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

Last updated: May 19, 2025
Sponsor: National Cancer Institute (NCI)
Overall Status: Active - Not Recruiting

Phase

1

Condition

Gliomas

Astrocytoma

Glioblastoma Multiforme

Treatment

Salt tablets

Olanzapine

Anti-diarrheal

Clinical Study ID

NCT04216329
200027
20-C-0027
  • Ages > 18
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

  • INCLUSION CRITERIA:
  1. Histological diagnosis
  • Pathologically confirmed glioblastoma or gliosarcoma (includingastrocytoma, grade IV)

  1. Patients must be eligible for definitive external beam radiotherapy andtemozolomide.

  2. Age >18 years. Because no dosing or adverse event data are currently availableon the use of Selinexor in combination with Temodar in patients <18 years ofage, children are excluded from this study.

  3. Patients should have a Karnofsky performance scale (KPS) greater than or equalto 70

  4. Absolute neutrophil count (ANC) >1.5x10^9/L; platelet count >100x10^9/L; andhemoglobin (Hb) >9.0 g/dL. Note: the use of transfusion or other interventionprior to cycle 1 day 1 to achieve Hb >9.0 g/dL is acceptable.

  5. Ability of subject or Legally Authorized Representative (LAR) to understand andthe willingness to sign a written informed consent document.

  6. The effects of Selinexor on the developing human fetus are unknown. For thisreason and because Selinexor agents as well as other therapeutic agents used inthis trial are known to be teratogenic, women of child-bearing potential andmen must agree to use adequate contraception (hormonal or barrier method ofbirth control; abstinence) prior to study entry, for the duration of studytreatment and for one month after treatment. Should a woman become pregnant orsuspect she is pregnant while she or her partner is participating in thisstudy, she should inform her treating physician immediately.

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

Exclusion

EXCLUSION CRITERIA:

  1. Patients who are receiving any other investigational agents and have had priortherapy 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.
  1. History of allergic reactions attributed to compounds of similar chemical orbiologic composition to selinexor or temozolomide used in study.

3 Patients with coagulation problems and medically significant bleeding in the monthprior to start of treatment (peptic ulcers, epistaxis, spontaneous bleeding). Priorhistory of deep vein thrombosis (DVT) or pulmonary embolism (PE) is notexclusionary.

  1. Patients with active uncontrolled or suspected infections

  2. Patients with severe liver dysfunction defined as:

  • Total bilirubin > 1.5 x upper limit of normal (ULN) Note: Subjects withGilberts syndrome should not be excluded as long as total bilirubin is < 3.0 xULN and documentation to support diagnosis is available.

  • Serum glutamate pyruvate transaminase (SGPT) or called as Alanineaminotransferase (ALT) greater than or equal to 3 x ULN = 135 U/L; for thepurpose of this study, the ULN for SGPT is 45 U/L

  • Serum glutamic oxaloacetic transaminase (SGOT) or called as Aspartateaminotransferase (AST) greater than or equal to 3 x ULN = 150 U/L; for thepurpose of this study, the ULN for SGOT is 50 U/L

  • Serum albumin greater than or equal to 2 x ULN

  1. Known active hepatitis A, B, or C infection
  2. Human immunodeficiency virus (HIV) patients are not eligible because oftheir immunocompromised status and overlap of side effects between highlyactive antiretroviral therapy (HAART) and radiation therapy. 8 Patients must not have significantly diseased or obstructed gastrointestinaltract malabsorption, uncontrolled vomiting or diarrhea, or inability to swalloworal medication.
  3. Pregnant women are excluded from this study because Selinexor could havethe potential for teratogenic or abortifacient effects. Because there isan unknown but potential risk for adverse events in nursing infantssecondary to treatment of the mother with Selinexor, breastfeeding shouldbe discontinued if the mother is treated with Selinexor. These potentialrisks may also apply to temozolomide used in this study.
  4. Patients with pre-existing known or suspected radiation sensitivitysyndromes will be excluded due to potential confounding effect on outcome.

Study Design

Total Participants: 11
Treatment Group(s): 7
Primary Treatment: Salt tablets
Phase: 1
Study Start date:
July 07, 2020
Estimated Completion Date:
July 30, 2026

Study 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.

Connect with a study center

  • National Institutes of Health Clinical Center

    Bethesda, Maryland 20892
    United States

    Site Not Available

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