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

• Status: Terminated
• Trial end date: 2018-11-01
• Target enrollment: 0
• Participant gender: All

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..

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: SynerGene Therapeutics, Inc.
• Treatments: Dacarbazine; Temozolomide

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)