Testing Selinexor with Temozolomide for Recurrent Glioblastoma
This study is testing a new approach for glioblastoma (a type of brain tumor) that has returned after previous treatment. It combines a drug called selinexor with the usual chemotherapy, temozolomide. Selinexor works by blocking a protein (CRM1) that helps cancer cells grow. Temozolomide damages cancer cell DNA to stop growth. The study aims to find the safest dose of selinexor with temozolomide and see how well this combination works compared to temozolomide alone. You may be able to join if you are 18 or older and have recurrent glioblastoma that is IDH wild-type and MGMT promoter methylated. The study will measure how long patients live without their cancer getting worse. The current status of this study is unclear.
- Study design
- This is a Phase I/II interventional study. It will enroll 97 participants and compare the combination of selinexor and temozolomide to temozolomide alone.
- What's involved
- Participants will undergo blood sample collection and Magnetic Resonance Imaging (MRI). You will receive either selinexor and temozolomide, or a placebo and temozolomide, taken by mouth.
- Compensation
- Not stated in the trial record.
- Follow-up
- The study will assess how long you live without your disease getting worse for up to 3 years.
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NCT05432804
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recruiting
PHASE1Ages 18+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~97 participants
Updated 2026-08-26 on ClinicalTrials.gov
What's tested:Biospecimen CollectionMagnetic Resonance ImagingPlacebo AdministrationSelinexorTemozolomide
At a glance
Recruiting sites
27 of 36 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Recommended phase 2 dose (RP2D) (Phase I)
Measured over Up to 28 days
+1 more outcome measured
Conditions
Where it's being run
36 sites across 17 statesCalifornia6
Florida5
New Jersey3
New York3
Ohio3
Georgia2
Illinois2
Virginia2
Study leadership
- Jana L Portnow · PRINCIPAL_INVESTIGATOR · City of Hope Comprehensive Cancer Center LAO
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
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
What this trial measures
- Recommended phase 2 dose (RP2D) (Phase I)Up to 28 days
Any eligible patient who receives at least one dose of protocol-defined therapy will be considered evaluable for dose-limiting toxicity (DLT) if either of the following occurs: (1) the patient experiences a DLT during cycle 1 of therapy; or (2) the patient receives at least 4 doses of temozolomide and 1 dose of selinexor. All other patients enrolled during the phase 1 portion of the study will be considered inevaluable for DLT and may be replaced for the purposes of establishing the RP2D.
- Progression-free survival (PFS) (Phase II)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
Patients who experience disease progression or death will be considered to have experienced a PFS-event; otherwise the patient is considered censored at last contact.