A Study of Selinexor in Combination With Standard of Care Therapy for Newly Diagnosed or Recurrent Glioblastoma

Titre officiel

A Phase 1/2 Study of Selinexor in Combination With Standard of Care (SoC) Therapy for Newly Diagnosed or Recurrent Glioblastoma

Sommaire:

Il s’agit d’une étude multicentrique ouverte de phases I et II. Cet essai clinique comportera deux phases, soit la phase I : augmentation de la dose (étude de détermination de la dose sans répartition aléatoire) et la phase II : extension de la dose (évaluation de l’efficacité de façon aléatoire). Durant la phase I, l’étude aura pour but d’évaluer la dose maximale tolérée (DMT), la dose recommandée pour la phase II (DRP2), ainsi que l’efficacité et l’innocuité préliminaires du selinexor pris en association avec le traitement standard chez des patients atteints d’un glioblastome multiforme nouvellement diagnostiqué (GBMn) ou d’un glioblastome multiforme récidivant (GBMr) L’étude évaluera trois différents traitements d’association dans trois groupes de traitement répartis comme suit : groupe A : participants atteints d’un GBMn avec non-méthylation du promoteur du gène MGMT (O6-méthylguanine-ADN-méthyltransférase) (MGMTn); groupe B : participants avec méthylation du gène MGMT (MGMTm) et groupe C : participants atteints d’un GBMr sans égard à leur statut MGMT. La deuxième phase de l’étude visera à comparer l’association selinexor et traitement standard au traitement standard en monothérapie, dans les trois groupes de traitement.

Description de l'essai

Primary Outcome:

• Phase 1a: Maximum Tolerated Dose Per Arm: Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
• Phase 1a: Recommended Phase 2 Dose Per Arm
• Phase 1a: Number of Participants with Adverse Events (AEs) with Grade Greater Than or Equal to (>=) 3, Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation
• Phase 1b: Progressive Free Survival at 3 Months for All Arms
• Phase 1b: Overall Survival (OS) for All Arms
• Phase 2: Progression-free Survival (PFS) in Arms A and B
• Phase 2: Overall Survival (OS) for Arm C

• Phase 1a: Overall Survival (OS) for Each Arm
• Phase 1a/1b: Time to Progression (TTP) for Each Arm
• Phase 1a/1b: Progressive Free Survival (PFS) for Each Arm
• Phase 1a/1b: Overall Response Rate (ORR) Based on Modified Response Assessment in Neuro-Oncology (RANO) Criteria in Arm C, D and E
• Phase 1a/1b: Disease Control Rate (DCR) Based on Modified Response Assessment in Neuro-Oncology Criteria in Arm C, D and E
• Phase 1a/1b: Duration of Response (DOR) in Arm C, D and E
• Phase 1a/1b: Maximum Plasma Concentration (Cmax) of Selinexor
• Phase 1a/1b: Area Under the Concentration-time Curve (AUC) of Selinexor
• Phase 1a/1b: Apparent Clearance (CL) of Selinexor
• Phase 1b: Number of Participants with Adverse Events (AEs) with Grade Greater Than or Equal to (>=) 3, Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation
• Phase 1b: Maximum Tolerated Dose
• Phase 1b: Recommended Phase 2 Dose
• Phase 2: Progression Free Survival Per (PFS) as Assessed by Investigator per Modified Response Assessment in Neuro-Oncology Criteria in Arms A and B
• Phase 2: Overall Survival for Participants With Newly Diagnosed Glioblastoma Multiforme in Arms A and B
• Phase 2: Progression Free Survival (PFS) as Assessed by Independent Review Committee (IRC) per Modified Response Assessment in Neuro-Oncology Criteria in Arm C
• Phase 2: Progression Free Survival (PFS) as Assessed by Investigator per Modified Response Assessment in Neuro-Oncology Criteria in Arm C
• Phase 2: Overall Response Rate (ORR) as Assessed by IRC in Arm C
• Phase 2: Overall Response Rate (ORR) as Assessed by Investigator in Arm C
• Phase 2: Disease Control Rate (DCR) as Assessed by IRC in Arm C(TEAEs) by Severity Grade ≥3, Serious Adverse event (SAEs), and AEs Leading to Treatment Discontinuation
• Phase 2: Disease Control Rate (DCR) as Assessed by Investigator in Arm C
• Phase 2: Duration of Response (DOR) as Assessed by IRC in Arm C
• Phase 2: Duration of Response (DOR) as Assessed by Investigator in Arm C
• Phase 2: Progression Free Survival at 6 Months (PFS6) as Assessed by IRC in all Arms
• Phase 2: Progression Free Survival at 6 Months (PFS6) as Assessed by Investigator in all Arms
• Phase 2: Overall Survival Rate at 12 and 24 Months in all Arms
• Phase 2: Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) by Grade >=3, Serious Adverse event (SAEs), and AEs Leading to Treatment Discontinuation

Voir cet essai sur ClinicalTrials.gov