Clinical Trials /

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

NCT01517464

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

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

Title

  • Brief Title: A Phase I Study of Systemic Gene Therapy With SGT-94 in Patients With Solid Tumors
  • Official Title: A Phase I Study of Systemic Gene Therapy With SGT-94 in Patients With Solid Tumors
  • Clinical Trial IDs

    NCT ID: NCT01517464

    ORG ID: SGT94-01

    Trial Conditions

    Neoplasm

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    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.

    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 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 Arms

    Name Type Description Interventions
    SGT-94 Experimental Dose escalation of experimental therapeutic SGT-94 to assess safety

    Eligibility Criteria

    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 </= 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 Criteria:

    - 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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Severity of Adverse Events

    Secondary Outcome Measures

    Clinical Response

    Changes in Tumor Markers

    Expression of RB94 in Tumor Biopsies

    Trial Keywords

    neoplasm

    bladder cancer

    advances solid tumors