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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by DNAtrix, Inc.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
DNAtrix, Inc.
ClinicalTrials.gov Identifier:
NCT02798406
First received: June 9, 2016
Last updated: March 10, 2017
Last verified: March 2017
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
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)

Resource links provided by NLM:


Further study details as provided by DNAtrix, Inc.:

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


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 48
Study Start Date: June 2016
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
  • 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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02798406

Locations
United States, Arkansas
University of Arkansas for Medical Sciences (UAMS) Recruiting
Little Rock, Arkansas, United States, 72205
Contact: Shana Fetters    501-686-8274    fettersshanam@uams.edu   
Contact: Kacie Simpson    501-686-8274      
Principal Investigator: Shirley S Ong, MD         
United States, New York
Weill-Cornell Medicine New York-Presbyterian Recruiting
New York, New York, United States, 10065
Contact: Alyson Hignight    212-746-1788    alh2031@med.cornell.edu   
Contact: Mary O'Hehir    212-746-7373    mao2037@med.cornell.edu   
Principal Investigator: Rohan Ramakrishna, MD         
United States, Ohio
Ohio State University James Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Nadia Osman    614-685-2435    Nadia.Osman@osumc.edu   
Contact: Barb Kleiber    614-2931815    Barbara.Kleiber@osumc.edu   
Principal Investigator: Vinay Puduvalli, MBBS         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Sharon Ji, MD, MS    713-792-2400    xji@mdanderson.org   
Contact: Carmen Jacobs, BS, RN    713-792-2400    cjacobs@mdanderson.org   
Principal Investigator: Fred F Lang, MD         
United States, Utah
Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Karthik Sonty    801-587-5562    karthik.sonty@hci.utah.edu   
Contact: Brett Johnson    801-587-4429    brett.johnson@hci.utah.edu   
Principal Investigator: Howard Colman, MD, PhD         
Canada, Ontario
University Health Network Recruiting
Toronto, Ontario, Canada, M5T 2S8
Contact: Takyee Tung    416-603-5800 ext 5578    Takyee.Tung@uhn.ca   
Contact: Mariya Bakalets    416-946-4603    Mariya.Bakalets@uhn.ca   
Principal Investigator: Gelareh Zadeh, MD, PhD         
Sponsors and Collaborators
DNAtrix, Inc.
Merck Sharp & Dohme Corp.
  More Information

Responsible Party: DNAtrix, Inc.
ClinicalTrials.gov Identifier: NCT02798406     History of Changes
Other Study ID Numbers: 2401BT-002P
Study First Received: June 9, 2016
Last Updated: March 10, 2017
Individual Participant Data  
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:
Neoplasms
Glioblastoma
Gliosarcoma
Adenoviridae Infections
Brain Neoplasms
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Nervous System Diseases
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Astrocytoma
Glioma
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
DNA Virus Infections
Virus Diseases
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Antibodies, Monoclonal
Antibodies
Pembrolizumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents

ClinicalTrials.gov processed this record on May 25, 2017