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A Study of Ad-RTS-hIL-12 With Veledimex in Subjects With Glioblastoma or Malignant Glioma

This study is currently recruiting participants.
See Contacts and Locations
Verified February 2017 by Ziopharm
Sponsor:
Information provided by (Responsible Party):
Ziopharm
ClinicalTrials.gov Identifier:
NCT02026271
First received: December 16, 2013
Last updated: February 13, 2017
Last verified: February 2017
  Purpose

This research study involves two investigational drugs, veledimex, an activator ligand (INXN-1001) in combination with an Adenovirus Vector Engineered to Express hIL-12 (INXN-2001). IL-12 is a protein that may 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 INXN-2001 given in combination with oral veledimex.


Condition Intervention Phase
Glioblastoma Multiforme Anaplastic Oligoastrocytoma Biological: INXN-2001 Drug: veledimex Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
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 Subjects With Recurrent or Progressive Glioblastoma or Grade III Malignant Glioma

Resource links provided by NLM:


Further study details as provided by Ziopharm:

Primary Outcome Measures:
  • Safety and tolerability of varying doses of intratumoral Ad-RTS-hIL-12 and oral veledimex doses in subjects with recurrent or progressive glioblastoma or Grade III malignant glioma [ Time Frame: 3 years ]
    Evaluation will be based on the incidence, intensity, and type of Adverse Events (AEs). Clinically significant changes in the subjects' physical examinations, vital signs, and ECG evaluations, and clinical manifestations relevant to abnormal laboratory values will be captured as AEs.


Secondary Outcome Measures:
  • Veledimex maximum tolerated dose (MTD) when given with varying doses of intratumoral Ad-RTS-hIL-12 [ Time Frame: 3 years ]
  • Veledimex pharmacokinetic profile and veledimex concentration ratop betwee the brain tumor and the blood [ Time Frame: 3 years ]
    Veledimex PK parameters to be determined will include, but are not limited to, the maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), half-life (t1/2), area-under-the-concentration versus time curve (AUC), volume of distribution (Vd), and clearance (CL). Where possible, descriptive statistics of the PK parameters will be provided; individual subject veledimex concentrations, actual sampling times, and PK parameters will be listed.

  • Cellular and humoral immune responses elicited by Ad-RTS-hIL-12 and veledimex [ Time Frame: 3 years ]
  • Tumor Objective Response Rate (ORR) [ Time Frame: 3 years ]
  • Progression-free survival (PFS) [ Time Frame: 3 years ]
  • Overall survival (OS) [ Time Frame: 3 years ]

Estimated Enrollment: 48
Study Start Date: June 2015
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Veledimex in combination with INXN-2001
varying doses of intratumoral INXN-2001 (Ad-RTS-hIL-12) and oral veledimex (activator ligand).
Biological: INXN-2001
  • 2.0 x 10^11 viral particles (vp) per injection or 1.0 x 10^12 viral particles (vp) per injection
  • one intratumoral injection of INXN-2001
Other Name: Ad-RTS-hIL-12
Drug: veledimex
  • 4 doses (20mg/day, 40mg/day, 80mg/day, and 120mg/day)
  • 14 oral daily doses of INXN-1001
  • 1 Expansion cohort at a single dose level at or below MTD
Other Names:
  • INXN-1001
  • Activator Ligand

Detailed Description:

Eligible patients will be stratified to one of two groups, according to clinical indication for tumor resection. Patients who are scheduled for a standard of care 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.

Patients not scheduled for tumor resection 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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female subjects ≥ 18 and ≤ 75 years of age
  2. Provision of written informed consent for tumor resection, stereotactic surgery, tumor biopsy, samples collection and treatment with investigational products prior to undergoing any study procedures
  3. Histologically confirmed supratentorial glioblastoma or other WHO grade III or IV malignant glioma from archival tissue.
  4. Evidence of tumor recurrence/progression by MRI (RANO criteria) post standard initial therapy.
  5. Previous standard of care anti-tumor treatment including surgery and/or biopsy and chemoradiation. The washout periods from prior therapies are intended as follows:

    1. Nitrosoureas: 6 weeks
    2. Other cytotoxic agents: 4 weeks
    3. Anti-angiogenic agents including bevacizumab: 4 weeks
    4. Targeted agents including small-molecule tyrosine kinase inhibitors: 2 weeks
    5. Experimental immunotherapies: 3 months
    6. Vaccine based therapy: 3 months
  6. Able to undergo standard MRI scans with contrast agent
  7. Karnofsky Performance Status ≥ 70
  8. Adequate bone marrow reserves and liver and kidney function, as assessed by the following laboratory requirements:

    1. Hemoglobin ≥ 9 g/L
    2. Lymphocytes > 500/ mm3
    3. Absolute Neutrophil Count ≥ 1500/ mm3
    4. Platelets ≥ 100,000/ mm3
    5. Serum creatinine ≤ 1.5 x ULN
    6. AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN. For subjects with documented liver metastases, ALT and AST ≤ 5 × ULN
    7. Total bilirubin < 1.5 x ULN
    8. International Normalized Ratio (INR) and activated Partial Thromboplastin Time [PTT] within normal institutional limits
  9. Male and female subjects must agree to use a highly reliable method of birth control (expected failure rate less than 5% 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 within 4 weeks or less prior to starting first veledimex dose
  2. Subjects with clinically significant increased intracranial pressure or uncontrolled seizures.
  3. Known immunosuppressive disease, autoimmune conditions, and /or chronic viral infections
  4. Use of systemic antibacterials, antifungals or antivirals 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 permitted perioperatively.
  5. Use of enzyme-inducing anti-epileptic drugs (EIAED) within 7 days prior to the first dose of study drug.
  6. Other concurrent clinically active malignant disease, requiring treatment, with the exception of non-melanoma cancers of the skin or carcinoma in-situ of the cervix or non-metastatic prostate cancer.
  7. Nursing or pregnant females
  8. Prior exposure to veledimex
  9. Use of medications that induce, inhibit or are substrates of CYP450 3A4 within 7 days prior to the first veledimex dosing
  10. Presence of any contra-indication for a neurosurgical procedure
  11. Unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator or medical monitor, jeopardize the safety of a subject and/or their compliance with the protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02026271

Contacts
Contact: Cori Ann Jones cjones@ziopharm.com
Contact: Jill Buck jbuck@ziopharm.com

Locations
United States, California
Cedars-Sinai Recruiting
Los Angeles, California, United States, 90048
United States, Illinois
Northwestern Recruiting
Chicago, Illinois, United States, 60611
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
United States, Massachusetts
Brigham & Women's Recruiting
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Ziopharm
Investigators
Study Director: Francois Lebel, MD ZIOPHARM Oncology
  More Information

Responsible Party: Ziopharm
ClinicalTrials.gov Identifier: NCT02026271     History of Changes
Other Study ID Numbers: ATI001-102
Study First Received: December 16, 2013
Last Updated: February 13, 2017

Additional relevant MeSH terms:
Glioblastoma
Glioma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on June 26, 2017