Recruiting
Phase 1
Phase 2

Selinexor & Temozolomide

Sponsor:

National Cancer Institute (NCI)

Code:

NCT05432804

Conditions

Recurrent Glioblastoma, IDH-Wildtype

Recurrent MGMT-Methylated Glioblastoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Magnetic Resonance Imaging

Placebo Administration

Selinexor

Temozolomide

Study Details

Brief summary:

This phase I/II trial tests the safety, side effects and best dose of selinexor given in combination with the usual chemotherapy (temozolomide) and compares the effect of this combination therapy versus the usual chemotherapy alone (temozolomide) in treating patients with glioblastoma that has come back (recurrent). Selinexor is in a class of medications called selective inhibitors of nuclear export (SINE). It works by blocking a protein called CRM1, which may keep cancer cells from growing and may kill them. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid and may kill tumor cells and slow down or stop tumor growth. Giving selinexor in combination with usual chemotherapy (temozolomide) may shrink or stabilize the tumor better than the usual chemotherapy with temozolomide alone in patients with recurrent glioblastoma.

Conditions

Recurrent Glioblastoma, IDH-Wildtype

Recurrent MGMT-Methylated Glioblastoma

Study ID

NCT05432804

Start date

Mar 20, 2023

Status verified date

Aug, 2026

Completion date

Jun 30, 2027

Anticipated

Primary completion date

Jun 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Patients must have histologically confirmed glioblastoma (IDH wild-type, MGMT promoter methylated) that has undergone resection or biopsy upon first recurrence. Recurrence at site of prior involvement is defined by histopathological evidence of viable neoplastic cells associated with any of the following: mitotic activity, increased proliferation rate, micro-endothelial proliferation, or pseudo-palisading necrosis
  • Prior to resection or biopsy, patients must have measurable disease, defined as at least one bi-dimensional contrast-enhancing lesion with clearly defined margins, with 2 perpendicular diameters of at least 10 mm, visible on >= 2 axial slices
  • Patients must have received first-line treatment of temozolomide plus radiotherapy
  • Patients must not have received any prior therapy aside from resection or biopsy for their recurrent disease
  • Age >= 18 years. Because no dosing or adverse event data are currently available on the use of selinexor (KPT-330) in combination with temozolomide in patients < 18 years of age, children are excluded from this study
  • Karnofsky performance status >= 60% (Eastern Cooperative Oncology Group \[ECOG\] =< 2)
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 10 g/dL
  • Total bilirubin =< 2 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine transaminase (ALT) (serum glutamic-pyruvic transaminase \[SGPT\]) =< 3 x institutional ULN
  • Glomerular filtration rate (GFR) >= 30 mL/min/1.73 m\^2
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • The effects of selinexor (KPT-330) and temozolomide on the developing human fetus are unknown. For this reason and because selective nuclear export inhibitors as well as deoxyribonucleic acid (DNA) alkylating agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and for 180 days after the last dose of temozolomide. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 90 days after completion of study treatment administration
  • Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and/or family member available will also be eligible

Exclusion Criteria:

  • Patients who have had chemotherapy must have full recovery of organ and marrow function following the nadir of the last chemotherapy cycle
  • Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
  • Patients who are receiving any other investigational agents
  • Patients who have previously received bevacizumab
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to selinexor (KPT-330) or temozolomide
  • History of hypersensitivity to dacarbazine (DTIC), since both dacarbazine and temozolomide are metabolized to 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide (MTIC)
  • Patients with uncontrolled intercurrent illness
  • Pregnant women are excluded from this study because selinexor (KPT-330) is a selective inhibitor of nuclear export with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with selinexor (KPT-330), breastfeeding is not allowed for mothers during treatment with selinexor (KPT-330) and for 7 days after the last dose. These potential risks may also apply to other agents used in this study
  • Hospitalized patients with severe coronavirus disease of 2019 (COVID-19) who are >= 75 years old, or with a high-risk COVID-GRAM score, or with lactate dehydrogenase (LDH) > 370 (U/L) AND D-Dimer > 600 mcg/L FEU should not receive low-dose selinexor (KPT-330) pending additional results

Study Design

Enrollment

97 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Group I (temozolomide)

Patients receive temozolomide PO QD on days 1-5 of each cycle and placebo PO QD on days 8 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

experimental: Group II (temozolomide, selinexor)

Patients receive temozolomide PO QD on days 1-5 of each cycle and selinexor PO QD on days 8 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo MRI throughout the study and blood sample collection while on study.

