Overview

This trial is active, not recruiting.

Condition neoplasm
Treatment sgt-94
Phase phase 1
Sponsor SynerGene Therapeutics, Inc.
Start date January 2012
End date December 2016
Trial size 24 participants
Trial identifier NCT01517464, SGT94-01

Summary

This is a Phase I study designed to evaluate the safety and maximum tolerated dose (MTD) of SGT-94, a novel, tumor-targeted, systemic gene therapy agent for cancer. In addition, we will look for evidence of RB94 expression within tumor tissue after systemic administration of SGT-94.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Dose escalation of experimental therapeutic SGT-94 to assess safety
sgt-94
SGT-94 will be given at doses of 0.6, 1.2, 2.4, 3.6 and 4.8 mgDNA/infusion(Doses 0-5, respectively)twice weekly for 3 weeks out of 4 in dose levels 0 to 4, and for 5 weeks out of 6 for dose level 5 (also 4.8mg DNA). Intravenous infusion will occur over 1 to 2.5 hours in 5% dextrose,with a final volume of SGT-94 and dextrose of 100 mL to 250 mL, depending on dose level.

Primary Outcomes

Measure
Severity of Adverse Events
time frame: 4 weeks each patient

Secondary Outcomes

Measure
Clinical Response
time frame: Week 4
Changes in Tumor Markers
time frame: Week 4
Expression of RB94 in Tumor Biopsies
time frame: Week 2

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histologic proof of cancer for which no standard therapy is available, and which shows no staining for RB by IHC. - Spirometry with at least 70% of predicted volumes (including FEV1). A left ventricular ejection fraction (LVEF) of 45% or more. All patients will have a screening 2-D Echocardiogram as part of eligibility screening. - Patients must have adequate physiologic reserve as evidenced by: - Zubrod Performance Status (PS) of /= 1,200/mm3 - Platelet count >100,000/mm3. - AST and ALT /= 10.0 g/dL without transfusion support - White blood cell count > 3.0 k/mm3 - PT and aPTT each < 1.5 times the upper limit of normal. - Women of child-bearing potential must have a negative pregnancy test. - Male and female patients reproductive potential must agree to use measures to avoid pregnancy throughout the study and for 3 months following discontinuing study drug. - Patients must have recovered from any previous therapy side effects or toxicities prior to initiating protocol study infusions. - Life expectancy > 12 weeks. - Organ function 140 or diastolic >90 despite therapy. - Serious concurrent psychiatric disorder that in the opinion of the investigator would compromise patient safety or preclude accurate assessment of outcome. - Supraphysiologic doses of glucocorticoids (defined as > 30 mg of hydrocortisone per day or > 7.5 mg of Prednisone per day, or equivalent doses of other agents) or exposure to other immunosuppressive medications in the previous 30 days. - Requirement for anticoagulant therapy other than low intensity treatment to maintain patency of central venous catheters. - Treatment with antibiotics for proven infection within 1 week prior to study entry or signs and symptoms consistent with an active infection or fever > 38.1 C.

Additional Information

Official title A Phase I Study of Systemic Gene Therapy With SGT-94 in Patients With Solid Tumors
Principal investigator Arlene Siefker-Radtke, M.D.
Description RB94, a tumor suppressor gene, is a modified form of the retinoblastoma gene, RB110. RB94 has shown enhanced tumor suppressor and tumor cell killing activity compared to RB110 in all tumor cell types studied to date, including bladder cancer cell lines. Moreover, RB94 has shown no toxicity to any normal human cells tested. SGT-94,the agent being tested, is a systemically administered complex composed of the RB94 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 in vivo efficacy studies have indicated that SGT-94, when systemically administered, preferentially targets tumor cells and efficiently transfects them. This results in cancer cell death via mechanisms that are unique for RB94 and also increases the tumor's response to conventional radiation and chemotherapy. This Phase I study is designed to evaluate the safety of SGT-94 and to establish a practically attainable and/or tolerable dose of this anti-cancer agent for use in further clinical trials. Additionally, evidence of RB94 expression within tumor tissue after systemic administration of SGT-94 will be sought, and clinically observable anti-cancer effects in patients will be documented. Enrollment will be targeted to individuals with "RB negative" tumors, i.e. tumors in which there is no staining for RB protein by immunohistochemistry (IHC). Preference will be given to patients with tumors in a location amenable to biopsy following treatment with SGT-94. This would include the prostate, bladder, superficial lymph nodes and any mass suitable for fine needle aspiration under CT or ultrasound guidance, or any lesion reachable by endoscopy.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by SynerGene Therapeutics, Inc..