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

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Recruiting
participants needed

402
sponsor

Karyopharm Therapeutics Inc

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Updated on 19 February 2024

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blood transfusion

platelet count

corticosteroids

absolute neutrophil count

renal function

serum pregnancy test

measurable disease

gilbert's syndrome

neutrophil count

selinexor

MRI

external beam radiotherapy

systemic therapy

genetic testing

renal function test

temozolomide

recurrent disease

brain tumor

glioblastoma multiforme

recurrent glioblastoma

lomustine

methylated

ccnu

Summary

This is a global, Phase 1/2, multicenter, 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.

Details

Condition	Glioblastoma Multiforme, Glioblastoma Multiforme
Age	18-100 years
Treatment	Selinexor, Temozolomide (TMZ), Lomustine (CCNU), Standard Fractionated Radiation therapy (RT)
Clinical Study Identifier	NCT04421378
Sponsor	Karyopharm Therapeutics Inc
Last Modified on	19 February 2024

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Eligibility		Yes	No	Not Sure
Inclusion Criteria
	Participants meeting all of the following inclusion criteria are eligible to
	enroll in this
	study
	Written informed consent in accordance with federal, local, and institutional Guidelines
	Age 18 years at the time of informed consent
	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) after 1 line of systemic therapy (RT+TMZ or RT+TMZ in combination with other drug) that have not received the second line systemic treatment for relapsed disease (surgical resection of recurrent disease allowed)
	Prior therapy
	Arms A and B: participants who have not received radiation or any systemic therapy for brain tumor and must be eligible for definitive external beam radiotherapy and temozolomide
	Arm C: participants must have received prior treatment with radiation therapy and temozolomide (RT+TMZ in combination with other drug is allowed)
	Measurable disease according to modified RANO guidelines
	Participants enrolling 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)
	Karnofsky Performance Score (KPS) 70 (for Arms A and B) and 60 (for Arm C)
	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: 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 Cycle 1 Day 1
	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)
	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 2 weeks following the last dose of study treatment
	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 4 months following the last dose of study 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 genetic testing for correlative studies
Exclusion Criteria
	Participants meeting any of the following exclusion criteria are not eligible
	to enroll in this study
	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
	Participants who are being treated with implanted Gliadel wafers
	Participants who are being treated or plan to be treated during this study with tumor treating fields
	For Arm C
	<6 weeks from nitrosourea, <4 weeks from prior temozolomide or other chemotherapy or investigational agents prior to start of study treatment
	Prior treatment bevacizumab or other direct vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (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
	Major surgery <2 weeks prior to the start of study treatment
	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 coagulation problems and medically significant bleeding in the month prior to start of treatment (peptic ulcers, epistaxis, spontaneous bleeding). Prior history of deep vein thrombosis or pulmonary embolism is not exclusionary
	Currently pregnant or breastfeeding
	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
	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
	Inability to swallow tablets, malabsorption syndrome, or any other gastrointestinal disease or dysfunction that could interfere with absorption of study treatment
	In the opinion of the Investigator, participants who are significantly below their ideal body weight

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