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Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects (CAPTIVE)

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ClinicalTrials.gov Identifier: NCT02798406
Recruitment Status : Completed
First Posted : June 14, 2016
Last Update Posted : July 15, 2021
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
DNAtrix, Inc.

Study Description
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Brief Summary:

Glioblastoma (GBM) and gliosarcoma (GS) are the most common and aggressive forms of malignant brain tumor in adults and can be resistant to conventional therapies. The purpose of this Phase II study is to evaluate how well a recurrent glioblastoma or gliosarcoma tumor responds to one injection of DNX-2401, a genetically modified oncolytic adenovirus, when delivered directly into the tumor followed by the administration of intravenous pembrolizumab (an immune checkpoint inhibitor) given every 3 weeks for up to 2 years or until disease progression.

Funding Source-FDA OOPD


Condition or disease Intervention/treatment Phase
Brain Cancer Brain Neoplasm Glioma Glioblastoma Gliosarcoma Malignant Brain Tumor Neoplasm, Neuroepithelial Neuroectodermal Tumors Neoplasm by Histologic Type Neoplasm, Nerve Tissue Nervous System Diseases Biological: DNX-2401 Biological: pembrolizumab Phase 2

Detailed Description:

In the initial phase of the study, up to 12 evaluable subjects will be enrolled in 3 dose cohorts to determine the best dose of DNX-2401, as follows:

  • Cohort 1: Single dose DNX-2401 (5e8 vp) delivered intratumorally by cannula, followed by intravenous pembrolizumab every 3 weeks (Q3W)
  • Cohort 2: Single dose DNX-2401(5e9 vp) delivered intratumorally by cannula, followed by intravenous pembrolizumab every 3 weeks (Q3W)
  • Cohort 3: Single dose DNX-2401 (5e10 vp) delivered intratumorally by cannula, followed by intravenous pembrolizumab every 3 weeks (Q3W)

Following the initial phase, up to 36 additional subjects diagnosed with recurrent glioblastoma or gliosarcoma will be enrolled to receive a single of DNX-2401 determined in the initial phase administered intratumorally followed by intravenous pembrolizumab every 3 weeks.

All subjects will return to the clinic for study follow-up visits at regular intervals for safety monitoring, MRI scans and other assessments, for up to 2 years or until disease progression. All subjects will be followed closely for safety and survival.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Multi-center, Open-label Study of a Conditionally Replicative Adenovirus (DNX-2401) With Pembrolizumab (KEYTRUDA®) for Recurrent Glioblastoma or Gliosarcoma (CAPTIVE/KEYNOTE-192)
Actual Study Start Date : October 6, 2016
Actual Primary Completion Date : March 17, 2021
Actual Study Completion Date : June 30, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: DNX-2401 + pembrolizumab
Intratumoral dose (1.0 mL) of DNX-2401 followed 7-9 days later by intravenous pembrolizumab, 200 mg, given every three weeks through 105 weeks (2 yrs.) or until progressive disease or unacceptable toxicity.
 Biological: DNX-2401
On Day 0, following brain tumor biopsy and confirmation of recurrent tumor, a single injection of DNX-2401 is administered directly into the brain tumor.
Other Names:
  • Oncolytic virus
  • Genetically-modified adenovirus
  • Delta-24
  • Delta-24-RGD

Biological: pembrolizumab
Sequential intravenous administration every three weeks beginning 7-9 days after Day 0/DNX-2401
Other Names:
  • KEYTRUDA
  • lambrolizumab
  • MK-3475
  • SCH 900475
  • Checkpoint inhibitor
  • monoclonal antibody
  • anti-PD1/PD-L1


Outcome Measures
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Primary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: 3.5 years ]
    Interval tumor size reduction as measured from periodic MRI


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: 3.5 years ]
    Months alive following treatment as measured during periodic study visits

  2. Time to tumor response [ Time Frame: 3.5 years ]
    Months to response following treatment as measured during periodic MRIs

  3. Duration of response [ Time Frame: 3.5 years ]
    Months of sustained response as measured during periodic study visits


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • A single glioblastoma or gliosarcoma tumor with histopathological confirmation for first or presenting second recurrence of glioblastoma or gliosarcoma at the time of consent
  • Gross total or partial tumor resection is not possible or not planned
  • A single measurable tumor that is at least 10.0 mm longest diameter (LDi) X 10.0 mm shortest diameter (SDi) and this tumor does not exceed 40.0 mm in LDi or SDi on Screening MRI
  • Tumor recurrence or progression documented after previously failing surgical resection, chemotherapy or radiation
  • Karnofsky performance status ≥ 70 %
  • Prior anti-tumor therapies must have been completed within time periods specified in the protocol prior to DNX-2401 injection and toxic side effects must be mild, if present
  • Demonstrate adequate organ function via specified laboratory test results

Exclusion Criteria:

  • Multiple (≥ 2) separate enhancing tumors
  • Tumor location on both sides of the brain and/or involvement that would present the risk of injecting DNX-2401 into the ventricles of the brain
  • Tumor location in the brain stem
  • Requires or, based upon history, may require treatment with high-dose systemic corticosteroids within 2 weeks of the start of intravenous pembrolizumab infusions and within 2 weeks following the first infusion of pembrolizumab
  • Uncontrolled blood-sugar levels defined as HbA1c > 7%
  • Previous treatment with any checkpoint inhibitor such as anti-PD1 or PD-L1 agents including pembrolizumab (KEYTRUDA) or any other checkpoint inhibitor(s) (e.g., ipilimumab, nivolumab, etc.)
  • History of (non-infectious) or current active pneumonitis that required steroids and/or a history of interstitial lung disease
  • Prior gene transfer therapy or prior therapy with a cytolytic virus of any type
  • Brain tumor that is not measurable on MRI or persons who are unable to have MRIs
  • Pregnant or nursing females

Note: Other protocol-defined inclusion and exclusion criteria may apply as outlined in the relevant protocol version

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02798406


Locations
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United States, Arkansas
University of Arkansas for Medical Sciences (UAMS)
Little Rock, Arkansas, United States, 72205
United States, California
UCLA Medical Center
Los Angeles, California, United States, 90095
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Minnesota
University of Minnesota Neurosurgery
Minneapolis, Minnesota, United States, 55455
United States, New Jersey
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Weill-Cornell Medicine New York-Presbyterian
New York, New York, United States, 10065
United States, North Carolina
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States, 27514
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Ohio State University James Cancer Center
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Lehigh Valley Health Network
Allentown, Pennsylvania, United States, 18103
United States, Texas
Texas Oncology Austin-Midtown
Austin, Texas, United States, 78705
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Canada, Ontario
University Health Network
Toronto, Ontario, Canada, M5T 2S8
Sponsors and Collaborators
DNAtrix, Inc.
Merck Sharp & Dohme LLC
Investigators
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Study Director: Nancy Gady, BS DNAtrix, Inc.
More Information
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Responsible Party: DNAtrix, Inc.
ClinicalTrials.gov Identifier: NCT02798406    
Other Study ID Numbers: 2401BT-002P
First Posted: June 14, 2016    Key Record Dates
Last Update Posted: July 15, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Plan to share aggregate data at completion of study
Keywords provided by DNAtrix, Inc.:
brain
Central Nervous System (CNS) diseases
Central Nervous System (CNS) neoplasms
CNS
conditionally replicative adenovirus
DNX-2401
pembrolizumab
KEYTRUDA
MK-3475
SCH 900475
lambrolizumab
neoplasm, germ cell and embryonal
neoplasm, granular and epithelial
 Alcyone
Alcyone Lifesciences
AMC
cannula
MEMS cannula
DNX-2401 + pembrolizumab
Delta-24
Delta-24-RGD
Checkpoint inhibitor
anti-PD1/PD-L1
immunotherapy
monoclonal antibody
KEYNOTE-192
Additional relevant MeSH terms:
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Adenoviridae Infections
Neoplasms
Glioblastoma
Brain Neoplasms
Gliosarcoma
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Nervous System Diseases
Astrocytoma
Glioma
Neoplasms, Germ Cell and Embryonal
 Neoplasms, Glandular and Epithelial
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
DNA Virus Infections
Virus Diseases
Infections
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action