Clinical trial NCT00668512: Intratumoral Injection Of Alpha-Gal Glycosphingolipids
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Melanoma
Keywords: metastatic cutaneous melanoma
alpha-gal glycolipids
Lead sponsor: University of Massachusetts, Worcester
Sponsor class: OTHER
First posted: 2008-04-29
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

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.

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 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.

Primary outcomes:
measure: Grade 3/4 toxicity
timeFrame: 11-12 weeks
Secondary outcomes:
measure: Clinical response
timeFrame: 2 years
Other outcomes:
measure: Immune response in injected lesion
timeFrame: six weeks
Locations:
city: Madison
country: United States
facility: Universiity of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Massachusetts, Worcester
name: Giles Whalen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.