Phase II Study of Combined Temozolomide and SGT-53 for Treatment of Recurrent Glioblastoma

Inclusion Criteria

• Histologically confirmed glioblastoma or gliosarcoma in 1st, 2nd or 3rd relapse.
• Radiographic demonstration of disease progression following prior therapy
• Measurable disease on MRI performed within 14 days prior to registration.
• Male or female patients ≥ 18 years of age.
• Recurrent disease with an:
• interval of ≥ 3 months following radiotherapy + TMZ;
• interval of ≥ 14 days between end of surgery and start of protocol therapy for patients who have undergone surgery for recurrent disease.
• Patients who tolerated previous administration with TMZ
• Recovery from the effects of prior therapy:
• 4 weeks from cytotoxic agents
• 6 weeks from nitrosoureas
• 4 weeks from any investigational agent
• 1 week from non-cytotoxic agents
• 12 weeks from radiotherapy
• Karnofsky performance status ≥ 60%.
• Complete blood count/differential at screening with adequate bone marrow function
• If patient is receiving steroids, must be on stable or decreasing steroid dose within 5 days prior to treatment initiation with SGT-53.
• Patients must be willing to forego other cytotoxic and non-cytotoxic drug or radiation therapy against the tumor while enrolled in the study.
• Women of childbearing potential must have a negative serum beta-HCG pregnancy test documented within 3 days prior to study initiation.
• Women of childbearing potential must agree to use two reliable methods of contraception from screening and up to 30 days after discontinuation of study treatment
• Males not naturally or surgically sterile, who have a female partner of childbearing potential, must agree to use two reliable methods of contraception from screening and up to 30 days after discontinuation of study treatment
• Acceptable liver function
• Acceptable blood sugar control
• Urinalysis: No clinically significant abnormalities.
• PT and PTT ≤ 1.5 X ULN
• Have recovered from any previous therapy side effects or toxicities
• Organ function characterized by ≤ Grade 1

Exclusion Criteria

• Histology other than astrocytoma grade IV
• Tumor foci detected below the tentorium or beyond the cranial vault.
• Glioblastoma or gliosarcoma disease with leptomeningeal spread.
• Patients with a history of any other cancer, unless in complete remission, and off all therapy for that disease for a minimum of 5 years
• Patients with serum aspartate aminotransferase, alanine aminotransferase > 2.5 X the upper limit of normal (ULN) and bilirubin >1.5 ULN
• Moderate to severe hepatic impairment.
• Positive results from HIV serology testing, if any available.
• Supine systolic blood pressure < 100 mmHg or supine diastolic blood pressure < 50 mmHg at screening and baseline
• Renal insufficiency or serum creatinine >1.5 X ULN at screening.
• Females who are pregnant or lactating or plan to become pregnant during the course of this study.
• Substance or alcohol abuse or dependence, within 12 months prior to screening.
• Prior chemotherapy for recurrent GBM with nitrosourea compounds including Gliadel® wafers or bevacizumab.
• Prior focal radiotherapy within 3 months of screening.
• Planned treatment, or treatment with any investigational drug within 4 weeks prior to screening.
• Severe, active co-morbidity
• Patients who are currently taking Coumadin or Coumadin derivatives other than to maintain patency of venous access lines.
• Requiring renal dialysis
• Receiving hematopoietic growth factors
• Have significant baseline neuropathies
• Had prior exposure to gene vector delivery products within 6 months
• Any condition that prevents compliance with the protocol or adherence to therapy.
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
• Treated with antibiotics for infection within one week prior to study entry.
• Fever (> 38.1°C)
• Have diastolic blood pressure of > 90 mm Hg resting at baseline despite medication.
• Serious nonmalignant disease
• Enrollment in a concomitant clinical study
• Have a history of hypersensitivity reaction to any of the components of Temozolomide
• Have a history of hypersensitivity to dacarbazine (DTIC)