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
Astrocytome+18
+ Maladies du cerveau
+ Néoplasmes cérébraux
Étude thérapeutique
Résumé
Date de début de l'étude : 6 octobre 2016
Date à laquelle le premier participant a commencé l'étude.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.
Protocole
Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.49 participants à inclure
Nombre total de participants que l'essai clinique vise à recruter.Traitement
Éligibilité
Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.Tout sexe
Le sexe biologique des participants éligibles à s'inscrire.À partir de 18 ans
Tranche d'âge des participants éligibles à participer.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Conditions
Pathologie
Critères
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
Plan de l'étude
Découvrez tous les traitements administrés dans cette étude, leur description détaillée et ce qu'ils impliquent.Un seul groupe d'intervention est désigné dans cette étude
Cette étude ne comporte pas de groupe placebo.
Groupes de traitement
Groupe I
ExpérimentalObjectifs de l'étude
Objectifs principaux
Objectifs secondaires
Centres d'étude
Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.Cette étude comporte 15 sites
University of Arkansas for Medical Sciences (UAMS)
Little Rock, United StatesOuvrir University of Arkansas for Medical Sciences (UAMS) dans Google MapsUCLA Medical Center
Los Angeles, United StatesNorthwestern University
Chicago, United StatesUniversity of Minnesota Neurosurgery
Minneapolis, United States