RECURRENT GLIOBLASTOMAPhase 2NCT02340156
Phase II Study of Combined Temozolomide and SGT-53 for Treatment of Recurrent Glioblastoma
A Phase 2 study testing SGT-53 and Temozolomide in people with RECURRENT GLIOBLASTOMA, run by SynerGene Therapeutics, Inc. at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- RECURRENT GLIOBLASTOMA
- What is being tested?
- SGT-53 and Temozolomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Dec 2014to Nov 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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
Who cannot join
- 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.
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- 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)
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Phase II Study of Combined Temozolomide and Targeted P53 Gene Therapy (SGT-53) for Treatment of Patients With Recurrent Glioblastoma
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..
Read the detailed description
The p53 is a vital human tumor suppressor gene. Loss of p53 suppressor function is present in the majority of human cancers. The p53 protein has a diverse range of functions including regulation of cell cycle checkpoints, cell death (apoptosis), senescence, DNA repair, maintenance of genomic integrity, and control of angiogenesis. Abnormalities of the p53 gene may impact the efficacy of standard anticancer treatments such as radiation and chemotherapy. P53 mutation and pathway dysfunction are associated with poor clinical outcomes and the presence of the p53 mutation correlates with resistance to chemotherapy and radiation. The development of somatic gene therapy has created the potential to restore wild type function of p53. SGT-53 is a complex of cationic liposome encapsulating a normal human wild type p53 DNA sequence in a plasmid backbone. This complex has been shown to efficiently and specifically deliver the p53 cDNA to the tumor cells and to cross the blood-brain barrier. Introduction of the p53 cDNA sequence is expected to restore wtp53 function in the apoptotic pathway. P53 restoration has been shown most effective in enhancing cytotoxicity in combination with an agent which results in DNA damage or initiates apoptosis. The primary mechanism of resistance to current standard chemotherapeutic agent Temozolomide (TMZ) is overexpression of O6-methylguanine-DNA-methyl transferase (MGMT), which repairs the TMZ-induced DNA lesion by removing the o6-guanine adducts. Thus, a means to down modulate MGMT activity would enhance the therapeutic effect of TMZ. A number of reports have indicated that increasing wtp53 expression can down-regulate expression of DNA repair genes such as MGMT and increases the sensitivity of tumor cells to alkylating agents. This is a Phase II clinical trial of the tumor-targeted SGT-53 nanocomplex in combination with chemotherapeutic agent, temozolomide which is the standard of care for Glioblastoma Multiforme (GBM) brain tumors. We propose to test the combination of SGT-53 and standard temozolomide to determine efficacy and safety in patients with confirmed glioblastoma who have proven tumor recurrence or progression.
- Conditions
- RECURRENT GLIOBLASTOMA
- Being tested
- SGT-53, Temozolomide
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SGT-53Genetic
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.
TemozolomideDrug
Also called Temodar
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Genetic: SGT-53; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor Response
The 6 month progression-free survival (PFS) was evaluated using RANO Response Criteria.
Measured: 6 months
Secondary outcomes (6)
Incidence of Treatment-Emergent Adverse Events
The safety of the combination of SGT-53 and Temozolomide was assessed by analysis of adverse experiences, clinical laboratory tests and physical examinations.
Measured: 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)
Progression-free survival is defined as the time from the date of enrollment to the date of disease progression, or death (any cause) on or prior to the clinical cutoff date, whichever occurs earlier. Subjects who do not have disease progression or have not died will be censored at the date of the last tumor assessment on or prior to the clinical cutoff.
Measured: 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)
Overall survival is defined as the time from the date of enrollment to the date of death from all causes.
Measured: From date of registration until the date of death from any cause, assessed up to 180 months.
Anti-tumor Activity
The anti-tumor activity of the combination of SGT-53 and Temozolomide was determined based upon the RANO criteria.
