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

  • STATUS
    Recruiting
  • End date
    Jan 24, 2023
  • participants needed
    474
  • sponsor
    Karyopharm Therapeutics Inc
Updated on 24 April 2022
platelet count
cancer
corticosteroids
measurable disease
MRI
neutrophil count
blood transfusion
bevacizumab
carmustine
recurrent disease
temozolomide
brain tumor
recurrent glioblastoma
lomustine
renal function test
methylated
ccnu

Summary

This is a Phase 1/2 study of selinexor in combination with standard of care (SoC) therapy for newly diagnosed glioblastoma (nGBM) or recurrent glioblastoma (rGBM). This study will be conducted in 2 phases: a Phase 1a dose finding study followed by Phase 1b (dose expansion) and a Phase 2 randomized efficacy exploration study and will independently evaluate 3 different combination regimens in 3 treatment arms in patients with nGBM (Arms A and B) or with rGBM (Arm C).

  • Arm A: evaluating the combination of selinexor with radiation therapy (S-RT) in nGBM participants with uMGMT
  • Arm B: evaluating the combination of selinexor with radiation therapy and temozolomide (TMZ) (S-TRT) in nGBM participants with methylated-O6-methylguanine-DNA-methyltransferase (mMGMT)
  • Arm C: evaluating the combination of selinexor with lomustine (or carmustine, if lomustine is not available) (S-L/C) in rGBM participants regardless of MGMT status
  • Arm D: evaluating the combination of selinexor with bevacizumab in rGBM participants regardless of MGMT status
  • Arm E: evaluating the combination of selinexor with tumor treating fields (TTField) in rGBM participants regardless of MGMT status

Details
Condition Glioblastoma Multiforme
Treatment bevacizumab, carmustine, Selinexor, Temozolomide (TMZ), Lomustine (CCNU), Standard Fractionated Radiation therapy (RT), TTField
Clinical Study IdentifierNCT04421378
SponsorKaryopharm Therapeutics Inc
Last Modified on24 April 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Written informed consent in accordance with federal, local, and institutional guidelines
Age ≥18 years at the time of informed consent and ≥22 year for Arm E
Pathologically confirmed glioblastoma (including all histological variants; documentation to be provided) that are newly diagnosed (for Arms A and B) or relapsed disease (for Arm C, D and E) after 1 to 2 line of systemic therapy (RT ± TMZ or RT ± TMZ in combination with other drug) (surgical resection of recurrent disease allowed). For Arms A and B, MGMT status should be available
Arms A and B: participants who have not received RT or any systemic therapy for brain tumor and must be eligible for definitive external beam RT and TMZ
Arm C, D and E: participants must have received prior treatment with RT with or without TMZ and only 1 prior line of therapy (RT ± TMZ in combination with other drug is allowed)
Prior therapy
Measurable disease according to RANO/modified RANO guidelines is required only for Arm
Participants enrolling into Arms C, D, and E must be on a stable or decreasing dose of corticosteroids (or none) for at least 5 days prior to the baseline magnetic resonance imaging (MRI)
C, D and E; it is not required for Arms A or B
Karnofsky Performance Score (KPS) ≥70 (for Arms A and B) and 60 (for Arms C, D, and E)
Participants must have adequate organ function ≤2 weeks of study treatment as defined by the following laboratory criteria
Hematological function ≤7 days prior to Cycle 1 Day 1 (C1 D1): Absolute neutrophil count (ANC) ≥1.5 _10^9 per Liter (/L); platelet count ≥150_ 10^9/L; and hemoglobin (Hb) ≥10.0 gram per deciliter (g/dL). Transfusion is not allowed within 7 days prior to C1 D1
Hepatic function: bilirubin ≤2 _the upper limit of normal (ULN), alanine transaminase (ALT) ≤2.5_ ULN, aspartate transaminase (AST) ≤2.5 _ULN; unless bilirubin elevation is related to Gilbert's Syndrome for which bilirubin must be <4_ULN
Renal function: calculated (Cockcroft-Gault) or measured creatinine clearance ≥30 milliliter per minute (mL/min)
Fertile male participants who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 6 months following the last dose of study treatment
Female participants of childbearing potential must have a negative serum pregnancy
test at Screening and agree to use highly effective methods of contraception
throughout the study and for 6 months following the last dose of study
Limited to supratentorial disease for Arm E only
treatment
For Arms A and B: participants must have had surgery and/or biopsy not greater than [>] 8 weeks prior to initial screening
Participants must consent to provide tumor tissue and blood samples to be used for future molecular testing for correlative studies

Exclusion Criteria

Participants who are receiving any other investigational agents and /or have had prior therapy including
For Arms A and B only
Participants who have previously received RT to the brain
Participants who received chemotherapy for the treatment of their glioma
For Arms C, D, and E
Participants who are being treated with implanted Gliadel wafers
For Arm C
Prior nitrosoureas
<4 weeks from prior TMZ or other chemotherapy, or <4 weeks or 5 half-lives (whichever is shorter) for investigational agents prior to start of study treatment
Prior treatment bevacizumab or other direct Vascular endothelial growth factor/Vascular endothelial growth factor receptor (VEGF/VEGFR) inhibitors. For any questions of the definition of a direct VEGF/VEGFR inhibitor, consult the study Medical Monitor
Any AE which has not recovered to Grade <=1, or returned to baseline, related to the previous GBM therapy, except alopecia, and some other Grade 2 AEs that have been stabilized (upon Medical Monitor approval)
History of allergic reactions attributed to compounds of similar chemical or biological composition to selinexor or other study treatment
Participants must not have significantly diseased or obstructed gastrointestinal tract malabsorption, uncontrolled vomiting or diarrhea, or inability to swallow oral medication
Participants with mutated isocitrate dehydrogenase (IDH) should be excluded for Phase 2
Currently pregnant or breastfeeding
Participants who are being treated or plan to be treated during this study with TTField for participants in Arms A to D
For Arms A and B: participants with pre-existing known or suspected radiation sensitivity syndromes will be excluded due to potential confounding effect on outcome
Major surgery <2 weeks prior to the start of study treatment for Arms A to C and E, <4 weeks for Arm D
Any life-threatening illness, active medical condition, organ system dysfunction, or serious active psychiatric issue which, in the Investigator's opinion, could compromise the participant's safety or the participant's ability to remain compliant with study procedures
Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to first dose of study treatment; however, prophylactic use of these agents is acceptable even if parenteral
Participants with coagulation problems and medically significant bleeding in the month prior to start of treatment (peptic ulcers, epistaxis, intracranial hemorrhage, spontaneous bleeding). Prior history of deep vein thrombosis or pulmonary embolism is not exclusionary
For participants in Arm C, Forced Vital Capacity (FVC) or Carbon Monoxide Diffusing Capacity (DLCO) below 70% of predicted
For Arm E: implanted active electronic medical devices such as programmable intraventricular shunts, spinal cord, vagus nerve or deep brain stimulators, pacemakers or implantable automatic defibrillators, skull defect (i.e. missing bone with no replacement), sensitivity to conductive hydrogels as used in electrocardiograms (ECGs), an underlying serious scalp condition that may interfere with placement of arrays, or bullet fragments, or documented clinically significant arrhythmias
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