A Phase I Study of Systemic Gene Therapy With SGT-94 in Patients With Solid Tumors (SGT94-01)

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.