Safety Study of Infusion of SGT-53 to Treat Solid Tumors

This study is currently recruiting participants.
Verified August 2012 by SynerGene Therapeutics, Inc.
Sponsor:
Information provided by (Responsible Party):
SynerGene Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT00470613
First received: May 4, 2007
Last updated: August 20, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Neoplasm
Genetic: SGT-53
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by SynerGene Therapeutics, Inc.:

Primary Outcome Measures:
  • Safety will be assessed by analysis of adverse experiences, clinical laboratory tests, and physical examinations. [ Time Frame: 7 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 6 and 14 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 ]

Estimated Enrollment: 12
Study Start Date: February 2008
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SGT-53
SGT-53 (2.4 mg DNA per infusion) and docetaxel will be administered in a standard 3 x 3 dose escalation design in combination with docetaxel 40 mg/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 and 7 when it will be administered biweekly on days 1 and 4. Docetaxel will be administered every 3 weeks (weeks 1, 4 and 7) on day 3. No subject will initiate therapy until all preceding subjects have completed all first cycle study agent dose administrations. Patients completing cohort 1, cycle 1 without DLT at docetaxel 40 mg/m2 will be allowed to dose escalate to docetaxel 60 mg/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 60 mg/m2. A cycle is defined as one Docetaxel treatment within 3 weeks.
Genetic: SGT-53
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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have a biopsy confirmed diagnosis thereby providing histological diagnosis of a solid tumor malignancy.
  • Have been offered all standard or approved therapies for which they would be considered eligible and have specifically declined or decided to postpone.
  • Have solid tumors that can be measured on physical examination or by radiographic imaging studies.
  • Have a tumor for which docetaxel would be an appropriate therapeutic agent (Phase Ib only).
  • Patients (n=3) entered in phase Ib MTD dose expansion require biopsy accessible lesion in addition to measurable lesion and must consent to biopsy of tumor and normal skin.
  • Previous docetaxel allowed if > 6 months prior to study entry (Phase Ib only).
  • Be 18 years old or older.
  • Have an ECOG performance study of 0, 1 or 2 for Phase Ia, 0-1 for Phase Ib.
  • Be able to give informed consent.
  • Have recovered from any previous therapy side effects or toxicities prior to initiating protocol study infusions.
  • Have a life expectancy of more than 12 weeks.
  • Female subjects of childbearing potential must have a negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
  • Male and female subjects of reproductive potential must agree to use measures (e.g., condoms or birth control pills) to avoid pregnancy throughout the study and for 3 months following discontinuation of the study drug.
  • Organ function characterized by </= Grade 1 scores defined by CTCAE v3.0 unless, at the discretion of the investigator, the condition is not deemed to cause unacceptable risk to the patient. If deemed not to cause unacceptable risk to the patient, organ function of grade 2 is acceptable.
  • Laboratory values meeting the following criteria:

    • Hemoglobin >/= 10.0 gm/dL
    • Absolute neutrophil count > 1500/mm3
    • White blood cell count > 3000/mm3
    • Platelet count >/= 100,000/mm3
    • PT/PTT < 1.5 times the upper limit of normal
    • LDH </= 3 times the upper limit of normal and without clinical or laboratory evidence of DIC as determined by the clinical investigator
    • Total bilirubin </= 1.5 times the upper limit of normal (unless elevation is known to be due to Gilbert's Disease)
    • AST and ALT < 2.5 times the upper limit of normal withALP </= 2.5 x ULN
    • Creatinine </= 1.5 mg/dL or creatinine clearance >/= 50 ml/minute

Exclusion Criteria:

  • Have hematological malignancy
  • Prior hypersensitivity reaction to docetaxel (Phase Ib only)
  • Are pregnant or lactating women
  • Have signs and symptoms consistent with an active infection
  • Fever (> 38.1 C)
  • Treated with antibiotics for infection within one-week prior to study entry
  • Known HIV infection
  • Have any history of psychiatric disorders that would interfere with informed consent or follow-up.
  • Have any other concurrent disease that, in the judgment of the investigator, would contraindicate the administration of study drug or interfere with the study evaluations.
  • Have fasting glucose levels >/= 180 mg/dL.
  • Have diastolic blood pressure of > 90 mm Hg resting at baseline despite medication. (Acceptable if on hypertensive medication and diastolic blood pressure is </= 90 mm Hg.)
  • Have an abnormal stress echo or unfavorable results (at the discretion of the cardiologist) from the cardiac consultation and evaluation.
  • Have known cardiac disease, or a history of cardiac disease.
  • Had within six months prior to enrollment any of the following:

    • Cerebrovascular accident
    • Uncontrolled congestive heart failure (dyspnea on minimal exertion or while supine)
    • Unstable angina (chest pain greater than three times weekly while on therapy)
  • Have significant baseline neuropathies (>/= grade 2 based upon CTCAE v 3.0).
  • Requiring renal dialysis.
  • Receiving systemic steroids or other chronic immunosuppressive medications (e.g., tacrolimus, cyclosporine) within 30 days prior to study entry
  • Receiving hematopoietic growth factors
  • Receiving anticoagulants other than to maintain patency of venous access lines
  • Received an investigational drug within 30 days prior to study entry
  • Received radiation treatment < 4 weeks prior to study entry
  • Had prior exposure to gene vector delivery products
  • Received treatment with chemotherapeutic agents < 4 weeks prior to study entry except for mitomycin C or nitrosurea where subjects who received mitomycin C or nitrosoureas < 6 weeks prior to study entry are not eligible.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00470613

Contacts
Contact: Alyssa Roth 972-566-3061 aroth@marycrowley.org

Locations
United States, Texas
Mary Crowley Medical Research Center Recruiting
Dallas, Texas, United States, 75201
Contact: John J. Nemunaitis, MD    214-370-1870    jnemunaitis@marycrowley.org   
Contact: Cynthia Bedell, MSN RN ANP-C    214-370-1870    cbedell@marycrowley.org   
Principal Investigator: John J. Nemunaitis, MD         
Sub-Investigator: Neil N. Senzer, MD         
Sub-Investigator: Gerald Edelman, MD, PhD         
Sub-Investigator: James P. Pak, MD, DABR         
Sub-Investigator: Jairo R. Olivares, MD         
Sub-Investigator: Cynthia H. Bedell, MSN RN ANP-C         
Sub-Investigator: Cara East, MD         
Sub-Investigator: Minal Barve, MD         
Sub-Investigator: Henry Allen, MD         
Sub-Investigator: Kevin Y. Kim, MD         
Sub-Investigator: Cathy Hernandez, MD         
Sub-Investigator: Vidya Nandipati, MD         
Sub-Investigator: Jay Pudupakkam, MD         
Sub-Investigator: Anees J. Omar, MD         
Sub-Investigator: Kristen Casenave, MD         
Sub-Investigator: Swathi Bayya, MD         
Sponsors and Collaborators
SynerGene Therapeutics, Inc.
Investigators
Principal Investigator: John J. Nemunaitis, MD Mary Crowley Medical Research Center
  More Information

No publications provided

Responsible Party: SynerGene Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT00470613     History of Changes
Other Study ID Numbers: SGT53-01
Study First Received: May 4, 2007
Last Updated: August 20, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by SynerGene Therapeutics, Inc.:
Neoplasm

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on April 17, 2014