NCT02354547

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

A Phase I Study of SGT-53, a TfRscFv-Liposome-p53 Complex, in Children With Refractory or Recurrent Solid Tumors

• Status: Suspended
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Sponsor: SynerGene Therapeutics, Inc. · Industry
• Sex: All
• Age: 12 Months – 21 Years
• Healthy volunteers: Not accepted

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.

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

Interventions

Type	Name	Description
GENETIC	SGT-53	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.
DRUG	Topotecan	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.
DRUG	Cyclophosphamide	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.

Timeline

• Start date: 2014-12-01
• Primary completion: 2025-12-01
• Completion: 2026-12-01
• First posted: 2015-02-03
• Last updated: 2025-05-30

Locations

1 site across 1 country: United States