Summary

for people ages up to 21 years (full criteria)
at San Francisco, California and other locations
study started
estimated completion:
Sabine Mueller

Description

Summary

This research study involves an investigational product: Ad-RTS-hIL-12 given with veledimex for production of human IL-12. IL-12 is a protein that can improve the body's natural response to disease by enhancing the ability of the immune system to kill tumor cells and may interfere with blood flow to the tumor. The main purpose of this study is to evaluate the safety and tolerability of a single tumor injection of Ad-RTS-hIL-12 given with oral veledimex in the pediatric population.

Official Title

A Phase I Study of Ad-RTS-hIL-12, an Inducible Adenoviral Vector Engineered to Express hIL-12 in the Presence of the Activator Ligand Veledimex in Pediatric Brain Tumor Subjects

Details

Eligible patients will be stratified to one of two arms, according to clinical indication for tumor resection. Pediatric patients who are scheduled for craniotomy and tumor resection will receive one dose of veledimex before the resection procedure. Ad-RTS-hIL-12 will be administered by free-hand injection. Patients will continue on oral veledimex for 14 days.

Pediatric patients with diffuse intrinsic pontine glioma (DIPG) will receive Ad-RTS-hIL-12 by stereotactic injection and then will continue on oral veledimex for 14 days.

The study is divided into three periods: the screening period, the treatment period and the follow-up period.

Keywords

Pediatric Brain Tumor Diffuse Intrinsic Pontine Glioma DIPG Glioblastoma Anaplastic Astrocytoma High Grade Glioma (HGG) Not Otherwise Specified (NOS) Supratentorial Tumor NOS Glioma Brain Neoplasms Ad-RTS-hIL-12 oral veledimex Ad-RTS-hIL-12 +veledimex

Eligibility

You can join if…

Open to people ages up to 21 years

  1. Male or female subjects ≤ 21 years-of-age with the demonstrated ability to swallow capsules whole and who are willing to provide access to previously obtained biopsy results
  2. Provision of written informed consent and assent, when applicable, for tumor resection, stereotactic surgery, tumor biopsy, sample collection, and/or treatment with study drug prior to undergoing any study-specific procedures
  3. Arm 1: Evidence of recurrent or progressive supratentorial tumor, which has shown a >25% increase in bi dimensional measurements by MRI or is refractory with significant neuro deterioration that is not otherwise explained with no known curative therapy.

Arm 2: Clinical presentation of DIPG and compatible MRI with approximately 2/3 of the pons included. Subject should be ≥ 2 weeks and ≤ 10 weeks post standard focal radiotherapy (ie, dose of 5400 to 5960 cGy and maximum dexamethasone of 1 mg/m2/day)

  1. At the time of registration, subjects must have recovered from the toxic effects of previous treatments, as determined by the treating physician.
  2. Targeted agents, including small-molecular tyrosine kinase inhibitors: 2 weeks
  3. Other cytotoxic agents: 3 weeks
  4. Nitrosoureas: 6 weeks
  5. Monoclonal antibody immunotherapies (eg, PD-1, CTLA-4): 6 weeks
  6. Vaccine-based and/or viral therapy: 3 months
  7. On a stable or decreasing dose of dexamethasone for the previous 7 days
  8. Able to undergo standard MRI scans with contrast agent before enrollment and after treatment
  9. Have age-appropriate functional performance:
  10. Lansky score ≥ 50 or
  11. Karnofsky score > 50 or
  12. Eastern Cooperative Oncology Group (ECOG) score ≤ 2
  13. Have adequate bone marrow reserves and liver and kidney function, as assessed by the following laboratory requirements:
  14. Hemoglobin ≥ 8 g/L
  15. Absolute lymphocyte count ≥ 500/mm3
  16. Absolute neutrophil count ≥ 1000/mm3
  17. Platelets ≥ 100,000/mm3 (untransfused [> 5 days] without growth factors)
  18. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for age
  19. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for age
  20. Total bilirubin < 1.5 x ULN for age
  21. International normalized ratio (INR) and activated thromboplastin time within normal institutional limits
  22. Male and female subjects of childbearing potential must agree to use a highly reliable method of birth control (expected failure rate < 1% per year) from the Screening Visit through 28 days after the last dose of study drug. Women of childbearing potential must have a negative pregnancy test at screening.

You CAN'T join if...

  1. Radiotherapy treatment prior to the first veledimex dose:
  2. Focal radiation ≤ 4 weeks
  3. Whole-brain radiation ≤ 6 weeks
  4. Cranio-spinal radiation ≤ 12 weeks NOTE: Subjects in Arm 2 (ie, with DIPG) must be ≥ 2 weeks and ≤ 10 weeks after standard focal radiotherapy (dose of 5400 to 5960 cGy and maximum dexamethasone of 1 mg/m2/day)
  5. Subjects with clinically significant increased intracranial pressure (eg, impending herniation or requirement for immediate palliative treatment) or uncontrolled seizures
  6. Subjects whose body surface area (BSA) would expose them to < 75% or > 125% of the target dose
  7. Known immunosuppressive disease, autoimmune condition, and/or chronic viral infection(eg, human immunodeficiency virus [HIV], hepatitis)
  8. Use of systemic antibacterial, antifungal, or antiviral medications for the treatment of acute clinically significant infection within 2 weeks of first veledimex dose.Concomitant therapy for chronic infections is not allowed. Subjects must be afebrile prior to Ad-RTS-hIL-12 injection; only prophylactic antibiotic use is allowed perioperatively
  9. Use of enzyme-inducing antiepileptic drugs (EIAEDs) within 7 days prior to the first dose of study drug
  10. Other concurrent clinically active malignant disease, requiring treatment
  11. Nursing or pregnant females
  12. Prior exposure to veledimex
  13. . Use of medications that induce, inhibit, or are substrates of cytochrome p450 (CYP450)3A4 within 7 days prior to veledimex
  14. . Use of heparin or acetylsalicylic acid (ASA)
  15. . Presence of any contraindication for a neurosurgical procedure
  16. . Unstable or clinically significant concurrent medical condition

Locations

  • University of California San Francisco, Benioff Children's Hospital accepting new patients
    San Francisco California 94158 United States
  • Lurie Children's Hospital of Chicago accepting new patients
    Chicago Illinois 60611 United States
  • Dana- Farber Cancer Institute accepting new patients
    Boston Massachusetts 02215 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Ziopharm
ID
NCT03330197
Phase
Phase 1
Lead Scientist
Sabine Mueller
Study Type
Interventional
Last Updated
June 25, 2018