Interventions

Biospecimen Collection

Undergo blood sample collection

Magnetic Resonance Imaging

Undergo MRI

Placebo Administration

Given PO

Selinexor

Given PO

Temozolomide

Given PO

Primary outcome measure

  • Recommended phase 2 dose (RP2D) (Phase I) [ Time Frame: Up to 28 days ]
  • Progression-free survival (PFS) (Phase II) [ Time Frame: From randomization to date of disease progression (either progression of existing lesions or appearance of new lesions), death, or date of last contact, whichever occurs first, assessed up to 3 years ]

Central Contacts and Locations

Locations

Mayo Clinic Hospital in Arizona

Recruiting

Phoenix, Arizona, United States, 85054

Contacts

Alyx B. Porter Umphrey

507-538-7623porter.alyx@mayo.edu

Principal Investigator:

Alyx B. Porter Umphrey

City of Hope Comprehensive Cancer Center

Recruiting

Duarte, California, United States, 91010

Contacts

Site Public Contact

800-826-4673becomingapatient@coh.org

Principal Investigator:

Jana L. Portnow

UC San Diego Moores Cancer Center

Recruiting

La Jolla, California, United States, 92093

Contacts

Site Public Contact

858-822-5354cancercto@ucsd.edu

Principal Investigator:

David E. Piccioni

University of California Davis Comprehensive Cancer Center

Recruiting

Sacramento, California, United States, 95817

Contacts

Site Public Contact

916-734-3089

Principal Investigator:

Orwa Aboud

UCHealth University of Colorado Hospital

Recruiting

Aurora, Colorado, United States, 80045

Contacts

Site Public Contact

720-848-0650

Principal Investigator:

Denise M. Damek

UM Sylvester Comprehensive Cancer Center at Coral Gables

Recruiting

Coral Gables, Florida, United States, 33146

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Macarena I. De La Fuente

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Recruiting

Deerfield Beach, Florida, United States, 33442

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Macarena I. De La Fuente

Mayo Clinic in Florida

Recruiting

Jacksonville, Florida, United States, 32224-9980

Contacts

Site Public Contact

855-776-0015

Principal Investigator:

Sani H. Kizilbash

University of Miami Miller School of Medicine-Sylvester Cancer Center

Recruiting

Miami, Florida, United States, 33136

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Macarena I. De La Fuente

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

Contacts

Site Public Contact

800-679-0775ClinicalTrials@moffitt.org

Principal Investigator:

Patrick T. Grogan

Emory University Hospital Midtown

Recruiting

Atlanta, Georgia, United States, 30308

Contacts

Site Public Contact

888-946-7447

Principal Investigator:

Kimberly Hoang

Emory University Hospital/Winship Cancer Institute

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

Site Public Contact

404-778-1868

Principal Investigator:

Kimberly Hoang

University of Chicago Comprehensive Cancer Center

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Site Public Contact

773-702-8222cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Lauren Singer

University of Chicago Medicine-Orland Park

Recruiting

Orland Park, Illinois, United States, 60462

Contacts

Site Public Contact

773-702-8222cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Lauren Singer

University of Kentucky/Markey Cancer Center

Recruiting

Lexington, Kentucky, United States, 40536

Contacts

Site Public Contact

859-257-3379

Principal Investigator:

John L. Villano

Mayo Clinic in Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Site Public Contact

855-776-0015

Principal Investigator:

Sani H. Kizilbash

Cooperman Barnabas Medical Center

Recruiting

Livingston, New Jersey, United States, 07039

Contacts

Site Public Contact

973-322-5200

Principal Investigator:

Andrew B. Brown

Rutgers Cancer Institute of New Jersey

Recruiting

New Brunswick, New Jersey, United States, 08903

Contacts

Site Public Contact

732-235-7356

Principal Investigator:

Andrew B. Brown

Laura and Isaac Perlmutter Cancer Center at NYU Langone

Recruiting

New York, New York, United States, 10016

Contacts

Site Public Contact

CancerTrials@nyulangone.org

Principal Investigator:

Jose R. McFaline Figueroa

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

Recruiting

New York, New York, United States, 10032

Contacts

Site Public Contact

212-342-5162cancerclinicaltrials@cumc.columbia.edu

Principal Investigator:

Peter C. Pan

Wake Forest University Health Sciences

Recruiting

Winston-Salem, North Carolina, United States, 27157

Contacts

Site Public Contact

336-713-6771

Principal Investigator:

Roy E. Strowd

University of Cincinnati Cancer Center-UC Medical Center

Recruiting

Cincinnati, Ohio, United States, 45219

Contacts

Site Public Contact

513-584-7698cancer@uchealth.com

Principal Investigator:

Lalanthica V. Yogendran

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Site Public Contact

800-293-5066Jamesline@osumc.edu

Principal Investigator:

Pierre Giglio

University of Cincinnati Cancer Center-West Chester

Recruiting

West Chester, Ohio, United States, 45069

Contacts

Site Public Contact

513-584-7698cancer@uchealth.com

Principal Investigator:

Lalanthica V. Yogendran

University of Oklahoma Health Sciences Center

Recruiting

Oklahoma City, Oklahoma, United States, 73104

Contacts

Site Public Contact

405-271-8777ou-clinical-trials@ouhsc.edu

Principal Investigator:

James D. Battiste

UPMC Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contacts

Site Public Contact

412-647-8073

Principal Investigator:

Megan Mantica

University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

Recruiting

Madison, Wisconsin, United States, 53718

Contacts

Site Public Contact

800-622-8922clinicaltrials@cancer.wisc.edu

Principal Investigator:

Ankush Bhatia

University of Wisconsin Carbone Cancer Center - University Hospital

Recruiting

Madison, Wisconsin, United States, 53792

Contacts

Site Public Contact

800-622-8922clinicaltrials@cancer.wisc.edu

Principal Investigator:

Ankush Bhatia

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Sep 2, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-09-02.