Clinical Trials /

SGT-53 in Children With Recurrent or Progressive CNS Malignancies

NCT03554707

Description:

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

Related Conditions:
  • Malignant Central Nervous System Neoplasm
Recruiting Status:

Not yet recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: SGT-53 in Children With Recurrent or Progressive CNS Malignancies
  • Official Title: A Pilot Study of SGT-53 in Conjunction With Irradiation and Chemotherapy in Children With Recurrent or Progressive CNS Malignancies

Clinical Trial IDs

  • ORG STUDY ID: SGT53-00-1
  • NCT ID: NCT03554707

Conditions

  • Childhood CNS Tumor

Interventions

DrugSynonymsArms
IrinotecanCamptosar, OnivydeSGT-53 with radiation or drugs
TemozolomideTemodarSGT-53 with radiation or drugs
BevacizumabAvastinSGT-53 with radiation or drugs

Purpose

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

Detailed Description

      This clinical trial is a early phase 1, open label, single center, single arm study of the
      combination of intravenously administered SGT-53 and irradiation and/or chemotherapy in
      pediatric patients with recurrent or progressive CNS malignancies. The objective of the study
      is to establish the safety and feasibility of administration of SGT-53 in conjunction with
      conventional radiotherapy and/or chemotherapy in children with recurrent or refractory CNS
      malignancies.
    

Trial Arms

NameTypeDescriptionInterventions
SGT-53 with radiation or drugsExperimentalRadiation 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.
  • Irinotecan
  • Temozolomide
  • Bevacizumab

Eligibility Criteria

        Inclusion Criteria:

          -  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.

          -  Patients must have normal organ and marrow function.

          -  All patients of childbearing or child fathering potential must be willing to use an
             acceptable form of birth control while being treated on this study.

          -  Female patients must not be pregnant or nursing. Female patients must also have a
             negative serum pregnancy test at the time of enrollment.

          -  Patient and/or guardian have the ability to understand and the willingness to sign a
             written informed consent document according to institutional guidelines.

        Exclusion Criteria:

          -  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.
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Adverse Events
Time Frame:up to 13 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Response Rate
Time Frame:36 months
Safety Issue:
Description:The response rate will be calculated from the percentage of patients whose cancer shrinks or disappears after treatment.
Measure:Duration of Response
Time Frame:36 months
Safety Issue:
Description:The duration of response will be the time calculated from documentation of tumor response as indicated by response criteria, to disease progression.
Measure:Overall Survival
Time Frame:36 months
Safety Issue:
Description:Overall survival will be calculated from date of original diagnoses to death and also from the date of study registration to death.
Measure:Progressive-Free Survival (PFS)
Time Frame:36 months
Safety Issue:
Description:PFS will be calculated at all times during follow-up, with particular interest in the 6-month time point. Progression free survival will be calculated from date of first treatment to the date of first observation of progressive disease, non-reversible neurological progression or increasing steroid requirements (applies to stable disease only), death due to any cause, or early discontinuation of treatment.
Measure:Characterization of Phenotype of Patients
Time Frame:4-5 days
Safety Issue:
Description:Tissue will be obtained from each enrolling patient for subsequent testing for TP53 pathway functionality, including assessment of mdm2, p21, and other mutation or expression alterations. This analysis will also include measures of commonly assessed polymorphisms, including MGMT methylation assessment, ATRX mutation among others.
Measure:Feasibility of Droplet PCR Assays to Monitor for Tumor Burden
Time Frame:12 months
Safety Issue:
Description:Droplet PCR will be used to assess for the presence of circulating tumor DNA

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:SynerGene Therapeutics, Inc.

Trial Keywords

  • Childhood CNS tumor
  • Recurrent CNS malignancies
  • Progressive CNS malignancies
  • Refractory CNS malignancies

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