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

NCT02340156 | Terminated Phase 2 Results DMC

• 1 other identifier: SGT53-02-2
• Study Type: interventional
• Target: 1
• Locations: 2 countries
• Sites: 2

Brief 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..

Conditions

RECURRENT GLIOBLASTOMA

Outcome Measures

Primary Outcomes (1)

• Tumor Response

  The 6 month progression-free survival (PFS) was evaluated using RANO Response Criteria.

  6 months

Secondary Outcomes (6)

• Incidence of Treatment-Emergent Adverse Events

  Study drug initiation through 30 days after the last dose of study drug or EOS, whichever is later, approximately 90 days.

• Progression-free Survival (PFS)

  From date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months.

• Overall Survival (OS)

  From date of registration until the date of death from any cause, assessed up to 180 months.

• Anti-tumor Activity

  From date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months.

• Induction of Apoptosis

  3 days

Study Arms (1)

SGT-53 with Temozolomide

EXPERIMENTAL

SGT-53, at 3.6 mg DNA/infusion, will be administered twice weekly in a 28 day cycle starting on Day 1 (cycle 1), Day 29 (cycle 2) and Day 57 (cycle 3). Temozolomide (TMZ) will be administered by mouth daily on days 9-13 of each cycle. Patients who are responding to treatment may receive three additional cycles of SGT-53/TMZ therapy or continue on TMZ alone at investigator's discretion. Surgical resection of recurrent or progressive tumor for tumor analysis is an optional procedure. In these individuals SGT-53, at 3.6 mg DNA/infusion, will be administered twice (on days -1 and -3) in the week prior to surgery. Surgical resection is Day 0. 14-21 days post operatively and having recovered from the effects of surgery, the patients will then start cyclical TMZ with SGT-53 as described above.

Genetic: SGT-53; Drug: Temozolomide

Interventions

SGT-53 GENETIC

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.

SGT-53 with Temozolomide

Temozolomide DRUG

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.

Also known as: Temodar

SGT-53 with Temozolomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• weeks from cytotoxic agents
• weeks from nitrosoureas
• weeks from any investigational agent
• week from non-cytotoxic agents
• weeks from radiotherapy
• Karnofsky performance status ≥ 60%.

You may not qualify if:

• 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

Sponsors & Collaborators

• SynerGene Therapeutics, Inc.: lead

Study Sites (2)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

The number of participant was too small for statistical analysis. The study was terminated.

Results Point of Contact

• Title: Senior Consultant
• Organization: SynerGene Therapeutics, Inc.

clinicaltrial@synergeneus.com

301-706-1509

Study Officials

• John deGroot, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2014
• First Posted: January 16, 2015
• Study Start: December 1, 2014
• Primary Completion: November 1, 2018
• Study Completion: November 1, 2018
• Last Updated: March 3, 2021
• Results First Posted: March 3, 2021

Record last verified: 2021-02

Locations

US (1); TW (1)