Safety Study of Infusion of SGT-53 to Treat Solid Tumors
This is a Phase Ib study as a continuation of the original Phase I protocol. The purpose of this Phase Ib study is to evaluate the safety of a single course of SGT-53 in combination with docetaxel and determine the recommended Phase II doses of SGT-53 and docetaxel in combination for evaluation in subsequent clinical studies for the treatment of solid tumors.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Open-Label Safety and Pharmacokinetic Study of Escalating Doses of SGT-53 for Infusion in Subjects With Advanced Solid Tumors|
- Safety will be assessed by analysis of adverse experiences, clinical laboratory tests, and physical examinations. [ Time Frame: 7 weeks ] [ Designated as safety issue: Yes ]
- Pharmacokinetic parameters [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]Phase Ia Only
- Tumor Response [ Time Frame: Week 6 for Phase Ia, and weeks 9 for Phase Ib ] [ Designated as safety issue: No ]Assessed by physical measurements or by radiographic modalities
- Determine the presence of exogenous wtp53 in tumor [ Time Frame: Week 5 or Week 6 ] [ Designated as safety issue: No ]
|Study Start Date:||February 2008|
|Estimated Study Completion Date:||August 2015|
|Estimated Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
SGT-53 (2.4mg DNA/infusion) will be administered in a standard 3x3 dose escalation design in combination with docetaxel 40mg/m2 starting dose, cohort 1, cycle 1. This protocol will allow for both inter- and intra-patient dose escalations. SGT-53 will be administered weekly, day 1 except weeks 1, 4 & 7 when it will be administered biweekly on days 1 & 4. Docetaxel will be administered every 3 weeks (weeks 1, 4 & 7) on day 3. Patients completing cohort 1, cycle 1 without DLT at docetaxel 40mg/m2 will be allowed to dose escalate to 60mg/m2 in cycles 2 and 3. Cohort 2 (2.4mg DNA/infusion;75mg/m2 Docetaxel) will open 3 weeks after demonstration of 0/3 or ≤1/6 DLTs at docetaxel 60mg/m2. Cohort 3 (3.6mg DNA/infusion; 75mg/m2 Docetaxel) will open after demonstration of 0/3 or ≤1/6 DLTs at SGT-53 2.4mg DNA/infusion and docetaxel 75mg/m2. If necessary, the dose of docetaxel in cycle 2 and 3 may be reduced to 60mg/m2.
For Phase Ib: SGT-53 (2.4 mg DNA per infusion) will be administered in combination with docetaxel at 40 mg/m2 starting dose, cohort 1, cycle 1. SGT-53 will be administered weekly, on day 1 in weeks 2, 3, 5, and 6, and biweekly on days 1 and 4 in weeks 1, 4, and 7. Docetaxel will be administered every 3 weeks (weeks 1, 4, and 7)on day 3. Patients completing cohort 1, cycle 1 without DLT at 40 mg/m2 docetaxel will be allowed to dose escalate to 60 mg/m2 docetaxel in cycles 2 and 3.Cohort 2 (2.4mg DNA/infusion;75mg/m2 Docetaxel) will open 3 weeks after demonstration of 0/3 or ≤1/6 DLTs at docetaxel 60 mg/m2. Cohort 3 (3.6 mg DNA/infusion; 75 mg/m2 Docetaxel) will open after demonstration of 0/3 or ≤1/6 DLTs at SGT-53 2.4 mg DNA/infusion and docetaxel 75 mg/m2.
The p53 gene is a vital tumor suppressor gene in humans. Numerous human tumors possess a loss or mutation of wild type p53 (wtp53). In addition to playing a crucial role in cell cycle control, the p53 gene is a critical component in two of the pathways involved in regulating tumor cell growth: cell death (apoptosis) and the regulation of angiogenesis. The loss of such critical tumor suppressor activity is believed to be responsible for p53's involvement in such a broad array of human tumors and resistance to chemo/radiotherapy. SGT-53 is a complex composed of a wild type p53 gene (plasmid DNA) encapsulated in a liposome that is targeted to tumor cells by means of an anti-transferrin receptor single-chain antibody fragment (TfRscFv) attached to the outside of the liposome. Pre-clinical studies have indicated that SGT-53 could sensitize tumors to the effects of radiation/chemotherapy.
The Phase 1a portion of this clinical study was designed to evaluate the safety and maximum tolerated dose (MTD) of SGT-53. In addition, pharmacokinetics of escalating doses of SGT-53 will be measured and correlated with tumor response and toxicity.
The Phase Ib portion of this clinical study is designed to evaluate the safety of SGT-53 in combination with docetaxel, determine the recommended Phase II doses of these two agents, and evaluate the effect of the combination of SGT-53 and docetaxel on tumor size or progression.
|United States, Texas|
|Mary Crowley Medical Research Center|
|Dallas, Texas, United States, 75201|
|Principal Investigator:||John J. Nemunaitis, MD||Mary Crowley Medical Research Center|