- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00668512
Intratumoral Injection Of Alpha-Gal Glycosphingolipids
Phase I Study To Evaluate The Toxicity And Feasibility Of Intratumoral Injection Of Alpha-Gal (Beta-galactosidase ) Glycosphingolipids In Patients With Advanced Melanoma
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Wisconsin
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Madison, Wisconsin, United States, 53792
- Universiity of Wisconsin
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 (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.
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.
Study Plan
How is the study designed?
Design Details
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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
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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 Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Grade 3/4 toxicity
Time Frame: 11-12 weeks
|
Grade 3/4 toxicity or adverse event during injection protocol or up to a month after
|
11-12 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical response
Time Frame: 2 years
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Injected tumor deposit regression (RECIST), regression of other known metastases (RECIST), progression of disease (new metastases)
|
2 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Immune response in injected lesion
Time Frame: six weeks
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Evidence of immune cell infiltration of injected tumor: histologic comparison of biopsy of injected lesion with pre injection biopsy of same lesion
|
six weeks
|
Collaborators and Investigators
Investigators
- Principal Investigator: Giles Whalen, MD, University of Massachusetts, Worcester
Publications and helpful links
General 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. doi: 10.4049/jimmunol.174.12.7516.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- UM200701
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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