Measured: 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
Flow cytometry or histological examination was used to determine the level of apoptosis induced by SGT-53 in tumors resected 3 days after the first SGT-53 infusion (optional procedure)
Measured: 3 days
Nanoparticle Tumor Delivery
As an indicator of nanoparticle delivery to the tumors, DNA PCR was used to determine the presence of SGT-53 delivered exogenous wt p53 in the tumors. This analysis will be performed on any tumors resected 3 days after the first SGT-53 infusion (optional procedure)
Measured: 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2015 (estimated)
- Study startDec 2014
- Primary completionNov 2018
- Study completionNov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for RECURRENT GLIOBLASTOMAStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- SynerGene Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- John deGroot, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02340156
- Sponsor's protocol ID
- SGT53-02-2
- Status last verified
- Feb 2021
- First submitted
- 18 Dec 2014
- Last updated
- 3 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Combined Temozolomide and Targeted P53 Gene Therapy (SGT-53) for Treatment of Patients With Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT02340156
- Acronym / sponsor ID
- SGT53-02-2
- Conditions
- RECURRENT GLIOBLASTOMA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 1 participants (actual)
- Lead sponsor
- SynerGene Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- Dec 2014
- Primary completion
- Nov 2018 (actual)
- Study completion
- Nov 2018 (actual)
- First posted
- 16 Jan 2015 (estimated)
- Results
- Posted 3 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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..
Detailed description
The p53 is a vital human tumor suppressor gene. Loss of p53 suppressor function is present in the majority of human cancers. The p53 protein has a diverse range of functions including regulation of cell cycle checkpoints, cell death (apoptosis), senescence, DNA repair, maintenance of genomic integrity, and control of angiogenesis. Abnormalities of the p53 gene may impact the efficacy of standard anticancer treatments such as radiation and chemotherapy. P53 mutation and pathway dysfunction are associated with poor clinical outcomes and the presence of the p53 mutation correlates with resistance to chemotherapy and radiation. The development of somatic gene therapy has created the potential to restore wild type function of p53. SGT-53 is a complex of cationic liposome encapsulating a normal human wild type p53 DNA sequence in a plasmid backbone. This complex has been shown to efficiently and specifically deliver the p53 cDNA to the tumor cells and to cross the blood-brain barrier. Introduction of the p53 cDNA sequence is expected to restore wtp53 function in the apoptotic pathway. P53 restoration has been shown most effective in enhancing cytotoxicity in combination with an agent which results in DNA damage or initiates apoptosis. The primary mechanism of resistance to current standard chemotherapeutic agent Temozolomide (TMZ) is overexpression of O6-methylguanine-DNA-methyl transferase (MGMT), which repairs the TMZ-induced DNA lesion by removing the o6-guanine adducts. Thus, a means to down modulate MGMT activity would enhance the therapeutic effect of TMZ. A number of reports have indicated that increasing wtp53 expression can down-regulate expression of DNA repair genes such as MGMT and increases the sensitivity of tumor cells to alkylating agents. This is a Phase II clinical trial of the tumor-targeted SGT-53 nanocomplex in combination with chemotherapeutic agent, temozolomide which is the standard of care for Glioblastoma Multiforme (GBM) brain tumors. We propose to test the combination of SGT-53 and standard temozolomide to determine efficacy and safety in patients with confirmed glioblastoma who have proven tumor recurrence or progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SGT-53 with Temozolomide | Experimental | Genetic: SGT-53, Drug: TemozolomideSGT-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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- 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:
Key exclusion criteria (29 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SGT-53SGT-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. | Genetic | SGT-53 with Temozolomide |
| TemozolomideAlso: TemodarTMZ 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. | Drug | SGT-53 with Temozolomide |
Primary outcome
Tumor Response
Time frame: 6 months
The 6 month progression-free survival (PFS) was evaluated using RANO Response Criteria.
6 secondary outcomes
Incidence of Treatment-Emergent Adverse Events
Time frame: 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)
Time frame: 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)
Time frame: From date of registration until the date of death from any cause, assessed up to 180 months.
Anti-tumor Activity
Time frame: 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
Time frame: 3 days
Nanoparticle Tumor Delivery
Time frame: 3 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John deGroot, MD principal investigator
M.D. Anderson Cancer Center
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SGT-53 and Temozolomide in people with RECURRENT GLIOBLASTOMA, run by SynerGene Therapeutics, Inc. at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tumor Response (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2021.