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

Official Title

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

Summary:

This is a global, Phase 1/2, multicentre, open-label study. The clinical study will include of Phase 1: Dose Escalation (non-randomized, dose finding study) and Phase 2: Dose Expansion (randomized efficacy exploration). For Phase 1, the purpose of this study is to assess the maximum tolerated dose (MTD), recommend phase 2 dose (RP2D), preliminary efficacy, and safety of selinexor in combination with SoC therapy for newly diagnosed glioblastoma multiforme (GBM) (nGBM) or recurrent GBM (rGBM). The study will independently evaluate 3 different combination regimens in 3 treatment arms in participants with nGBM O6-methylguanine-DNA-methyltransferase [MGMT] promotor unmethylated [uMGMT] disease in Arm A, MGMT methylated [mMGMT]) in Arm B, and participants with rGBM regardless of MGMT status in Arm C. The second phase of the study will compare selinexor+SoC treatments versus SoC treatment alone in the three treatment Arms.

Trial Description

Primary Outcome:

• Phase 1: Maximum Tolerated Dose Per Arm: Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
• Phase 1: Recommended Phase 2 Dose Per Arm
• Phase 1: 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 2: Progression-free Survival (PFS) in Newly Diagnosed Glioblastoma Multiforme Participants in Arms A and B
• Phase 2: Overall Survival (OS) in Recurrent Glioblastoma Multiforme Participants in Arm C

• Phase 1: Overall Response Rate (ORR) Based on Modified Response Assessment in Neuro-Oncology (RANO) Criteria in Arm C
• Phase 1: Disease Control Rate (DCR) Based on Modified Response Assessment in Neuro-Oncology Criteria in Arm C
• Phase 1: Duration of Response (DOR) in Arm C
• Phase 1: Time-to-progression (TTP) Per Arm Independently
• Phase 1: Progression Free Survival Per Arm Independently
• Phase 1: Overall Survival Per Arm Independently
• Phase 1: Maximum Plasma Concentration (Cmax) of Selinexor in Plasma When Administered With Radiation Therapy, Temozolomide, and/or Lomustine
• Phase 1: Area Under the Concentration-time Curve (AUC) of Selinexor in Plasma When Administered With Radiation Therapy, Temozolomide, and/or Lomustine
• Phase 1: Apparent Clearance (CL) of Selinexor in Plasma When Administered With Radiation Therapy, Temozolomide, and/or Lomustine
• Phase 2: Overall Survival for Newly Diagnosed Glioblastoma Multiforme Participants in Arms A and B
• Phase 2: Progression Free Survival Per Modified Response Assessment in Neuro-Oncology Criteria in Participants With Recurrent Glioblastoma Multiforme Per Independent Review Committee Assessment in Arm C
• Phase 2: Progression Free Survival Per Modified Response Assessment in Neuro-Oncology Criteria in Arms A, B, and C: Per Investigator Assessment
• Phase 2: Rate of Progression Free Survival at 6-month (PFS6)
• Phase 2: Overall Response Rate Per Independent Review Committee and Investigator Assessment in Arm C
• Phase 2: Disease Control Rate Per Independent Review Committee and Investigator Assessment in Arm C
• Phase 2: Duration of Response Per Independent Review Committee and Investigator Assessment in Arm C
• Phase 2: 1 and 2-year Overall Survival Rate of Participants in Arms A, B, and C
• Phase 2: Number of Participants With Abnormalities Related to Vital Signs, Clinical Laboratory Values, and Physical Examinations
• Phase 2: Number of Participants With Any Treatment-emergent Adverse Events (AEs) (TEAEs) by Severity Grade ≥3, Serious Adverse event (SAEs), and AEs Leading to Treatment Discontinuation

View this trial on ClinicalTrials.gov