Status:

COMPLETED

A Phase I Study of Systemic Gene Therapy With SGT-94 in Patients With Solid Tumors

Lead Sponsor:

SynerGene Therapeutics, Inc.

Conditions:

Neoplasm

Eligibility:

All Genders

18+ years

Phase:

PHASE1

Brief 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 evide...

Detailed 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 ...

Eligibility Criteria

Inclusion

  • 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 \</= 2; or 3 if of recent onset (i.e. \< 2 weeks) and if the compromised performance status is related to uncontrolled pain which is expected to come under control by means of improved pain management.
  • Laboratory values meeting the following criteria:
  • Absolute neutrophil count \>/= 1,200/mm3
  • Platelet count \>100,000/mm3.
  • AST and ALT \</= 3x the upper limit of normal
  • Conjugated bilirubin \</= 1.5 mg/dL (or total bilirubin \</= 2.5 mg/dL)
  • Native kidney function producing creatinine clearance (either measured or estimated by Cockcroft formula) of at least 40 mL/min. Cockcroft formula: CLcr = \[(140-age) • wt(kg)\]/\[72 •Creat (mg/dL)\] (For females, multiply by 0.85)
  • Hemoglobin \>/= 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 \</= grade 1.
  • Age of \</= 18 years.

Exclusion

  • Some prior cancer therapies are not consistent with eligibility; specifically:
  • At least 30 days must have elapsed since any prior experimental therapy
  • At least 6 weeks must have elapsed since prior systemic mitomycin C
  • At least 8 weeks must have elapsed since any dose of Strontium-89
  • At least 4 weeks must have elapsed since prior Sm-153 lexidronam (Quadramet™)
  • At least 4 weeks must have elapsed since prior radiotherapy
  • Any prior exposure to gene vector delivery products
  • Pregnancy or lactation
  • Serious concurrent medical illness that in the opinion of the investigator would compromise patient safety or preclude accurate assessment of outcome.
  • Patients with the following manifestations of cardiovascular disease are excluded:
  • Myocardial infarction (MI) within the previous six months, or patients with left ventricular ejection fraction of less than 45% secondary to a more remote MI.
  • Any history of CVA or TIA in previous six months
  • New York Heart Association grade 2 or greater congestive failure
  • Unstable angina defined as angina (or anginal equivalent) 2 or more times per week despite medical therapy.
  • Echocardiographic evidence of pulmonary hypertension.
  • Diastolic dysfunction felt to contribute to any clinical sign or symptom.
  • Uncontrolled hypertension, defined as systolic BP \>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.

Key Trial Info

Start Date :

January 1 2012

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

December 1 2015

Estimated Enrollment :

13 Patients enrolled

Trial Details

Trial ID

NCT01517464

Start Date

January 1 2012

End Date

December 1 2015

Last Update

April 26 2017

Active Locations (1)

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1

University of Texas, M.D. Anderson Cancer Center

Houston, Texas, United States, 77030