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A Study of Ad-RTS-hIL-12 + Veledimex in Pediatric Subjects With Brain Tumors Including DIPG

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages N/A - 21 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

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, not in direct continuity with the ventricular system (e.g., there is physical separation between the tumor and ventricle, the tumor does not open directly into the ventricular system). Arm 2: Clinical presentation of DIPG and compatible MRI with approximately 2/3 of the pons included and without evidence of dissemination. Subjects 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) 4. At the time of registration, subjects must have recovered from the toxic effects of previous treatments, as determined by the treating physician. 1. Targeted agents, including small-molecular tyrosine kinase inhibitors: 2 weeks. 2. Other cytotoxic agents: 3 weeks. 3. Nitrosoureas: 6 weeks. 4. Monoclonal antibody immunotherapies (eg, PD-1, CTLA-4): 6 weeks. 5. Vaccine-based and/or viral therapy: 3 months. 5. On a stable or decreasing dose of dexamethasone for the previous 7 days. 6. Able to undergo standard MRI scans with contrast agent before enrollment and after treatment. 7. Have age-appropriate functional performance: 1. Lansky score ≥ 40 or. 2. Karnofsky score > 50 or. 3. Eastern Cooperative Oncology Group (ECOG) score ≤ 2. 8. Have adequate bone marrow reserves and liver and kidney function, as assessed by the following laboratory requirements: 1. Hemoglobin ≥ 8 g/L. 2. Absolute lymphocyte count ≥ 500/mm3. 3. Absolute neutrophil count ≥ 1000/mm3. 4. Platelets ≥ 100,000/mm3 (untransfused [> 5 days] without growth factors) 5. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for age. 6. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for age. 7. Total bilirubin < 1.5 x ULN for age. 8. International normalized ratio (INR) and activated thromboplastin time within normal institutional limits. 9. 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.

Exclusion Criteria:

1. Radiotherapy treatment prior to the first veledimex dose: 1. Focal radiation ≤ 4 weeks. 2. Whole-brain radiation ≤ 6 weeks. 3. 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) 2. Subjects with clinically significant increased intracranial pressure (eg, impending herniation or requirement for immediate palliative treatment) or uncontrolled seizures. 3. Subjects whose body surface area (BSA) would expose them to < 75% or > 125% of the target dose. 4. Known immunosuppressive disease, autoimmune condition, and/or chronic viral infection (eg, human immunodeficiency virus [HIV], hepatitis) 5. 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. 6. Use of enzyme-inducing antiepileptic drugs (EIAEDs) within 7 days prior to the first dose of study drug. 7. Other concurrent clinically active malignant disease, requiring treatment. 8. Nursing or pregnant females. 9. Prior exposure to veledimex. 10. Use of medications that induce, inhibit, or are substrates of cytochrome p450 (CYP450) 3A4 within 7 days prior to veledimex. 11. Use of heparin or acetylsalicylic acid (ASA). The use of systemic heparinization, or any ASA containing medications, is prohibited during active dosing with veledimex. Prophylactic heparin SC, per institutional protocol, or heparin when used for maintaining patency of an access port of a PICC line is permitted. 12. Presence of any contraindication for a neurosurgical procedure. 13. Unstable or clinically significant concurrent medical condition that would jeopardize the safety of a subject and/or their compliance with the protocol

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03330197
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Ziopharm
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Jill Buck
Principal Investigator Affiliation ZIOPHARM Oncology, Inc.
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Pediatric Brain Tumor, Diffuse Intrinsic Pontine Glioma
Additional 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. This arm has been completed and is currently closed to enrollment. 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.

Arms & Interventions

Arms

Experimental: Arm 1 - Closed

Intratumoral Ad-RTS-hIL-12 freehand injection after tumor resection and oral veledimex (activator ligand) in pediatric patients with brain tumors.

Experimental: Arm 2 - Open

Intratumoral Ad-RTS-hIL-12 stereotactic injection and oral veledimex (activator ligand) in pediatric patients with DIPG.

Interventions

Biological: - Ad-RTS-hIL-12

2.0 x 10^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12

Drug: - Oral Veledimex - Arm 1 (Pediatric Brain Tumor)

1 dose level (10mg/day) 15 oral daily doses of veledimex

Drug: - Oral Veledimex - Arm 2 (DIPG)

2 dose levels (10mg/day, 20mg/day) 14 oral daily doses of veledimex

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

San Francisco, California

Status

Recruiting

Address

University of California San Francisco, Benioff Children's Hospital

San Francisco, California, 94158

Site Contact

Melissa Clendenny

melissa.clendenny@ucsf.edu

415-476-0660

Lurie Children's Hospital of Chicago, Chicago, Illinois

Status

Recruiting

Address

Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611

Site Contact

Debra Tice

dtice@luriechildrens.org

312-227-4090

Dana- Farber Cancer Institute, Boston, Massachusetts

Status

Recruiting

Address

Dana- Farber Cancer Institute

Boston, Massachusetts, 02215

Site Contact

Elise Tierney

Elise_Tierney@dfci.harvard.edu

617-632-4386