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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.
  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: 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)

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

Information from the National Library of Medicine

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, Learn About Clinical Studies.


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
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


Contacts
Contact: Karen A Gammon, MS, RN kgammon@dnatrix.com

Locations
United States, Arkansas
University of Arkansas for Medical Sciences (UAMS) Recruiting
Little Rock, Arkansas, United States, 72205
Contact: Candi Langmaid    501-686-8274    CALangmaid@uams.edu   
Contact: Kacie Simpson    501-686-8274      
Principal Investigator: Shirley S Ong, MD         
United States, California
UCLA Medical Center Recruiting
Los Angeles, California, United States, 90095
Contact: Emese Filka    310-794-3521    efilka@mednet.ucla.net   
Contact: Stacey Green, NP    310-825-0644    SDGreen@mednet.ucla.net   
Principal Investigator: Timothy Cloughesy, MD         
United States, New Jersey
Rutgers Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Celeste Jackson, B.S.    732-235-9427    clarkce@cinj.rutgers.edu   
Contact: Karen Jackson    732-235-9835    jacksoka@cinj.rutgers.edu   
Principal Investigator: Robert D Aiken, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Mariza Daras (Brain Tumor Line), MD    212-639-6767      
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
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Cathy Schilero    216-636-9410    schilec@ccf.org   
Contact: Teresa Allison    216-444-6459    allisot@ccf.org   
Principal Investigator: Michael Vogelbaum, MD, PhD         
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, Pennsylvania
Lehigh Valley Health Network Recruiting
Allentown, Pennsylvania, United States, 18103
Contact: Yasmin Candelo, RN, BSN    610-402-0636    Yasmin_o.candelo@lvhn.org   
Contact: Dana E. Clark    610-402-9543    Dana_E.Clark@lvhn.org   
Principal Investigator: Suresh Nair, MD         
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.
Investigators
Study Director: Frank Tufaro, PhD DNAtrix, Inc.
  More Information

Responsible Party: DNAtrix, Inc.
ClinicalTrials.gov Identifier: NCT02798406     History of Changes
Other Study ID Numbers: 2401BT-002P
First Submitted: June 9, 2016
First Posted: June 14, 2016
Last Update Posted: August 30, 2017
Last Verified: August 2017
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:
Neoplasms
Glioblastoma
Gliosarcoma
Nervous System Diseases
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Adenoviridae Infections
Brain Neoplasms
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
Antibodies, Monoclonal
Pembrolizumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents