SGT-53 in Children With Recurrent or Progressive CNS Malignancies

NCT03554707 | Unknown Early Phase 1 FDA Drug

• 1 other identifier: SGT53-00-1
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

An early phase 1 for pediatric patients with recurrent or progressive CNS malignancies

Conditions

Childhood CNS Tumor

Keywords

Childhood CNS tumor; Recurrent CNS malignancies; Progressive CNS malignancies; Refractory CNS malignancies

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events

  An adverse event (AE) was any untoward medical occurrence that began or worsened in grade after the start of study drug through 30 days after the last dose. The safety will be assessed by the number and severity of any AE or serious adverse events (SAE) experienced by the patients, and by their relationship to the study drug SGT-53 (e.g. definitely, probably, possibly, unlikely or unrelated). Severity will be graded according to NCI CTCAE version 4.0.

  up to 13 months

Secondary Outcomes (6)

• Response Rate

  36 months

• Duration of Response

  36 months

• Overall Survival

  36 months

• Progressive-Free Survival (PFS)

  36 months

• Characterization of Phenotype of Patients

  4-5 days

Study Arms (1)

SGT-53 with radiation or drugs

EXPERIMENTAL

Radiation phase: SGT-53 will be given at 2.1 mg DNA/m2 twice weekly for the first week of radiation therapy, and then increase to 2.8 mg DNA/m2 twice weekly. Radiation therapy will be administered as per clinical care, with a target of fifteen (15) fractions, but patients with other clinically-determined radiation plans will be allowed. Chemotherapy phase: SGT-53 will be administered at the highest tolerated dose given during radiation phase. Irinotecan will be given at a dose of 50mg/m2/dose IV daily for five days in a 4-week cycle. Temozolomide will be given at a dose of 100mg/m2 PO daily for five days in a 4-week cycle and bevacizumab will be given at a dose of 10mg/kg IV every two weeks in a 4-week cycle.

Genetic: SGT-53; Radiation: Radiation; Drug: Irinotecan; Drug: Temozolomide; Drug: Bevacizumab

Interventions

SGT-53 GENETIC

2.1 mg DNA/m2 or 2.8 mg DNA/m2 twice weekly

SGT-53 with radiation or drugs

Radiation RADIATION

Standard radiation plan

SGT-53 with radiation or drugs

Irinotecan DRUG

50mg/m2/dose IV daily for five days in a 4-week cycle

Also known as: Camptosar, Onivyde

SGT-53 with radiation or drugs

Temozolomide DRUG

100mg/m2 PO daily for five days in a 4-week cycle

Also known as: Temodar

SGT-53 with radiation or drugs

Bevacizumab DRUG

10mg/kg IV every two weeks in a 4-week cycle

Also known as: Avastin

SGT-53 with radiation or drugs

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must have a recurrent, progressive, or refractory CNS malignancy for which there are not known curative options. Low-grade glioma, craniopharyngioma, and other non-malignant CNS tumors are excluded.
• Tumor must be measureable, defined as a tumor that can be accurately measured in two perpendicular dimensions on MRI.
• Patients with metastatic disease are eligible but must have at least one target lesions which is measurable.
• Patients must have available archival (formalin-fixed paraffin embedded) or fresh tumor tissue for correlative studies.
• Patients must be \>1yrs and \<21 years of age.
• Must have recovered from all surgical interventions prior to the start of the Radiation and Chemotherapy Phases.
• Patients must have recovered from the acute effects of prior therapy.
• There is a maximum of 3 previous myelosuppressive therapy regimens. However, there is no maximum number of therapeutic courses.
• Patients must have received their last dose of known myelosuppressive therapy at least three (3) weeks prior to receipt of SGT-53.
• Patients must have received their last dose of biological agent \>7 days prior to receipt of SGT-53.
• Patients must be far enough from previous irradiation that in the opinion of a radiation oncologist using standard fractionation is deemed to be reasonable from a clinical standard of care perspective.
• Patients who are receiving dexamethasone or other corticosteroids must be on a stable or decreasing dose for at least one (1) week prior to enrollment.
• Patients must have received their last dose of any short acting growth factor at least one week prior to treatment, for long acting or pegylated growth factors, the last dose must be at least two (2) weeks prior to start of treatment.
• Patients with neurologic deficits must have deficits that have been stable in grade for a minimum of one week prior to enrollment.
• Performance status (Karnofsky PS for \>16yrs, or Lansky PS for \<16yrs) assessed within two weeks must be \>50.

You may not qualify if:

• Patients with any clinically significant unrelated systemic illness (serious infection or significant cardiac, pulmonary, hepatic, or other organ dysfunction) that is likely to interfere with ability to tolerate study therapy or study procedure results.
• Patients with low-grade gliomas, craniopharyngioma, or extracranial tumors with CNS metastases.
• Patients who are receiving any other investigational drug therapy.
• Patients who require therapeutic anti-coagulation.
• Patients who in the opinion of the investigator cannot adhere to protocol requirements.
• Patients with history of clinically significant clot or hemorrhage are eligible but will not receive bevacizumab during chemotherapy regimen.
• Unavailability of the chemotherapy due to insurance coverage or other logistical issues is an ineligibility criterion.
• Patients may not be on immunosuppressive therapy, including corticosteroids (with the exception of physiologic replacement, defined as 0.75mg/m2/day) at time of enrollment. However, patients who require intermittent use of bronchodilators or local steroid injections will not be excluded from the study.

Sponsors & Collaborators

• SynerGene Therapeutics, Inc.: lead

Study Sites (1)

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms

Interventions

Radiation; Irinotecan; irinotecan sucrosofate; Temozolomide; Bevacizumab

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Physical Phenomena; Camptothecin; Alkaloids; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Eugene Hwang, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sabrina Malik

CONTACT

202-476-5115; SaMalik@childrensnational.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2018
• First Posted: June 13, 2018
• Study Start: June 1, 2022
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2024
• Last Updated: February 8, 2022

Record last verified: 2022-02

Locations

US (1)