Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluation of Ad-RTS-hIL-12 + Veledimex in Subjects With Recurrent or Progressive Glioblastoma, a Substudy to ATI001-102

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03679754
Recruitment Status : Active, not recruiting
First Posted : September 20, 2018
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
Ziopharm

Tracking Information
First Submitted Date  ICMJE August 29, 2018
First Posted Date  ICMJE September 20, 2018
Last Update Posted Date February 15, 2019
Actual Study Start Date  ICMJE September 5, 2018
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 19, 2018)
  • Safety of intratumoral Ad-RTS-hIL-12 and oral veledimex in subjects with recurrent or progressive glioblastoma based on evaluation of adverse events summarized by incidence, intensity and type of adverse event. [ Time Frame: 3 years ]
    Evaluation of adverse events as assessed by CTCAE v4.03. Adverse events will be summarized based on the incidence, intensity and type of adverse event.
  • Tolerability of intratumoral Ad-RTS-hIL-12 and oral veledimex in subjects with recurrent or progressive glioblastoma will be assessed based on expected dose compliance [ Time Frame: 3 years ]
    Evaluation will be based on expected dose compliance
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03679754 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 20, 2018)
  • Determine the overall survival (OS) of Ad-RTS-hIL-12 + veledimex [ Time Frame: 3 years ]
  • Veledimex pharmacokinetic profile: maximum plasma concentration (Cmax) [ Time Frame: 3 years ]
    The maximum plasma concentration (Cmax)
  • Veledimex pharmacokinetic profile: Time to maximum plasma concentration (Tmax) [ Time Frame: 3 years ]
    Time to maximum plasma concentration (Tmax)
  • Veledimex pharmacokinetic profile: Half-life (t1/2) [ Time Frame: 3 years ]
    Half-life (t1/2)
  • Veledimex pharmacokinetic profile: Area-under-the-concentration versus time curve (AUC) [ Time Frame: 3 years ]
    Area-under-the-concentration versus time curve (AUC)
  • Veledimex pharmacokinetic profile: Volume of distribution (Vd) [ Time Frame: 3 years ]
    Volume of distribution (Vd)
  • Veledimex pharmacokinetic profile: Clearance (CL) [ Time Frame: 3 years ]
    Clearance (CL)
  • Veledimex concentration ratio between the brain tumor and the blood [ Time Frame: 3 years ]
  • Tumor objective response rate (ORR) [ Time Frame: 3 years ]
  • Progression free survival (PFS) [ Time Frame: 3 years ]
  • Rate of pseudo-progression (PSP) [ Time Frame: 3 years ]
  • Changes from baseline in cellular responses elicited by Ad-RTS-hIL-12 and veledimex [ Time Frame: 3 years ]
    Evaluation in changes in immune cell population markers, such as, but not limited to CD3, CD4 and CD8 in peripheral blood and tumor
  • Changes from baseline in humoral immune responses elicited by Ad-RTS-hIL-12 and veledimex [ Time Frame: 3 years ]
    Evaluation of changes in levels of immunological and biological markers, such as, but not limited to IL-12 and IFN-gamma in peripheral serum samples
Original Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2018)
  • Determine the overall survival (OS) of Ad-RTS-hIL-12 + veledimex [ Time Frame: 3 years ]
  • Veledimex pharmacokinetic profile: maximum plasma concentration (Cmax) [ Time Frame: 3 years ]
    The maximum plasma concentration (Cmax)
  • Veledimex pharmacokinetic profile: Time to maximum plasma concentration (Tmax) [ Time Frame: 3 years ]
    Time to maximum plasma concentration (Tmax)
  • Veledimex pharmacokinetic profile: Half-life (t1/2) [ Time Frame: 3 years ]
    Half-life (t1/2)
  • Veledimex pharmacokinetic profile: Area-under-the-concentration versus time curve (AUC) [ Time Frame: 3 years ]
    Area-under-the-concentration versus time curve (AUC)
  • Veledimex pharmacokinetic profile: Volume of distribution (Vd) [ Time Frame: 3 years ]
    Volume of distribution (Vd)
  • Veledimex pharmacokinetic profile: Clearance (CL) [ Time Frame: 3 years ]
    Clearance (CL)
  • Veledimex concentration ratio between the brain tumor and the blood [ Time Frame: 3 years ]
  • Tumor objective response rate (ORR) [ Time Frame: 3 years ]
  • Progression free survival (PFS) [ Time Frame: 3 years ]
  • Rate of pseudo-progression (PSP) [ Time Frame: 3 years ]
  • Changes from baseline in cellular responses elicited by Ad-RTS-hIL-12 and veledimex [ Time Frame: 3 years ]
    Evaluation in changes in immune cell population makers, such as, but not limited to CD3, CD4 and CD8 in peripheral blood and tumor
  • Changes from baseline in humoral immune responses elicited by Ad-RTS-hIL-12 and veledimex [ Time Frame: 3 years ]
    Evaluation of changes in levels of immunological and biological markers, such as, but not limited: IL-12, IFN-gamma, IP-10, IL-2, IL-6 and IL-10 in peripheral serum samples
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of Ad-RTS-hIL-12 + Veledimex in Subjects With Recurrent or Progressive Glioblastoma, a Substudy to ATI001-102
Official Title  ICMJE Protocol ATI001-102 Expansion Substudy: Evaluation of Ad-RTS-hIL-12 + Veledimex in Subjects With Recurrent or Progressive Glioblastoma
Brief 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 intratumoral injection of Ad-RTS-hIL-12 given with oral veledimex.

