Selinexor (KPT-330) in Combination With Temozolomide and Radiation Therapy in Patients With Newly Diagnosed Glioblastoma

A Phase I Clinical Trial of Selinexor (KPT-330) in Combination With Temozolomide and Radiation Therapy in Patients With Newly Diagnosed Glioblastoma

Background:

Glioblastoma is a type of brain cancer. Treatments include radiation, chemotherapy, and surgery. But survival rates are poor. Researchers think that the drug selinexor, when combined with chemotherapy and radiation, might help.

Objective:

To learn the highest dose of selinexor that people with brain cancer can tolerate when given with temozolomide and radiation therapy.

Eligibility:

People ages 18 and older with brain cancer that has not been treated with chemotherapy or radiation.

Design:

Participants will be screened under another protocol.

Before participants start treatment, they will have tests:

Neurological and physical evaluations

Blood and urine tests

Possible computed tomography (CT) scan or magnetic resonance imaging (MRI) of the brain if they have not had one in 3 weeks. Participants will lie in a machine that takes pictures of the body. They may have a dye injected into a vein.

Surveys about their well-being

Participants will have radiation to the brain for up to 6 weeks. This will usually be given once a day, Monday through Friday.

Starting the second day of radiation, participants will take selinexor by mouth once a week. They will take it in weeks 1, 2, 4, and 5. The timing may be changed.

Starting the first day of radiation, participants will take temozolomide by mouth once a day until they complete radiation.

Participants will have blood tests once per week during treatment.

Participants will have a follow-up visit 1 month after they complete treatment. Then they will have visits at least every 2 months for the first 2 years, then at least every 3 months for another year. Visits will include MRIs and blood tests.

Study Overview

• Status: Active, not recruiting
• Conditions: Glioblastoma; Gliosarcoma; Newly Diagnosed
• Intervention / Treatment: Drug: Selinexor; Radiation: Generic Radiation therapy (RT); Drug: Temozolomide; Other: Selective serotonin receptor (5-HT3) antagonists; Other: Olanzapine; Dietary supplement: Salt tablets; Other: Anti-diarrheal

Detailed Description

Background:

• Although radiation has been shown to improve outcomes in patients with glioblastoma (GBM), median survival remains poor. Even with the addition of temozolomide (TMZ) to surgical resection and radiotherapy, most GBMs will recur in field or adjacent to the high dose radiation volume.
• High rates of local failure indicate that GBM cells in situ are relatively radioresistant and that the effectiveness of GBM radiotherapy would benefit from additional radiosensitization.
• Selinexor has recently been shown to enhance the radiosensitivity of glioma cells both in vitro and in vivo.

Objectives:

-Assess the safety, tolerability, and maximum tolerated dose of selinexor when combined with temozolomide and radiotherapy in patients with newly diagnosed glioblastoma and gliosarcoma.

Eligibility:

• Men and women greater than 18 years old
• Histologically confirmed newly diagnosed glioblastoma or gliosarcoma
• Karnofsky Performance Scale (KPS) greater than or equal to 70
• Patients who have not previously been treated with chemotherapy or radiation therapy

Design:

• This is a Phase I trial to determine the safety and tolerability of selinexor in combination with external beam radiation therapy (RT) and temozolomide in patients with newly diagnosed glioblastoma or gliosarcoma using a "3 plus 3 design" and three dose escalation levels, with 3 patients per dose level (provided no dose limiting toxicity (DLT), a maximum of 21 patients will be enrolled.
• Patients will be treated with external beam radiation therapy in a standard manner with temozolomide given daily during radiation. Selinexor will be administered concurrent with the RT/temozolomide.
• We anticipate accrual of 21 evaluable patients which will take approximately 2 years. The accrual ceiling has been set to 24 patients.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• INCLUSION CRITERIA:

  1. Histological diagnosis

     • Pathologically confirmed glioblastoma or gliosarcoma (including astrocytoma, grade IV)
  2. Patients must be eligible for definitive external beam radiotherapy and temozolomide.
  3. Age >18 years. Because no dosing or adverse event data are currently available on the use of Selinexor in combination with Temodar in patients <18 years of age, children are excluded from this study.
  4. Patients should have a Karnofsky performance scale (KPS) greater than or equal to 70
  5. Absolute neutrophil count (ANC) >1.5x10^9/L; platelet count >100x10^9/L; and hemoglobin (Hb) >9.0 g/dL. Note: the use of transfusion or other intervention prior to cycle 1 day 1 to achieve Hb >9.0 g/dL is acceptable.
  6. Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.
  7. The effects of Selinexor on the developing human fetus are unknown. For this reason and because Selinexor agents as well as other therapeutic agents used in this trial 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, for the duration of study treatment and for one month after treatment. 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.

  8. Patients must have had surgery and/or biopsy not greater than 8 weeks prior to initial evaluation to be eligible for this study.

     EXCLUSION CRITERIA:

  1. Patients who are receiving any other investigational agents and have had prior therapy including:

     • Patients who have previously received radiation therapy (RT) to the brain.
     • Patients who received chemotherapy for the treatment of their glioma
     • Patients who are being treated with implanted Gliadel wafers
     • Patients who are being treated with tumor treating fields.
  2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to selinexor or temozolomide used in study.

  3 Patients 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 (DVT) or pulmonary embolism (PE) is not exclusionary.

  4. Patients with active uncontrolled or suspected infections

  5. Patients with severe liver dysfunction defined as:

  • Total bilirubin > 1.5 x upper limit of normal (ULN) Note: Subjects with Gilberts syndrome should not be excluded as long as total bilirubin is < 3.0 x ULN and documentation to support diagnosis is available.
  • Serum glutamate pyruvate transaminase (SGPT) or called as Alanine aminotransferase (ALT) greater than or equal to 3 x ULN = 135 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L
  • Serum glutamic oxaloacetic transaminase (SGOT) or called as Aspartate aminotransferase (AST) greater than or equal to 3 x ULN = 150 U/L; for the purpose of this study, the ULN for SGOT is 50 U/L

  • Serum albumin greater than or equal to 2 x ULN

    6. Known active hepatitis A, B, or C infection

    7. Human immunodeficiency virus (HIV) patients are not eligible because of their immunocompromised status and overlap of side effects between highly active antiretroviral therapy (HAART) and radiation therapy.

    8 Patients must not have significantly diseased or obstructed gastrointestinal tract malabsorption, uncontrolled vomiting or diarrhea, or inability to swallow oral medication.

    9. Pregnant women are excluded from this study because Selinexor could have 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, breastfeeding should be discontinued if the mother is treated with Selinexor. These potential risks may also apply to temozolomide used in this study.

    10. Patients with pre-existing known or suspected radiation sensitivity syndromes will be excluded due to potential confounding effect on outcome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 1/Experimental Therapy - Selinexor with Temozolomide and Radiation; Selinexor with temozolomide and radiation

