Metastatic Melanoma
Conditions
Keywords
metastatic cutaneous melanoma, alpha-gal glycolipids
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.
Interventions
BIOLOGICALAntimelanoma 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.
Sponsors
University of Massachusetts, Worcester
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Grade 3/4 toxicity | 11-12 weeks | Grade 3/4 toxicity or adverse event during injection protocol or up to a month after |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical response | 2 years | Injected tumor deposit regression (RECIST), regression of other known metastases (RECIST), progression of disease (new metastases) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Immune response in injected lesion | six weeks | Evidence of immune cell infiltration of injected tumor: histologic comparison of biopsy of injected lesion with pre injection biopsy of same lesion |
Countries
United States
Outcome results
None listed