A Study of SGT-53 in Children With Refractory or Recurrent Solid Tumors

NCT02354547 | Suspended Phase 1 DMC

• 1 other identifier: SGT53-01-2
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Neoplasm

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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.)

  3-18 weeks

• Anti-tumor activity (evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.)

  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)

  3-18 weeks

Study Arms (1)

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.

Genetic: SGT-53; Drug: Topotecan; Drug: Cyclophosphamide

Interventions

SGT-53 GENETIC

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.

SGT-53 with Topotecan/Cyclophosphamide

Topotecan DRUG

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.

Also known as: Hycamtin

SGT-53 with Topotecan/Cyclophosphamide

Cyclophosphamide DRUG

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.

Also known as: Cytoxan®, Neosar®

SGT-53 with Topotecan/Cyclophosphamide

Eligibility Criteria

• Age: 12 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• SynerGene Therapeutics, Inc.: lead

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Topotecan; Cyclophosphamide

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Jodi Muscal, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• 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: February 3, 2015
• Study Start: December 1, 2014
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 30, 2025

Record last verified: 2025-05

Locations

US (1)