This is a Phase I pilot study to evaluate the toxicity and feasibility of intratumoral
injection GSL alpha-GAL in patients with advanced, refractory solid tumors who have failed
standard therapies or are not eligible for standard treatment.
Intratumoral injection of alpha gal glycolipid in experimental knockout mouse model systems
incorporates into tumor cell membranes and presents these xeno-transplantation epitopes to
antigen presenting cells with that particular tumor's tumor associated antigens (TAA). Thus
this maneuver converts any individual tumor into an in situ tumor vaccine without the need
to isolate, purify or supply TAA exogenously. The effects in these model systems
demonstrate both the upregulation of cytotoxic T cells which react against the particular
tumor's TAA, as well as resolution of injected primary tumor and eradication and prevention
of metastatic disease at distant sites. This current study was undertaken to investigate
the safety and feasibility of such an approach in humans. The major toxicity concerns are
acute allergic or complement activation reactions or development of autoimmunity. The
primary treatment is a single intratumoral injection of alpha gal glycolipid. The study
design is a standard dose escalation design and the primary endpoint is Dose limiting
toxicity at one month after injection (grade 3 or 4. Subjects are followed until death
utilizing standard clinical imaging and evaluation to judge overall tumor response.
1. Patients with solid tumors who have failed standard therapies, or are not candidates
for standard therapies.
2. Patients must have at least one measurable 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 have
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
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 equal or over 18 years old.
6. ECOG performance of less than 2. INR less than 1.5 and a PTT no greater than normal
limits within 1 week prior to intra-tumoral injection (For patients who requires
invasive procedure for intra-tumoral injection).
7. Laboratory Criteria (completed equal or less 2 weeks before enrollment) Hematologic:
WBC equal or above 3500/millimeter-cubed or ANC equal or above 1500/millimeter-cubed
and platelet count equal or above 100,000/ millimeter-cubed.
Hepatic: Total bilirubin equal or less 4.0 milligrams/deciliter. Renal: Creatinine
equal or less 2.2 milligrams/deciliter.
8. Patients must be negative for HIV (circulating antibody), Hepatitis B (circulating
antigen), and Hepatitis C (circulating antibody).
9. Patients should have an expected survival of more than 6 weeks and should not have
other systemic anti-tumor treatments planned during this time frame.
1. Patients who are pregnant (as determined by a positive serum HCG in patients of
childbearing potential) or nursing.
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
7. Patient has received other investigational drugs within 14 days before enrollment or
is expected to participate in an experimental drug study during this study treatment.
8. Serious medical or psychiatric illness likely to interfere with participation in this