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

Primary Purpose

Brain Cancer, Brain Neoplasm, Glioma

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
DNX-2401
pembrolizumab
Sponsored by
DNAtrix, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Arkansas for Medical Sciences (UAMS)
  • UCLA Medical Center
  • Northwestern University
  • University of Minnesota Neurosurgery
  • Rutgers Cancer Institute of New Jersey
  • Memorial Sloan Kettering Cancer Center
  • Weill-Cornell Medicine New York-Presbyterian
  • UNC Lineberger Comprehensive Cancer Center
  • Cleveland Clinic
  • Ohio State University James Cancer Center
  • Lehigh Valley Health Network
  • Texas Oncology Austin-Midtown
  • MD Anderson Cancer Center
  • Huntsman Cancer Institute
  • University Health Network

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DNX-2401 + pembrolizumab

Arm Description

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.

Outcomes

Primary Outcome Measures

Objective response rate (ORR)
Interval tumor size reduction as measured from periodic MRI

Secondary Outcome Measures

Overall survival (OS)
Months alive following treatment as measured during periodic study visits
Time to tumor response
Months to response following treatment as measured during periodic MRIs
Duration of response
Months of sustained response as measured during periodic study visits

Full Information

First Posted
June 9, 2016
Last Updated
July 13, 2021
Sponsor
DNAtrix, Inc.
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT02798406
Brief Title
Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects
Acronym
CAPTIVE
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)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
October 6, 2016 (Actual)
Primary Completion Date
March 17, 2021 (Actual)
Study Completion Date
June 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
DNAtrix, Inc.
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Cancer, Brain Neoplasm, Glioma, Glioblastoma, Gliosarcoma, Malignant Brain Tumor, Neoplasm, Neuroepithelial, Neuroectodermal Tumors, Neoplasm by Histologic Type, Neoplasm, Nerve Tissue, Nervous System Diseases
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
DNX-2401 + pembrolizumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
DNX-2401
Other Intervention Name(s)
Oncolytic virus, Genetically-modified adenovirus, Delta-24, Delta-24-RGD
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
pembrolizumab
Other Intervention Name(s)
KEYTRUDA, lambrolizumab, MK-3475, SCH 900475, Checkpoint inhibitor, monoclonal antibody, anti-PD1/PD-L1
Intervention Description
Sequential intravenous administration every three weeks beginning 7-9 days after Day 0/DNX-2401
Primary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
Interval tumor size reduction as measured from periodic MRI
Time Frame
3.5 years
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
Months alive following treatment as measured during periodic study visits
Time Frame
3.5 years
Title
Time to tumor response
Description
Months to response following treatment as measured during periodic MRIs
Time Frame
3.5 years
Title
Duration of response
Description
Months of sustained response as measured during periodic study visits
Time Frame
3.5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nancy Gady, BS
Organizational Affiliation
DNAtrix, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of Arkansas for Medical Sciences (UAMS)
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Minnesota Neurosurgery
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Rutgers Cancer Institute of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Weill-Cornell Medicine New York-Presbyterian
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
UNC Lineberger Comprehensive Cancer Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Ohio State University James Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Lehigh Valley Health Network
City
Allentown
State/Province
Pennsylvania
ZIP/Postal Code
18103
Country
United States
Facility Name
Texas Oncology Austin-Midtown
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 2S8
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Plan to share aggregate data at completion of study

Learn more about this trial

Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects

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