A PHASE I SAFETY AND TOLERABILITY TRIAL OF RADIOTHERAPY, ANDROGEN DEPRIVATION, AND INTRATUMORAL INJECTIONS OF AdGVEGR.TNF.11D (TNFeradeTM) FOR PATIENTS WITH LOCALLY ADVANCED PROSTATE CANCER
- Histological documented high-risk localized prostate cancer defined by clinical stage
>=T3 or Gleason score ≥8.
- Lack of distant metastases (including bone, liver, or extrapelvic lymph node
metastases) on standard CT and bone scanning. Patients with suspected or
histologically confirmed pelvic lymph node metastases are eligible.
- Normal organ function defined by:
- Hgb > 10 mg/dl (may be transfused or on erythropoietin);
- Platelets > 100,000/l;
- Absolute neutrophil count > 1500/l.
- Bilirubin < 1.5 mg/dl.
- AST and ALT < 1.5X upper limit of normal.
- Written signed informed consent.
- Absolute or relative contraindication to prostate radiotherapy including but not
limited to prior pelvic radiotherapy, active infectious or inflammatory colitis, and
inability to lay supine for daily radiation treatments.
- Requirement for ongoing antithrombotic treatment with coumadin or one of its
derivatives, heparin or one of its derivatives, or thrombin inhibitors. Low dose
aspirin for prevention of cardiovascular events is acceptable.
- Active vascular disease defined as a stroke, transient ischemic attack (TIA),
myocardial infarction, or any vascular procedure performed for ischemic disease
within the last 6 months.
- History of thrombosis (pulmonary embolism (PE) or deep vein thrombosis (DVT)) or
- Coagulopathy (INR>1.5, PTT ratio >1.5)
- Major surgery within the last 1 month (excludes minor superficial surgeries,
biopsies, or minimally invasive approaches).
- Chemotherapy or experimental medications within 4 weeks of study entry.
- Chronic treatment for greater than 6 months with oral steroids at doses above 10
mg/day prednisolone (or equivalent).
- Clinical evidence of active infection of any type.
- HIV-positive patients receiving combination anti-retroviral therapy.
- Other significant concurrent medical or psychiatric illness that would limit
compliance with study.
- Unwilling to use condoms or another barrier method of birth control for at least 8
weeks following the last dose of TNFerade™ Biologic and some form of birth control
for at least one year. -