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Brain CancerPhase 2CAPTIVENCT02798406

Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects

A Phase 2 study testing DNX-2401 and pembrolizumab in people with Brain Cancer and Brain Neoplasm, run by DNAtrix, Inc. at 15 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Brain Cancer, Brain Neoplasm, Glioma
What is being tested?
DNX-2401 and pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
15 sitesin 2 countries
Study dates
6 Oct 2016to 30 Jun 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.)
Show all 11Show fewer
  • 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

Trial locations and contacts

15 sites in 2 countries.

15 sites in 2 countries

United States14 sites

  • Lehigh Valley Health Network

    Allentown, Pennsylvania, 18103

  • Texas Oncology Austin-Midtown

    Austin, Texas, 78705

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27514

  • Northwestern University

    Chicago, Illinois, 60611

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Ohio State University James Cancer Center

    Columbus, Ohio, 43210

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Arkansas for Medical Sciences (UAMS)

    Little Rock, Arkansas, 72205

  • UCLA Medical Center

    Los Angeles, California, 90095

  • University of Minnesota Neurosurgery

    Minneapolis, Minnesota, 55455

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Weill-Cornell Medicine New York-Presbyterian

    New York, New York, 10065

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

Other trials in United States

Canada1 site

  • University Health Network

    Toronto, Ontario, M5T 2S8

Other trials in Canada

About this study

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)

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

Read the 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.

Being tested
DNX-2401, pembrolizumab
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
Medical subject headings
Brain Neoplasms, Glioma, Glioblastoma, Gliosarcoma, Neoplasms, Neuroepithelial, Neuroectodermal Tumors, Neoplasms, Nerve Tissue, Nervous System Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DNX-2401Biological

    Also called Oncolytic virus, Genetically-modified adenovirus, Delta-24, Delta-24-RGD

    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.

  • pembrolizumabBiological

    Also called KEYTRUDA, lambrolizumab, MK-3475, SCH 900475

    Sequential intravenous administration every three weeks beginning 7-9 days after Day 0/DNX-2401

Study groups in NCT02798406
Study groupRoleWhat they receive
DNX-2401 + pembrolizumabExperimentalIntratumoral 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.
Receives: Biological: DNX-2401; Biological: pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective response rate (ORR)

    Interval tumor size reduction as measured from periodic MRI

    Measured: 3.5 years

Secondary outcomes (3)

  1. Overall survival (OS)

    Months alive following treatment as measured during periodic study visits

    Measured: 3.5 years

  2. Time to tumor response

    Months to response following treatment as measured during periodic MRIs

    Measured: 3.5 years

  3. Duration of response

    Months of sustained response as measured during periodic study visits

    Measured: 3.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jun 2016 (estimated)
  2. Study start6 Oct 2016
  3. Primary completion17 Mar 2021
  4. Study completion30 Jun 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02798406
Sponsor's protocol ID
2401BT-002P
Acronym
CAPTIVE
Status last verified
Jul 2021
First submitted
9 Jun 2016
Last updated
15 Jul 2021
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes: Plan to share aggregate data at completion of study

Publications

  • Nassiri F, Patil V, Yefet LS, Singh O, Liu J, Dang RMA, Yamaguchi TN, Daras M, Cloughesy TF, Colman H, Kumthekar PU, Chen CC, Aiken R, Groves MD, Ong SS, Ramakrishna R, Vogelbaum MA, Khagi S, Kaley T, Melear JM, Peereboom DM, Rodriguez A, Yankelevich M, Nair SG, Puduvalli VK, Aldape K, Gao A, Lopez-Janeiro A, de Andrea CE, Alonso MM, Boutros P, Robbins J, Mason WP, Sonabend AM, Stupp R, Fueyo J, Gomez-Manzano C, Lang FF, Zadeh G. Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial. Nat Med. 2023 Jun;29(6):1370-1378. doi: 10.1038/s41591-023-02347-y. Epub 2023 May 15.

    PubMed 37188783

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing DNX-2401 and pembrolizumab in people with Brain Cancer and Brain Neoplasm, run by DNAtrix, Inc. at 15 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (ORR) (time frame: 3.5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02798406, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2021.

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