Drug: Selinexor; Selinexor will be administered orally at an initial dose of 80 mg. The first dose will be given on day 2 of radiation and will thereafter be administered weekly on the second day of weekly radiation on weeks 1, 2, 4, and 5. If this dose level is tolerated, the dose will be escalated to 60 mg twice a week (days 1 and 4) on weeks 1,2,4,5. The third and final dose level will also be 60mg administered twice weekly for 6 weeks starting on days 1 and 4 radiation.; Other Names: Xpovio; Radiation: Generic Radiation therapy (RT); Radiation therapy (RT) will be administered daily (Monday to Friday); Drug: Temozolomide; Temozolomide will begin on the first day or evening prior of radiation and be administered orally daily at a dose of 75 mg/m^2 during the radiation treatment. Temozolomide will continue until the completion of radiation and then will be stopped. Beginning 1-month post-radiation therapy (RT), the adjuvant temozolomide will be given per standard of care.; Other Names: Temodar; Other: Selective serotonin receptor (5-HT3) antagonists; Anti-emetic for breakthrough nausea.; Other Names: Serotonin antagonists; Other: Olanzapine; 2.5mg to 5mg once a day if weight loss is rapid.; Other Names: Zyprexa; Zyprexa Zydis; Zyprexa Relprevv; Dietary supplement: Salt tablets; To treat hyponatremia, add salt tablets to participants diet per institutional guidelines.; Other Names: Sodium Chloride tablets; Other: Anti-diarrheal; Treat diarrhea with an anti-diarrheal per institutional guidelines; Other Names: Imodium; Loperamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD) of Selinexor	The MTD is the dose level at which no more than 1 of up to 6 participants experience dose limiting-toxicity (DLT) within 1 month of completion of treatment, and the dose below that at which at least 2 (of< =6) participants have DLT as a result of selinexor/radiation therapy (RT)/temozolomide.	7 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting Toxicities of Selinexor to Concurrent Radiation Therapy and Temozolomide Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) and Radiation Therapy Oncology Group (RTOG)	Dose-limiting toxicities of Selinexor to concurrent radiation therapy and temozolomide. A DLT is defined as a clinically significant adverse event assessed as unrelated to tumor progression, intercurrent illness or concomitant medications and meets any of the criteria such as any Grade 3 or 4 toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v5.0; and any Grade 3 or 4 toxicity per Radiation Therapy Oncology Group (RTOG) acute morbidity. CTCAE: Grade 3 is severe, and Grade 4 is life-threatening. RTOG: Grade 3 Brain/Central nervous system (CNS): neurologic findings present sufficient to require home care; Skin: confluent moist desquamation other than skin folds; Eye: severe keratitis; Ear: severe external otitis; and Grade 4 Brain/CNS is serious neurologic impairment; Skin: ulceration; Eye: loss of vision; and Ear: deafness.DLT's include all adverse events, including clinically significant abnormal findings on laboratory evaluations, regardless of severity.	Measured each week of treatment and up to 30 days post treatment; approximately 6-7 weeks with another month added on = ~ 11 weeks to monitor.
Dose-limiting Toxicities (DLT) Effects on Neurocognition	Define the dose-limiting toxicities effects on neurocognition in the setting of the addition of Selinexor to concurrent radiation therapy and temozolomide. A DLT is defined as a clinically significant adverse event assessed as unrelated to tumor progression, intercurrent illness or concomitant medications and meets any of the criteria such as any Grade 3 or 4 toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v5.0; and any Grade 3 or 4 toxicity per Radiation Therapy Oncology Group (RTOG) acute morbidity. DLT's include all adverse events (AE), including clinically significant abnormal findings on laboratory evaluations, regardless of severity. Evaluations completed on participants weekly or complications requiring admission to the emergency room (ER)/hospital are also included in the collection of AE's to determine if DLT.	Measured each week of treatment and up to 30 days post treatment; approximately 6-7 weeks with another month added on = ~ 11 weeks to monitor.
Dose-limiting Toxicities Effects on Quality of Life (QOL)	Define the dose-limiting toxicities (DLT) effects on quality of life (QOL) in the setting of the addition of Selinexor to concurrent radiation therapy and temozolomide. A DLT is defined as a clinically significant adverse event assessed as unrelated to tumor progression, intercurrent illness or concomitant medications and meets any of the criteria such as any Grade 3 or 4 toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v5.0; and any Grade 3 or 4 toxicity per Radiation Therapy Oncology Group (RTOG) acute morbidity. QOL life scores will be summarized. DLT's include all adverse events (AE), including clinically significant abnormal findings on laboratory evaluations, regardless of severity. Evaluations completed on participants weekly or complications requiring admission to the emergency room (ER)/hospital are also included in the collection of AEs to determine if DLT.	Measured each week of treatment and up to 30 days post treatment; approximately 6-7 weeks with another month added on = ~ 11 weeks to monitor.
Patient-Reported Outcomes Measurement Information System (PROMIS) Depression Scale	The PROMIS depression questionnaire in the setting of the addition of Selinexor to concurrent radiation therapy and temozolomide. A DLT is defined as a clinically significant adverse event assessed as unrelated to tumor progression, intercurrent illness or concomitant medications and meets any of the criteria such as any Grade 3 or 4 toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v5.0; and any Grade 3 or 4 toxicity per Radiation Therapy Oncology Group (RTOG) acute morbidity. QOL life scores from questionnaires rating symptoms on a scale of 1 (never) - 5 (very often several times a day) will be summarized. A score of 1 is the best outcome. A score of 5 is worst outcome. The difference between two timepoints - baseline and close of treatment is also reported.	Baseline and completion of treatment, up to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Serious and/or Non-Serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. All adverse events, including clinically significant abnormal findings on laboratory evaluations, regardless of severity, will be followed until return to baseline or stabilization of event.	Adverse events are documented from the first study intervention, Study Day 1, through 30 days after the subject received the last study drug administration, an average of 2.5 months.
