NeoplasmPhase 1NCT02354547
A Study of SGT-53 in Children With Refractory or Recurrent Solid Tumors
A Phase 1 study testing SGT-53, Topotecan and Cyclophosphamide in people with Neoplasm, run by SynerGene Therapeutics, Inc. at 1 site in United States.
Trial summary
The purpose of this study is to determine the dose limiting toxicities and recommended phase 2 dose of SGT-53 alone and in combination with topotecan and cyclophosphamide in pediatric patients with recurrent or refractory solid tumors. Read more about this study
- Who is it for?
- Ages 12 months to 21 years
- Conditions the study is for
- Neoplasm
- What is being tested?
- SGT-53, Topotecan and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2014to Dec 2027
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 12 months to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- All patients and/or their parents or legally authorized representatives must sign a written informed consent.
- Patients must be > than 12 months and ≤ 21 years of age at the time of study enrollment.
- Body surface Area (For Dose Level -1): Patients must be ≥ 0.38 m² at the time of study enrollment.
- Patients with relapsed or refractory solid tumors (excluding primary central nervous system tumors) are eligible. Patients must have had histologic verification of malignancy at original diagnosis or relapse.
- Patients must have either measurable or evaluable disease.
- Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
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- Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age.
- Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy:
- At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea).
- At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor.
- At least 7 days after the last dose of a biologic agent.
- At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines.
- At least 3 half-lives of the antibody after the last dose of a monoclonal antibody.
- At least 14 days after local palliative XRT (small port); At least 150 days must have elapsed if prior TBI, craniospinal XRT or if ≥ 50% radiation of pelvis; At least 42 days must have elapsed if other substantial bone marrow radiation.
- No evidence of active graft vs. host disease and at least 84 days must have elapsed after transplant or stem cell infusion.
- Patient must not have had prior exposure to gene vector delivery products within 3 months.
- Patients may not have had prior SGT-53. Patient who have received prior topotecan, cyclophosphamide, or both are eligible.
- Adequate Bone Marrow Function:
- Peripheral absolute neutrophil count (ANC) ≥ 1000/mm³.
- Platelet count ≥ 100,000/mm³.
- Adequate Renal Function:
- Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m² OR age/gender appropriate serum creatinine.
- Adequate Liver Function:
- Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age.
- SGPT (ALT) ≤ 110 U/L.
- Serum albumin ≥ 2 g/dL.
Who cannot join
- Are pregnant or breast-feeding women.
- Concomitant medications:
- Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible.
- Patients who are currently receiving another investigational drug are not eligible.
- Patients who are currently receiving other anti-cancer agents are not eligible.
- Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
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- Patients who have an uncontrolled infection are not eligible.
- Patients who have received a solid organ transplantation are not eligible.
- Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Study of SGT-53, a TfRscFv-Liposome-p53 Complex, in Children With Refractory or Recurrent Solid Tumors
The purpose of this study is to determine the dose limiting toxicities and recommended phase 2 dose of SGT-53 alone and in combination with topotecan and cyclophosphamide in pediatric patients with recurrent or refractory solid tumors.
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. 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. Though mutated p53 is uncommon in childhood cancer, children with adrenocortical tumor and rhabdomyosarcoma have been found to have p53 mutations. Additionally, wild type p53 may be suppressed in tumors through pathway crosstalk. For example, in sarcomas, a common childhood solid tumor, activation of MDM2 effectively inactivates p53. Thus, the treatment proposed in this trial to reintroduce p53 may offer benefit even in patients with p53 wild-type tumors. Moreover, the SGT-53 treatment can significantly sensitize pediatric cancer cell lines to the killing effect of the standard chemotherapeutic agents, topotecan and cyclophosphamide. Thus, we propose to assess the efficacy of this combination therapy in pediatric patients with refractory or recurrent solid tumors. This phase I clinical trial is to determine the dose limiting toxicities (DLT), recommended phase 2 dose, and maximum tolerated dose (MTD) of SGT-53 (if reached) alone and in combination with conventional chemotherapy in pediatric patients with recurrent or refractory solid tumors. In addition, pharmacokinetics of escalating doses of SGT-53 is studied.
- Conditions
- Neoplasm
- Being tested
- SGT-53, Topotecan, Cyclophosphamide
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SGT-53Genetic
The starting dose of SGT-53 will be 1.4 mg DNA/m² (dose level 1). If MTD is reached at dose level 1, subsequent cohort will be treated at 0.7 mg DNA/m² (dose level -1). If MTD is not reached at 2.1 mg DNA/m² (dose level 2), additional dose level(s) may be added. Intra-patient escalation is not allowed. Topotecan/cyclophosphamide will not be administered in cycle 1. In cycle 2, SGT-53 will be administered in combination with 0.6 mg/m² topotecan and 200 mg/m² cyclophosphamide IV daily for 5 days. Beginning in cycle 3, if no DLTs in cycle 2, topotecan and cyclophosphamide will be escalated to 0.75 mg/m² and 250 mg/m², respectively. No further dose escalation is permitted. If DLT develops at the higher doses, the doses should be decreased back to those in cycle 2.
