Evaluate The Toxicity And Feasibility Of Intra-Tumoral Injection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00668382
Recruitment Status : Completed
First Posted : April 29, 2008
Results First Posted : November 26, 2012
Last Update Posted : May 15, 2013
Information provided by (Responsible Party):
Giles Whalen, University of Massachusetts, Worcester

April 25, 2008
April 29, 2008
October 25, 2012
November 26, 2012
May 15, 2013
July 2007
July 2011   (Final data collection date for primary outcome measure)
Number of Subjects With Greater Than Grade 3 or 4 Toxicity [ Time Frame: 1 month ]
Grade 3/4 Toxicity occurring in a participant within a month of intratumoral injection
Destruction of visible metastases [ Time Frame: 11-12 weeks ]
Complete list of historical versions of study NCT00668382 on Archive Site
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Induction of an immune response that will destroy invisible micrometastases. [ Time Frame: 11-12 weeks ]
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Evaluate The Toxicity And Feasibility Of Intra-Tumoral Injection
Phase I Study To Evaluate The Toxicity And Feasibility Of Intra-Tumoral Injection Of Alpha-Gal Glycosphingolipids In Patients With Advanced Or Refractory Solid Tumors
This is a Phase I pilot study to evaluate the toxicity and feasibility of intratumoral injection (Glycosphingolipids) GSL alpha-GAL (beta-galactosidase) 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.
Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Neoplasm Metastases
Biological: Alpha-Gal Glycosphingolipid
Intra-tumoral injection of Alpha-Gal Glycosphingolipid to evaluate toxicity
Experimental: Alpha-Gal Glycosphingolipid injection
Intervention: Intratumoral injection of a single dose of Alpha-Gal Glycosphingolipid (0.1 mg,1mg, 10mg)
Intervention: Biological: Alpha-Gal Glycosphingolipid

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
July 2011
July 2011   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  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 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 equal or over 18 years old.
  6. ECOG (Eastern Cooperative Oncology Group ) performance of less than 2. (International Normalized Ratio) INR less than 1.5 and a (Partial Thromboplastin Time) 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: (White Blood Cell Count) WBC equal or above 3500/millimeter-cubed or (Absolute Neutrophil Count) 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.

Exclusion Criteria:

  1. Patients who are pregnant (as determined by a positive serum HCG (Human Chorionic Gonadotropin) 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 consent form.
  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 clinical study.
Sexes Eligible for Study: All
18 Years to 75 Years   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
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Giles Whalen, University of Massachusetts, Worcester
University of Massachusetts, Worcester
Not Provided
Principal Investigator: Giles Whalen, MD University of Massachusetts, Worcester
University of Massachusetts, Worcester
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP