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)