TopotecanDrug
Also called Hycamtin
Topotecan/cyclophosphamide will not be administered in cycle 1. In cycle 2, 0.6 mg/m² topotecan will be administered in combination with SGT-53 and cyclophosphamide IV daily for 5 days. Beginning in cycle 3, if no DLTs in cycle 2, topotecan will be escalated to 0.75 mg/m². No further dose escalation is permitted. If DLT develops at the higher doses, the dose should be decreased back to those in cycle 2.
CyclophosphamideDrug
Also called Cytoxan®, Neosar®
Topotecan/cyclophosphamide will not be administered in cycle 1. In cycle 2, 200 mg/m² cyclophosphamide will be administered in combination with topotecan and SGT-53 IV daily for 5 days. Beginning in cycle 3, if no DLTs in cycle 2, cyclophosphamide will be escalated to 250 mg/m². No further dose escalation is permitted. If DLT develops at the higher doses, the dose should be decreased back to those in cycle 2.
| Study group | Role | What they receive |
|---|---|---|
| SGT-53 with Topotecan/Cyclophosphamide | Experimental | There will be 4-6 cycles (21 days/cycle) of therapy in this trial. In cycle 1, SGT-53 will be given as a single agent twice weekly starting at 1.4 mg/m² of DNA per infusion to evaluate single-agent toxicity. Pharmacokinetic studies will be performed. In the absence of dose limiting toxicity, patients will proceed to cycle 2 even if they have progressive disease. Starting in cycle 2, SGT-53 will be administered twice-weekly in combination with topotecan and cyclophosphamide administered daily for 5 days, days 1-5 of each cycle. Day 1 of each combination cycle is the first day on which topotecan and cyclophosphamide are administered with SGT-53. If a subject has at least stable disease after four cycles of therapy and is tolerating protocol therapy, two additional cycles may be considered. Receives: Genetic: SGT-53; Drug: Topotecan; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicities (DLT)
The dose limiting toxicities of SGT-53 alone and in combination with topotecan and cyclophosphamide in pediatric patients with recurrent or refractory solid tumors will be assessed by any adverse events that are possibly, probably or definitely attributable to study drugs.
Measured: 3-18 weeks
Recommended phase 2 dose (RP2D)
The recommended phase 2 dose of SGT-53 alone and in combination with topotecan and cyclophosphamide in pediatric patients with recurrent or refractory solid tumors will be assessed.
Measured: 3-18 weeks
Secondary outcomes (3)
Tolerability of systemic intravenous infusion (assessed by any adverse events related to infusion of study drugs according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.)
Tolerability of systemic intravenous infusion of SGT-53 alone and in combination with topotecan and cyclophosphamide will be assessed by any adverse events related to infusion of study drugs according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Measured: 3-18 weeks
Anti-tumor activity (evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.)
Anti-tumor activity of SGT-53 alone and in combination with topotecan and cyclophosphamide will be evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.
Measured: 3-18 weeks
Concentration of SGT-53 over time will be characterized by Cmax and clearance (Pharmacokinetic will be performed to evaluate the concentration of SGT-53 in patient's blood over time)
Pharmacokinetic will be performed to evaluate the concentration of SGT-53 in patient's blood over time
Measured: 3-18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2015 (estimated)
- Study startDec 2014
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Why it stopped: slow recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeoplasmStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- SynerGene Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jodi Muscal, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02354547
- Sponsor's protocol ID
- SGT53-01-2
- Status last verified
- May 2026
- First submitted
- 18 Dec 2014
- Last updated
- 8 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of SGT-53, a TfRscFv-Liposome-p53 Complex, in Children With Refractory or Recurrent Solid Tumors
- ClinicalTrials.gov ID
- NCT02354547
- Acronym / sponsor ID
- SGT53-01-2
- Conditions
- Neoplasm
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: slow recruitment
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- SynerGene Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- Dec 2014
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 3 Feb 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the dose limiting toxicities and recommended phase 2 dose of SGT-53 alone and in combination with topotecan and cyclophosphamide in pediatric patients with recurrent or refractory solid tumors.
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. 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. Though mutated p53 is uncommon in childhood cancer, children with adrenocortical tumor and rhabdomyosarcoma have been found to have p53 mutations. Additionally, wild type p53 may be suppressed in tumors through pathway crosstalk. For example, in sarcomas, a common childhood solid tumor, activation of MDM2 effectively inactivates p53. Thus, the treatment proposed in this trial to reintroduce p53 may offer benefit even in patients with p53 wild-type tumors. Moreover, the SGT-53 treatment can significantly sensitize pediatric cancer cell lines to the killing effect of the standard chemotherapeutic agents, topotecan and cyclophosphamide. Thus, we propose to assess the efficacy of this combination therapy in pediatric patients with refractory or recurrent solid tumors. This phase I clinical trial is to determine the dose limiting toxicities (DLT), recommended phase 2 dose, and maximum tolerated dose (MTD) of SGT-53 (if reached) alone and in combination with conventional chemotherapy in pediatric patients with recurrent or refractory solid tumors. In addition, pharmacokinetics of escalating doses of SGT-53 is studied.
