CAPTIVEA 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)
DNX-2401
+ pembrolizumab
Astrocytoma+18
+ Brain Diseases
+ Brain Neoplasms
Treatment Study
Summary
Study start date: October 6, 2016
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.49 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
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
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.One single intervention group is designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalStudy Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 15 locations
University of Arkansas for Medical Sciences (UAMS)
Little Rock, United StatesOpen University of Arkansas for Medical Sciences (UAMS) in Google MapsUCLA Medical Center
Los Angeles, United StatesNorthwestern University
Chicago, United StatesUniversity of Minnesota Neurosurgery
Minneapolis, United States