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

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ClinicalTrials.gov Identifier: NCT02798406
Recruitment Status : Active, not recruiting
First Posted : June 14, 2016
Last Update Posted : March 22, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
DNAtrix, Inc.

Tracking Information
First Submitted Date  ICMJE June 9, 2016
First Posted Date  ICMJE June 14, 2016
Last Update Posted Date March 22, 2019
Study Start Date  ICMJE June 2016
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 13, 2016)
Objective response rate (ORR) [ Time Frame: 3.5 years ]
Interval tumor size reduction as measured from periodic MRI
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02798406 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 13, 2016)
  • 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
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 Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects
Official Title  ICMJE 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)
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

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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Brain Cancer
  • Brain Neoplasm
  • Glioma
  • Glioblastoma
  • Gliosarcoma
  • Malignant Brain Tumor
  • Neoplasm, Neuroepithelial
  • Neuroectodermal Tumors
  • Neoplasm by Histologic Type
  • Neoplasm, Nerve Tissue
  • Nervous System Diseases
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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
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: March 20, 2019)
49
Original Estimated Enrollment  ICMJE
 (submitted: June 13, 2016)
48
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02798406
Other Study ID Numbers  ICMJE 2401BT-002P
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Plan to share aggregate data at completion of study
Responsible Party DNAtrix, Inc.
Study Sponsor  ICMJE DNAtrix, Inc.
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Study Director: Frank Tufaro, PhD DNAtrix, Inc.
PRS Account DNAtrix, Inc.
Verification Date March 2019

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