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

NCT01517464 | Completed Phase 1 DMC

• 1 other identifier: SGT94-01
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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 evidence of RB94 expression within tumor tissue after systemic administration of SGT-94.

Conditions

Neoplasm

Keywords

neoplasm; bladder cancer; advances solid tumors

Outcome Measures

Primary Outcomes (1)

• Severity of Adverse Events

  The severity of adverse experiences in each patient will be determined based upon changes in the results of clinical laboratory tests and physical examnations. These findings will be used to determine the safety and tolerability of increasing doses of SGT-94.

  4 weeks each patient

Secondary Outcomes (3)

• Clinical Response

  Week 4

• Changes in Tumor Markers

  Week 4

• Expression of RB94 in Tumor Biopsies

  Week 2

Study Arms (1)

SGT-94

EXPERIMENTAL

Dose escalation of experimental therapeutic SGT-94 to assess safety

Genetic: SGT-94

Interventions

SGT-94 GENETIC

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.

SGT-94

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• SynerGene Therapeutics, Inc.: lead

Study Sites (1)

University of Texas, M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (4)

• Pirollo KF, Rait A, Zhou Q, Zhang XQ, Zhou J, Kim CS, Benedict WF, Chang EH. Tumor-targeting nanocomplex delivery of novel tumor suppressor RB94 chemosensitizes bladder carcinoma cells in vitro and in vivo. Clin Cancer Res. 2008 Apr 1;14(7):2190-8. doi: 10.1158/1078-0432.CCR-07-1951.

  PMID: 18381961 BACKGROUND

• Xu HJ, Xu K, Zhou Y, Li J, Benedict WF, Hu SX. Enhanced tumor cell growth suppression by an N-terminal truncated retinoblastoma protein. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9837-41. doi: 10.1073/pnas.91.21.9837.

  PMID: 7937901 BACKGROUND

• Xu HJ, Zhou Y, Seigne J, Perng GS, Mixon M, Zhang C, Li J, Benedict WF, Hu SX. Enhanced tumor suppressor gene therapy via replication-deficient adenovirus vectors expressing an N-terminal truncated retinoblastoma protein. Cancer Res. 1996 May 15;56(10):2245-9.

  PMID: 8625292 BACKGROUND

• Zhou J, Zhang XQ, Ashoori F, McConkey DJ, Knowles MA, Dong L, Benedict WF. Early RB94-produced cytotoxicity in cancer cells is independent of caspase activation or 50 kb DNA fragmentation. Cancer Gene Ther. 2009 Jan;16(1):13-9. doi: 10.1038/cgt.2008.54. Epub 2008 Jul 25.

  PMID: 18654611 BACKGROUND

MeSH Terms

Conditions

Neoplasms; Urinary Bladder Neoplasms

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Arlene Siefker-Radtke, M.D.

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2012
• First Posted: January 25, 2012
• Study Start: January 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: April 26, 2017

Record last verified: 2017-04

Locations

US (1)