of biopsy of injected lesion with pre injection biopsy of same lesion


Estimated Enrollment: 12
Study Start Date: March 2007
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Antimelanoma injection-GSL alpha-Gal
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
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.
Other Name: Alph-Gal Glycosphingolipids

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:

  1. Patients with recurrent melanoma who have failed standard therapies, or are not candidates for standard therapies.
  2. Patients must have at least one measurable cutaneous lesion that is accessible and suitable for injection of the GSL alpha-GAL.
  3. 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.
  4. Patients should be judged by the investigator to be able to undergo safely the procedure needed to inject the tumor with GSL alpha-GAL.
  5. Age >18 years old.
  6. 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)
  7. 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.
  8. Patients must be negative for HIV (circulating antibody), Hepatitis B (circulatory antigen), and Hepatitis C (circulating antibody).
  9. 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:

  1. Patients who are pregnant or nursing (PRN serum pregnancy test to be done at week -1).
  2. Patients under the age of 18.
  3. Patients with severe infections or septicemia.
  4. Patients with a history of autoimmune disease.
  5. Patients in, or about to be in, active treatment with chemotherapy or steroids.
  6. Patients who refuse HIV/hepatitis testing and patients who do not sign an approved consent form
  7. 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.
  8. Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Wisconsin
Universiity of Wisconsin
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
University of Massachusetts, Worcester
Investigators
Principal Investigator: Giles Whalen, MD University of Massachusetts, Worcester
  More Information

Publications:
Responsible Party: Giles Whalen, Principal Investigator, University of Massachusetts, Worcester
ClinicalTrials.gov Identifier: NCT00668512     History of Changes
Other Study ID Numbers: UM200701
Study First Received: April 25, 2008
Last Updated: March 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Massachusetts, Worcester:
metastatic cutaneous melanoma
alpha-gal glycolipids

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 July 23, 2014