Phase II Study of Combined Temozolomide and SGT-53 for Treatment of Recurrent Glioblastoma
Condition: RECURRENT GLIOBLASTOMA
MeSH terms: Glioblastoma; Recurrence
Intervention: SGT-53; Temozolomide
Intervention description: SGT-53, at 3.6 mg DNA per infusion, will be administered twice per week for 3 weeks (on Day 1, 4, 8, 11, 15 and 18 of each cycle) for 3 cycles. If SGT-53-related toxicity occurs, the dose of SGT-53 will be de-escalated to 2.4 or 1.2 mg DNA/infusion when appropriate.; TMZ will be administered orally on days 9-13 of each cycle. In cycle 1, the dose of TMZ will be 150 mg/m². If the TMZ-related toxicities are tolerated in cycle 1, the dose of TMZ will be escalated to 200 mg/m² for cycle 2 and beyond. If TMZ-related toxicity occurs, the dose if TMZ will be de-escalated to 125 mg/m² (dose level -1), 100 mg/m² (dose level -2) or 75 mg/m² (dose level -3) when appropriate.
Intervention MeSH terms: Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This Phase II clinical trial is an open label, single arm, multicenter study of the
      combination of intravenously administered SGT-53 and oral temozolomide in patients with
      confirmed glioblastoma who have proven tumor recurrence or progression. The objective of this
      trial is to assess 6 month progression free survival (PFS), overall survival (OS), anti-tumor
      activity, safety and possibly to evaluate, nanoparticle delivery to tumor site, and the
      induction of apoptosis in the tumor..
    

Eligibility criteria:

        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)