Detailed Description

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.

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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma
Intervention  ICMJE
  • Biological: Ad-RTS-hIL-12
    • 2.0 x 10^11 viral particles (vp) per injection
    • intratumoral injection of Ad-RTS-hIL-12
  • Drug: veledimex
    • 20mg/day
    • 15 oral daily doses of veledimex
Study Arms  ICMJE Experimental: Ad-RTS-hIL-12 + veledimex
Intratumoral Ad-RTS-hIL-12 and oral veledimex
Interventions:
  • Biological: Ad-RTS-hIL-12
  • Drug: veledimex
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 12, 2019)
36
Original Estimated Enrollment  ICMJE
 (submitted: September 19, 2018)
25
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female subject ≥18 and ≤75 years of age
  • Provision of written informed consent for tumor resection, tumor biopsy, samples collection, and treatment with investigational products prior to undergoing any study specific procedures
  • Histologically confirmed glioblastoma
  • Evidence of supratentorial tumor recurrence/progression by magnetic resonance imaging (MRI) according to Response Assessment in Neuro-Oncology (RANO) criteria after standard initial therapy
  • Previous standard-of-care antitumor treatment including surgery and/or biopsy and chemoradiation. At the time of registration, subjects must have recovered from the toxic effects of previous treatments as determined by the treating physician. The washout periods from prior therapies are intended as follows: (windows other than what is listed below should be allowed only after consultation with the Medical Monitor)

    1. Nitrosureas: 6 weeks
    2. Other cytotoxic agents: 4 weeks
    3. Antiangiogenic agents: 4 weeks (NOTE: short use (< 4 doses) of bevacizumab for controlling edema is allowed)
    4. Targeted agents, including small molecule tyrosine kinase inhibitors: 2 weeks
    5. Vaccine-based therapy: 3 months
  • Able to undergo standard MRI scans with contrast agent before enrollment and after treatment
  • Karnofsky Performance Status ≥70
  • 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 upper limit of normal (ULN)
    6. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 x ULN. For subjects with documented liver metastases, ALT and AST ≤5 x ULN
    7. Total bilirubin <1.5 x ULN
    8. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) within normal institutional limits
  • Male and female subjects must agree to use a highly reliable method of birth control (expected failure rate <5% per year) from the Screening Visit through 28 days after the last dose of study drug. Women of childbearing potential (perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential) must have a negative pregnancy test at screening

Exclusion Criteria:

  • Previous treatment with bevacizumab for their disease (NOTE: short use (< 4 doses) of bevacizumab for controlling edema is allowed)
  • Subjects receiving systemic corticosteroids during the previous 4 weeks
  • Radiotherapy treatment within 4 weeks of starting veledimex
  • Subjects with clinically significant increased intracranial pressure (eg, impending herniation or requirement for immediate palliative treatment) or uncontrolled seizures
  • Known immunosuppressive disease, or autoimmune conditions, and/or chronic viral infections (eg, human immunodeficiency virus [HIV], hepatitis)
  • 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
  • Use of enzyme-inducing antiepileptic drugs (EIAED) within 7 days prior to the first dose of study drug. Note: Levetiracetam (Keppra®) is not an EIAED and is allowed
  • 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 nonmetastatic prostate cancer
  • Nursing or pregnant females
  • Prior exposure to veledimex
  • Use of medications that induce, inhibit, or are substrates of CYP4503A4 within 7 days prior to veledimex dosing without consultation with the Medical Monitor
  • Presence of any contraindication for a neurosurgical procedure
  • 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. Examples may include, but are not limited to, colitis, pneumonitis, unstable angina, congestive heart failure, myocardial infarction within 2 months of screening, and ongoing maintenance therapy for life-threatening ventricular arrhythmia or uncontrolled asthma
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03679754
Other Study ID Numbers  ICMJE ATI001-102 EXP Substudy 2.0
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ziopharm
Study Sponsor  ICMJE Ziopharm
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Arnold Gelb, MD Ziopharm Oncology Inc.
PRS Account Ziopharm
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP