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

This study is currently recruiting participants.
Verified August 2017 by DNAtrix, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02798406
First Posted: June 14, 2016
Last Update Posted: August 30, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
DNAtrix, Inc.
June 9, 2016
June 14, 2016
August 30, 2017
June 2016
December 2019   (Final data collection date for primary outcome measure)
Objective response rate (ORR) [ Time Frame: 3.5 years ]
Interval tumor size reduction as measured from periodic MRI
Same as current
Complete list of historical versions of study NCT02798406 on ClinicalTrials.gov Archive Site
  • Overall survival (OS) [ Time Frame: 3.5 years ]
    Months alive following treatment as measured during periodic study visits
  • Time to tumor response [ Time Frame: 3.5 years ]
    Months to response following treatment as measured during periodic MRIs
  • Duration of response [ Time Frame: 3.5 years ]
    Months of sustained response as measured during periodic study visits
Same as current
Not Provided
Not Provided
 
Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects
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)

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

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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • 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
    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
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.
Interventions:
  • Biological: DNX-2401
  • Biological: pembrolizumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
48
June 2020
December 2019   (Final data collection date for primary outcome measure)

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
  • Tumor recurrence or progression documented after previously failing surgical resection, chemotherapy and/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

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 treatment with high-dose systemic corticosteroids within 2 weeks of the start of intravenous pembrolizumab infusions
  • Uncontrolled blood-sugar levels defined as HbA1c > 7% on 2 separate measurements
  • Previous treatment with anti-PD1 or PD-L1 agents including pembrolizumab (KEYTRUDA) or any other checkpoint inhibitor(s) (e.g., ipilimumab, nivolumab, etc.)
  • Evidence of active, non-infectious pneumonitis 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

Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact: Karen A Gammon, MS, RN kgammon@dnatrix.com
Canada,   United States
 
 
NCT02798406
2401BT-002P
Yes
Not Provided
Plan to Share IPD: Yes
Plan Description: Plan to share aggregate data at completion of study
DNAtrix, Inc.
DNAtrix, Inc.
Merck Sharp & Dohme Corp.
Study Director: Frank Tufaro, PhD DNAtrix, Inc.
DNAtrix, Inc.
August 2017

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