Progression Free Survival (PFS)	PFS is defined as the time from initiation of treatment on protocol to progression as per Response Assessment in Neuro-Oncology (RANO) criteria or death due to disease progression. Progressive disease is at least two sequential scans separated by at ≥4 weeks both exhibiting ≥25% increase in sum of products of perpendicular diameters or ≥40% increase in total volume of enhancing lesions. Clear clinical deterioration not attributable to other causes apart from tumor or attributable to changes in steroid use. Failure to return for evaluation as a result of death or deteriorating condition.	From initiation of treatment on protocol to progression as per RANO criteria or death due to disease progression, approximately months
Overall Survival (OS)	OS is defined as the time from initiation of treatment on protocol to date of death due to any cause. For participants alive as of last follow-up, time to death will be censored at last contact date.	From initiation of treatment on protocol to date of death due to any cause, approximately months.
Dose-limiting Toxicities (DLT) Effects on Quality of Life (QOL) Using the MD Anderson Symptom Inventory for Brain Tumors (MDSAI-BT)	DLT effects on quality of life (QOL) using the MD Anderson Symptom Inventory for Brain Tumors (MDASI-BT) in the setting of the addition of Selinexor to concurrent radiation therapy and temozolomide. A DLT is defined as a clinically significant adverse event assessed as unrelated to tumor progression, intercurrent illness or concomitant medications and meets any of the criteria such as any Grade 3 or 4 toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v5.0; and any Grade 3 or 4 toxicity per Radiation Therapy Oncology Group (RTOG) acute morbidity. QOL life scores from questionnaires rating symptoms on a scale of 0 (symptoms not present)-10 (as bad as you can imagine) will be summarized. A score of 0 is the best outcome. A score of 10 is the worst outcome. The difference between two timepoints - baseline and close of treatment is also reported.	Baseline and close of treatment, up to 3 years
Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety Scale	The PROMIS anxiety scale in the setting of the addition of Selinexor to concurrent radiation therapy and temozolomide. A DLT is defined as a clinically significant adverse event assessed as unrelated to tumor progression, intercurrent illness or concomitant medications and meets any of the criteria such as any Grade 3 or 4 toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v5.0; and any Grade 3 or 4 toxicity per Radiation Therapy Oncology Group (RTOG) acute morbidity. QOL life scores from questionnaires rating symptoms on a scale of 1 (never) - 5 (always) will be summarized. A score of 1 is the best outcome. A score of 5 is the worst outcome. The difference between two timepoints - baseline and close of treatment is also reported.	Baseline and completion of treatment, up to 3 years
National Cancer Institute (NCI) Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)	The NCI PRO-CTCAE in the setting of the addition of Selinexor to concurrent radiation therapy and temozolomide. A DLT is defined as a clinically significant adverse event assessed as unrelated to tumor progression, intercurrent illness or concomitant medications and meets any of the criteria such as any Grade 3 or 4 toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v5.0; and any Grade 3 or 4 toxicity per Radiation Therapy Oncology Group (RTOG) acute morbidity. QOL life scores from questionnaires rating symptoms on a scale of 0 (None) - 4 (Very severe) will be summarized. A score of 0 is the best outcome. A score of 4 is the worst outcome. The difference between two timepoints - baseline and close of treatment is also reported.	Baseline and completion of treatment, up to 3 years
Neuro-quality of Life (QOL) Assessment Cognition Function	The Neuro-QOL assessment Cognition Function in the setting of the addition of Selinexor to concurrent radiation therapy and temozolomide. A DLT is defined as a clinically significant adverse event assessed as unrelated to tumor progression, intercurrent illness or concomitant medications and meets any of the criteria such as any Grade 3 or 4 toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v5.0; and any Grade 3 or 4 toxicity per Radiation Therapy Oncology Group (RTOG) acute morbidity. QOL life scores from questionnaires rating symptoms on a scale of 5 (Never) -1 (Very often-several times a day), e.g., thinking slow, will be summarized. A score of 5 is the best outcome. A score of 1 is the worst outcome. The difference between two timepoints - baseline and close of treatment is also reported.	Baseline and completion of treatment, up to 3 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Kevin A Camphausen, M.D., National Cancer Institute (NCI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2020
• Primary Completion (Actual): September 29, 2023
• Study Completion (Estimated): July 30, 2028

Study Registration Dates

• First Submitted: December 31, 2019
• First Submitted That Met QC Criteria: December 31, 2019
• First Posted (Actual): January 2, 2020

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: GBM; Radiotherapy; Gliosarcoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Gliosarcoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Pharmacologic Actions; Chemical Actions and Uses; Dacarbazine; Triazenes; Imidazoles; Piperidines; Inorganic Chemicals; Chlorine Compounds; Benzazepines; Benzodiazepines; Sodium Compounds; Chlorides; Hydrochloric Acid; Olanzapine; Temozolomide; Loperamide; Serotonin Antagonists; selinexor; Sodium Chloride; Salts
• Other Study ID Numbers: 200027; 20-C-0027

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. All collected IPD will be shared with collaborators under the terms of collaborative agreements.
• IPD Sharing Time Frame: Clinical data available during the study and indefinitely.
• IPD Sharing Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No