GLIOBLASTOMA

To evaluate the 6 month PFS in patients treated with SGT-53 in combination with Temozolomide.

SGT-53

SGT-53

Vial (0.6mg/vial)

3.6mg

To evaluate the 6 month PFS in patients treated with SGT-53 in combination with Temozolomide.

1. Signed informed consent prior to any study-mandated procedure.
2. Histologically confirmed glioblastoma or gliosarcoma in first, second or third relapse. A pathology report constitutes adequate documentation of histology for study inclusion. Subjects with an initial diagnosis of a lower grade glioma are eligible if a subsequent biopsy is determined to be glioblastoma. The amount of prior systemic therapy for this population is, nevertheless, restricted to three regimens.
3. Radiographic demonstration of disease progression following prior therapy (RANO criteria)
4. Measurable disease on MRI performed within 14 days prior to registration. Baseline MRIs for subjects who underwent salvage surgery after first or second relapse must be obtained ≥ 4 weeks after the procedure.
5. Male or female patients ≥ 18 years of age.
6. Recurrent disease with an:
 interval of ≥ 3 months following radiotherapy + temozolomide;
 interval of ≥ 14 days between end of surgery and start of protocol therapy for patients who have undergone surgery for recurrent disease.

7. Patients who tolerated previous administration with temozolomide, i.e.,during adjuvant Temozolomide, no dose reductions below the starting dose were required due to treatment-related toxicities
8. Recovery from the effects of prior therapy, including the following:
• Four weeks from cytotoxic agents (3 weeks from procarbazine, 2 weeks from vincristine)
• 6 weeks from nitrosoureas (CCNU, BCNU)
• Four weeks from any investigational agent
• One week from non-cytotoxic agents
• 12 weeks from radiotherapy to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, or 4 weeks if a new lesion, relative to the pre-radiation MRI, develops that is outside the primary radiation field

9. Karnofsky performance status ≥ 60% (see Section 18.3. for details).
10. Complete blood count (CBC)/differential at screening (within 7 days of study initiation), with adequate bone marrow function as defined by: absolute neutrophil count (ANC) ≥ 1,500/μL; platelets ≥ 100,000/μL; hemoglobin ≥ 10 g/dL.
11. If patient is receiving steroids, must be on stable or decreasing steroid dose within 5 days prior to treatment initiation with SGT-53.
12. Patients must be willing to forego other cytotoxic and non-cytotoxic drug or radiation therapy against the tumor while enrolled in the study.
13. Women of childbearing potential must have a negative serum beta-HCG pregnancy test documented within 3 days prior to study initiation.
14. 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 (refer to Section 11.15 for further details).
• Reliable methods of contraception include intrauterine devices (IUD) or intrauterine systems (IUS), tubal sterilization, and barrier methods (male condom, diaphragm, or cervical cap). A female partner’s vasectomy still requires 1 additional method of contraception. Abstinence, the rhythm method, or contraception by the other partner alone, will not be considered as a reliable methods of contraception.

15. 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 (refer to Section 11.15. for further details).
16. Acceptable liver function (obtained within 7 days prior to registration):
 Bilirubin ≤ 1.5 times upper limit of normal (CTCAE Grade 1 baseline); Total bilirubin ≤3xULN with direct bilirubin within normal range in patients with well documented Gilbert’s syndrome
 AST (SGOT), ALT (SGPT) ≤ 2.5 x ULN (CTCAE Grade 1 baseline)
 Serum creatinine ≤ 1.5 X ULN (CTCAE Grade 1 baseline)
17. Acceptable blood sugar control (based on labs obtained within 7 days prior to registration): Fasting glucose value < 160 mg/dL (CTCAE Grade 1 baseline)
18. Urinalysis (obtained within 7 days prior to registration): No clinically significant abnormalities.
19. PT and PTT ≤ 1.5 X ULN after correction of nutritional deficiencies that may contribute to prolonged PT/PTT (obtained within 7 days prior to registration).

20. Have recovered from any previous therapy side effects or toxicities (to < grade 1, except alopecia) prior to initiating protocol study infusions.
21. Organ function characterized by ≤ Grade 1 scores defined by CTCAE v4.03 unless, at the discretion of the investigator, the condition is not deemed to cause unacceptable risk to the patient. If deemed not to cause unacceptable risk to the patient, organ function of grade 2 is acceptable.

1. Histology other than astrocytoma grade IV (GBM or gliosarcoma).
2. Tumor foci detected below the tentorium or beyond the cranial vault.
3. Glioblastoma or gliosarcoma disease with leptomeningeal spread.
4. 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 (except history of basal or squamous cell skin cancers that are completely excised/cured at time of enrollment).
5. Patients with serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 2.5 X the upper limit of normal (ULN) and bilirubin >1.5 ULN, (unless there is a medical justification for the elevation of bilirubin and ALT, AST).
6. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B/C.
7. Positive results from HIV serology testing, if any available.
8. Supine systolic blood pressure < 100 mmHg or supine diastolic blood pressure < 50 mmHg at screening and baseline, or documented medical history of orthostatic hypotension.
9. Renal insufficiency (estimated creatinine clearance < 50 mL/min) or serum creatinine >1.5 X ULN at screening.
10. Females who are pregnant or lactating or plan to become pregnant during the course of this study.
11. Substance or alcohol abuse or dependence, within 12 months prior to screening.
12. Prior chemotherapy for recurrent GBM with nitrosourea compounds including Gliadel® (carmustine) wafers or bevacizumab.
13. Prior focal radiotherapy (stereotactic radiotherapy or Gamma Knife) within 3 months of screening.
14. Planned treatment, or treatment with any investigational drug within 4 weeks prior to screening.
15. Severe, active co-morbidity, including: Cardiac disease – congestive heart failure class III/IV NYHA; unstable angina or new onset angina (began within the last 3 months) or acute or chronic myocardial infarction within the past 6 months; cardiac ventricular arrhythmias requiring anti-arrhythmic therapy; cerebrovascular accident within 6 months prior to enrollment; acute bacterial or fungal infection requiring intravenous antibiotics at the time of screening; chronic hepatitis B or C infection; chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of screening; hematological and bone marrow diseases. Severe malabsorption (defined as > 15% unintentional loss of body weight in the last 6 months prior to study enrollment), Major medical illnesses or psychiatric impairments that, in the investigator’s opinion, will prevent administration or completion of protocol therapy.
16. Patients who are currently taking Coumadin or Coumadin derivatives other than to maintain patency of venous access lines.
17. Requiring renal dialysis
18. Receiving hematopoietic growth factors
19. Have significant baseline neuropathies (> grade 2 based upon CTCAE v 4.03)
20. Had prior exposure to gene vector delivery products within 6 months
21. Any condition that prevents compliance with the protocol or adherence to therapy.
22. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
23. Treated with antibiotics for infection within one week prior to study entry.
24. Fever (> 38.1℃)
25. Have diastolic blood pressure of > 90 mm Hg resting at baseline despite medication. (Acceptable if on hypertensive medication and diastolic blood pressure is < 90 mm Hg.).
26. Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.
27. Enrollment in a concomitant clinical study