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 Topotecan/Cyclophosphamide | Experimental | Genetic: SGT-53, Drug: Topotecan, Drug: CyclophosphamideThere will be 4-6 cycles (21 days/cycle) of therapy in this trial. In cycle 1, SGT-53 will be given as a single agent twice weekly starting at 1.4 mg/m² of DNA per infusion to evaluate single-agent toxicity. Pharmacokinetic studies will be performed. In the absence of dose limiting toxicity, patients will proceed to cycle 2 even if they have progressive disease. Starting in cycle 2, SGT-53 will be administered twice-weekly in combination with topotecan and cyclophosphamide administered daily for 5 days, days 1-5 of each cycle. Day 1 of each combination cycle is the first day on which topotecan and cyclophosphamide are administered with SGT-53. If a subject has at least stable disease after four cycles of therapy and is tolerating protocol therapy, two additional cycles may be considered. |
Who may qualify
- Ages
- 12 months to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (26 listed)
- All patients and/or their parents or legally authorized representatives must sign a written informed consent.
- Patients must be > than 12 months and ≤ 21 years of age at the time of study enrollment.
- Body surface Area (For Dose Level -1): Patients must be ≥ 0.38 m² at the time of study enrollment.
- Patients with relapsed or refractory solid tumors (excluding primary central nervous system tumors) are eligible. Patients must have had histologic verification of malignancy at original diagnosis or relapse.
- Patients must have either measurable or evaluable disease.
Key exclusion criteria (9 listed)
- Are pregnant or breast-feeding women.
- Concomitant medications:
- Patients who have an uncontrolled infection are not eligible.
- Patients who have received a solid organ transplantation are not eligible.
- Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
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-53The starting dose of SGT-53 will be 1.4 mg DNA/m² (dose level 1). If MTD is reached at dose level 1, subsequent cohort will be treated at 0.7 mg DNA/m² (dose level -1). If MTD is not reached at 2.1 mg DNA/m² (dose level 2), additional dose level(s) may be added. Intra-patient escalation is not allowed. Topotecan/cyclophosphamide will not be administered in cycle 1. In cycle 2, SGT-53 will be administered in combination with 0.6 mg/m² topotecan and 200 mg/m² cyclophosphamide IV daily for 5 days. Beginning in cycle 3, if no DLTs in cycle 2, topotecan and cyclophosphamide will be escalated to 0.75 mg/m² and 250 mg/m², respectively. No further dose escalation is permitted. If DLT develops at the higher doses, the doses should be decreased back to those in cycle 2. | Genetic | SGT-53 with Topotecan/Cyclophosphamide |
| TopotecanAlso: HycamtinTopotecan/cyclophosphamide will not be administered in cycle 1. In cycle 2, 0.6 mg/m² topotecan will be administered in combination with SGT-53 and cyclophosphamide IV daily for 5 days. Beginning in cycle 3, if no DLTs in cycle 2, topotecan will be escalated to 0.75 mg/m². No further dose escalation is permitted. If DLT develops at the higher doses, the dose should be decreased back to those in cycle 2. | Drug | SGT-53 with Topotecan/Cyclophosphamide |
| CyclophosphamideAlso: Cytoxan®, Neosar®Topotecan/cyclophosphamide will not be administered in cycle 1. In cycle 2, 200 mg/m² cyclophosphamide will be administered in combination with topotecan and SGT-53 IV daily for 5 days. Beginning in cycle 3, if no DLTs in cycle 2, cyclophosphamide will be escalated to 250 mg/m². No further dose escalation is permitted. If DLT develops at the higher doses, the dose should be decreased back to those in cycle 2. | Drug | SGT-53 with Topotecan/Cyclophosphamide |
Primary outcome
Dose limiting toxicities (DLT)
Time frame: 3-18 weeks
The dose limiting toxicities of SGT-53 alone and in combination with topotecan and cyclophosphamide in pediatric patients with recurrent or refractory solid tumors will be assessed by any adverse events that are possibly, probably or definitely attributable to study drugs.
Recommended phase 2 dose (RP2D)
Time frame: 3-18 weeks
The recommended phase 2 dose of SGT-53 alone and in combination with topotecan and cyclophosphamide in pediatric patients with recurrent or refractory solid tumors will be assessed.
3 secondary outcomes
Tolerability of systemic intravenous infusion (assessed by any adverse events related to infusion of study drugs according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.)
Time frame: 3-18 weeks
Anti-tumor activity (evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.)
Time frame: 3-18 weeks
Concentration of SGT-53 over time will be characterized by Cmax and clearance (Pharmacokinetic will be performed to evaluate the concentration of SGT-53 in patient's blood over time)
Time frame: 3-18 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2026.
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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.
Jodi Muscal, MD principal investigator
Baylor College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SGT-53, Topotecan and Cyclophosphamide in people with Neoplasm, run by SynerGene Therapeutics, Inc. at 1 site in United States.
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 26 inclusion and 9 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: paused, as of the sponsor's last update on 8 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Dose limiting toxicities (DLT) (time frame: 3-18 weeks). The study lists 2 primary outcomes in all. 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 8 May 2026.