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Trial record 6 of 21 for:    Recruiting, Enrolling by invitation Studies | Interventional Studies | glioma | United States | First posted from 04/01/2019 to 07/31/2019

Oncolytic Adenovirus DNX-2401 in Treating Patients With Recurrent High-Grade Glioma

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ClinicalTrials.gov Identifier: NCT03896568
Recruitment Status : Recruiting
First Posted : April 1, 2019
Last Update Posted : April 1, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE March 28, 2019
First Posted Date  ICMJE April 1, 2019
Last Update Posted Date April 1, 2019
Actual Study Start Date  ICMJE February 12, 2019
Estimated Primary Completion Date February 28, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 28, 2019)
  • Maximum-tolerated dose (MTD) [ Time Frame: Up to 28 days ]
    The MTD will be defined as the dose below the dose that results in greater than or equal to one-third of the subjects exposed who experienced grade 3 or 4 (except hematological, grade 4 required) toxicity according to National Cancer Institute Common Toxicity Criteria that is deemed to be at least "probably related" to the study drug (i.e., dose-limiting toxicity [DLT]).
  • Incidence of adverse events (AEs) [ Time Frame: Up to 1 year ]
    AEs will be summarized both overall and by dose group and tabulated by severity, relationship to BM-hMSCs-DNX 2401and causality. The number and percentage of subjects experiencing AEs will be tabulated by body system/preferred term both overall and by dose group. When an AE occurs more than once, the maximum severity and causality will be counted.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: March 28, 2019)
  • Tumor response [ Time Frame: Up to 1 year ]
    Will be based upon change in tumor size by serial magnetic resonance imaging scans post injection.
  • Time to progression [ Time Frame: Up to 1 year ]
  • Virus replication in tumor [ Time Frame: Up to 1 year ]
    Detection of replicating delta-24-RGD-4C in tumor tissue will be done by immunohistochemistry against E1A protein and hexon protein.
  • Virus shedding [ Time Frame: Up to 1 year ]
    Polymerase chain reaction of serum, nasopharyngeal secretions, and urine will be performed.
  • Immunogenicity based on adenoviral (AdV) antibodies [ Time Frame: Up to 1 year ]
    Enzyme-linked immunosorbent assay (ELISA) will be used to detect AdV antibodies in serum and virus assays to determine antibody titers (anti-AdV5 antibody immunofluorescence) will be performed.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Oncolytic Adenovirus DNX-2401 in Treating Patients With Recurrent High-Grade Glioma
Official Title  ICMJE Phase I Clinical Trial of Allogeneic Bone Marrow Human Mesenchymal Stem Cells Loaded With A Tumor Selective Oncolytic Adenovirus, DNX-2401, Administered Via Intra-Arterial Injection in Patients With Recurrent High-Grade Glioma
Brief Summary This phase I trial studies best dose and side effects of oncolytic adenovirus DNX-2401 in treating patients with high-grade glioma that has come back (recurrent). Oncolytic adenovirus DNX-2401 is made from the common cold virus that has been changed in the laboratory to make it less likely to cause an infection (such as a cold). The virus is also changed to target brain cancer cells and attack them.
Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximal tolerated dose (MTD) of allogeneic bone marrow-derived human mesenchymal stem cells (BM-hMSCs) loaded with the oncolytic adenovirus DNX-2401 (BM-hMSCs-DNX2401) administered by intra-arterial injection (i.e., transfemoral super-selective endovascular intracranial injection) in patients with recurrent glioblastoma (GBM), gliosarcoma or wild-type IDH-1 anaplastic astrocytoma.

II. To determine the local and systemic toxicity of allogeneic BM-hMSCs-DNX2401 administered by intra-arterial injection (i.e., transfemoral super-selective endovascular intracranial injection) in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma.

III. To determine at the molecular and cellular level the capacity of allogeneic BM-hMSCs-DNX2401 administered intra-arterially to home to and deliver DNX-2401 to recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma by analyzing post-treatment surgical brain tumor specimens for the expression and distribution of adenoviral proteins.

SECONDARY OBJECTIVES:

I. To assess shedding of adenovirus into the blood, sputum, and nasopharynx after intra-arterial administration of BM-hMSCs-DNX2401 in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma.

II. To assess the development of anti-adenovirus antibodies after intra-arterial administration of BM-hMSCs-DNX2401 in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma.

III. To evaluate immune-mediated cytokine responses after intra-arterial administration of BM-hMSCs-DNX2401 in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma.

IV. To assess anti-tumoral activity and to determine progression-free survival (PFS) and overall survival (OS) after intra-arterial administration of BM-hMSCs-DNX2401 in patients with recurrent GBM, gliosarcoma or wild-type IDH-1 anaplastic astrocytoma.

OUTLINE: This is a dose-escalation study.

PART I: Patients receive oncolytic adenovirus Ad5-DNX-2401 intra-arterially (IA) over 20-30 minutes on day 0.

PART II: Patients receive oncolytic adenovirus Ad5-DNX-2401 as in part I. After 2 weeks, patients undergo surgery, then receive oncolytic adenovirus Ad5-DNX-2401 IA over 20-30 minutes.

After completion of study treatment, patients in part I are followed up on days 1, 4, 7, and 14 of month 1, months 1.5, 3, and 4.5, every 2 months up to month 26, month 30, then every 6 months thereafter. Patients in part II will be followed up on the day after surgery, weeks 1, 2 and 4, months 2, 2.5, 4, 5.5 and 7, every 2 months until month 19, every 4 months until month 32, then every 6 months thereafter.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • IDH1 wt Allele
  • Recurrent Anaplastic Astrocytoma
  • Recurrent Glioblastoma
  • Recurrent Gliosarcoma
  • Recurrent Malignant Glioma
Intervention  ICMJE
  • Biological: Oncolytic Adenovirus Ad5-DNX-2401
    Given IA
    Other Names:
    • Ad5-Delta24RGD
    • DNX-2401
    • DNX2401
    • Oncolytic Ad5-Delta 24RGD
    • Oncolytic Adenovirus Ad5-Delta 24RGD
  • Procedure: Therapeutic Conventional Surgery
    Undergo surgery
Study Arms  ICMJE
  • Experimental: Part I (oncolytic adenovirus Ad5-DNX-2401)
    Patients receive oncolytic adenovirus Ad5-DNX-2401 IA over 20-30 minutes on day 0.
    Intervention: Biological: Oncolytic Adenovirus Ad5-DNX-2401
  • Experimental: Part II (oncolytic adenovirus Ad5-DNX-2401, surgery)
    Patients receive oncolytic adenovirus Ad5-DNX-2401 as in part I. After 2 weeks, patients undergo surgery, then receive oncolytic adenovirus Ad5-DNX-2401 IA over 20-30 minutes.
    Interventions:
    • Biological: Oncolytic Adenovirus Ad5-DNX-2401
    • Procedure: Therapeutic Conventional Surgery
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 28, 2019)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 28, 2020
Estimated Primary Completion Date February 28, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects must be willing and able to provide informed consent, undergo and comply with all study assessments and adhere to the protocol schedule
  • Patients with recurrent malignant GBM or gliosarcoma will be eligible. Patients with recurrent anaplastic astrocytoma with wild-type IDH-1 gene will also be eligible if there is a significant enhancing mass on magnetic resonance imaging (MRI) because their prognosis/behavior is similar to GBM. A pathology report constitutes adequate documentation of histology for study inclusion. Subjects with an initial diagnosis of a lower grade glioma are eligible if a subsequent biopsy is determined to be GBM and there is a significant enhancing mass on MRI
  • Patients must show unequivocal evidence for tumor recurrence or progression by MRI scan after failing prior surgical resection, biopsy, chemotherapy or radiation. A baseline MRI must be performed within 24 days prior to registration. Biopsy is encouraged at the time of recurrence if it is unclear that there is recurrent tumor. However, biopsy is not required if the practicing physician thinks that there is adequate radiographic and clinical evidence for recurrence
  • Patients must be able to undergo endovascular treatment based on Doppler studies showing internal carotid artery (ICA) that is less than 50% occluded
  • For patients undergoing resection for biological endpoints, tumors must be surgically resectable at the time of baseline evaluation and craniotomy for tumor resection would be part of their standard medical care
  • Tumors must be > 1.0 cm in diameter with upper limit of 5 cm maximal diameter
  • Patients must have a Karnofsky performance score >= 70
  • Patients must have a life expectancy of at least 16 weeks
  • Absolute granulocyte count >= 1,500 prior to starting therapy
  • Platelet count of >= 75,000 prior to starting therapy
  • Serum glutamate pyruvate transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) < 2 times institutional normal ranges prior to starting therapy
  • Bilirubin < 2 times institutional normal ranges prior to starting therapy
  • Creatinine < 2.0 times institutional normal prior to starting therapy
  • Prothrombin time (PT), partial thromboplastin time (PTT), and thrombin time within institutional normal limits after correction of nutritional deficiencies that may contribute to prolonged PT/PTT
  • Subjects who have received the following chemotherapies must have completed them within the following time periods prior to baseline/day 0 of hMSC-DNX2401 delivery with recovery from any drug-related toxic effects to grade 1, or less, severity: 4 weeks from cytotoxic agents (3 weeks from procarbazine or temozolomide, 2 weeks from vincristine), 6 weeks from nitrosoureas (lomustine [CCNU], carmustine [BCNU]), 4 weeks from any investigational agent, 1 week from non-cytotoxic agents
  • Patients must be 8 weeks from radiotherapy to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, or 4 weeks if a new lesion, relative to the pre-radiation MRI, develops that is outside the primary radiation field (beyond 80% isodose line). However, if a biopsy is undertaken prior to these times and this biopsy documents histological evidence for recurrent disease, then patients will be eligible regardless of the time after radiation
  • Patients must be willing to forego other cytotoxic and non-cytotoxic drug or radiation therapy against the tumor while enrolled in the study
  • Women of childbearing potential must have a negative urine pregnancy test documented within 7 days prior to study initiation
  • Subjects and their partners must be willing to use effective birth control during the study and for up to 6 months following administration of hMSC-DNX2401. Birth control that is acceptable to use in this study:

    • Using twice the normal protection of birth control (i.e., double-barrier) by using a condom AND spermicidal jelly or foam, or a diaphragm AND spermicidal jelly or foam. A spermicidal jelly or foam must be used in addition to a barrier method (e.g., condom or diaphragm)
    • Birth control pills ("The Pill")
    • Depot or injectable birth control
    • IUD (intrauterine device)
    • Birth control patch (e.g., Ortho Evra)
    • NuvaRing
    • Surgical sterilization (i.e., tubal ligation or hysterectomy for women or vasectomy for men)

Exclusion Criteria:

  • Histology other than astrocytoma grade IV (GBM or gliosarcoma), although astrocytoma grade III that is IDH-1 wild-type will be included
  • Tumor foci detected below the tentorium or beyond the cranial vault
  • Tumor within the posterior fossa
  • Tumor with leptomeningeal spread
  • Difficulty in obtaining vascular access for percutaneous procedure
  • Ipsilateral carotid stenosis (> 50%, by Doppler studies)
  • Thrombophilias or primary hematological diseases
  • Transfusions or medications (G-CSF) to treat pancytopenia or other hematological conditions < 28 days prior to baseline/day 0/hMSC-DNX2401 administration
  • Biologic/immunotherapy within 2 weeks of baseline
  • Clinical or laboratory evidence of inflammatory and/or autoimmune disorders
  • Any contraindication for undergoing MRI such as: individuals with pacemakers, epicardial pacer wires, infusion pumps, surgical and/or aneurysm clips, shrapnel, metal prosthesis, implants with potential magnetic properties, metallic bodies in the eyes, etc. In addition, subjects must present with tumor that is evaluable by MRI
  • Pregnant or nursing females
  • Evidence of active uncontrolled infection or unstable or severe intercurrent medical conditions. All subjects must be afebrile at baseline (i.e., < 38.0 degrees Celsius [C])
  • Any medical condition that precludes surgery or endovascular treatment
  • Alcoholism (dependency), alcohol or substance abuse within twelve (12) months prior to screening that has caused health consequences
  • Immunocompromised subjects or those with autoimmune conditions, active hepatitis (liver function tests > 2x normal) or human immunodeficiency virus (HIV) seropositivity
  • Evidence of bleeding diathesis or use of anticoagulant medication or any medication that may increase the risk of bleeding that cannot be stopped prior to surgery. If the medication can be discontinued prior to DNX-2401 injection then the subject may be eligible following consultation with the study chair. Low weight heparin and Lovenox (enoxaparin) administered on a temporary limited basis for post procedure deep venous thrombosis (DVT) prophylaxis is permitted
  • History or current diagnosis of any medical or psychological condition that in the investigator's opinion, might interfere with the subject's ability to participate or inability to obtain informed consent because of psychiatric or complicating medical problems
  • Encephalitis, multiple sclerosis or other central nervous system (CNS) infection or primary CNS disease that would interfere with subject evaluation
  • Subjects with known Li-Fraumeni syndrome or with a known germ line deficit in the retinoblastoma gene or its related pathways
  • Subjects with significant systemic or major illnesses including but not limited to: congestive heart failure, ischemic heart disease, cerebrovascular disease (history of strokes or transient ischemic attacks [TIAs] in large vessel or small vessel distribution), kidney disease or renal failure, active liver disease, organ transplantation, or significant psychiatric disorder
  • Enrollment in a concomitant therapeutic clinical study
  • Any condition that prevents compliance with the protocol or adherence to therapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Frederick Lang 713-792-2400 flang@mdanderson.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03896568
Other Study ID Numbers  ICMJE 2015-0953
NCI-2019-01195 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2015-0953 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
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 M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Frederick F Lang M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date March 2019

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