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

NCT04216329 | Active Not Recruiting Phase 1 Results FDA Drug

• 2 other identifiers: 20002720-C-0027
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Gliosarcoma; Newly Diagnosed; Glioblastoma

Keywords

Radiotherapy; GBM; Gliosarcoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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)

  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)

  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

  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

  Baseline and completion of treatment, up to 3 years

Other Outcomes (7)

• Dose-limiting Toxicities (DLT) Effects on Quality of Life (QOL) Using the MD Anderson Symptom Inventory for Brain Tumors (MDSAI-BT)

  Baseline and close of treatment, up to 3 years

• Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety Scale

  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)

  Baseline and completion of treatment, up to 3 years

Study Arms (1)

1/Experimental Therapy - Selinexor with Temozolomide and Radiation

EXPERIMENTAL

Selinexor with temozolomide and radiation

Drug: Selinexor; Drug: Temozolomide; Radiation: Generic Radiation therapy (RT); Other: Selective serotonin receptor (5-HT3) antagonists; Other: Olanzapine; Dietary Supplement: Salt tablets; Other: Anti-diarrheal

Interventions

Selinexor DRUG

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.

Also known as: Xpovio

1/Experimental Therapy - Selinexor with Temozolomide and Radiation

Temozolomide DRUG

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.

Also known as: Temodar

1/Experimental Therapy - Selinexor with Temozolomide and Radiation

Generic Radiation therapy (RT) RADIATION

Radiation therapy (RT) will be administered daily (Monday to Friday)

1/Experimental Therapy - Selinexor with Temozolomide and Radiation

Selective serotonin receptor (5-HT3) antagonists OTHER

Anti-emetic for breakthrough nausea.

Also known as: Serotonin antagonists

1/Experimental Therapy - Selinexor with Temozolomide and Radiation

Olanzapine OTHER

2.5mg to 5mg once a day if weight loss is rapid.

Also known as: Zyprexa Relprevv, Zyprexa Zydis, Zyprexa

1/Experimental Therapy - Selinexor with Temozolomide and Radiation

Salt tablets DIETARY_SUPPLEMENT

To treat hyponatremia, add salt tablets to participants diet per institutional guidelines.

Also known as: Sodium Chloride tablets

1/Experimental Therapy - Selinexor with Temozolomide and Radiation

Anti-diarrheal OTHER

Treat diarrhea with an anti-diarrheal per institutional guidelines

Also known as: Loperamide, Imodium

1/Experimental Therapy - Selinexor with Temozolomide and Radiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological diagnosis
• Pathologically confirmed glioblastoma or gliosarcoma (including astrocytoma, grade IV)
• Patients must be eligible for definitive external beam radiotherapy and temozolomide.
• 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.
• Patients should have a Karnofsky performance scale (KPS) greater than or equal to 70
• 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.
• Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.
• 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.
• Patients must have had surgery and/or biopsy not greater than 8 weeks prior to initial evaluation to be eligible for this study.

You may not qualify if:

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• 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.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to selinexor or temozolomide used in study.
• \. Patients with active uncontrolled or suspected infections
• \. 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
• \. Known active hepatitis A, B, or C infection
• \. 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Gliosarcoma; Glioblastoma

Interventions

selinexor; Temozolomide; Serotonin Antagonists; Olanzapine; Salts; Sodium Chloride; Loperamide

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Inorganic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Sodium Compounds; Piperidines

Results Point of Contact

• Title: Dr. Kevin A. Camphausen
• Organization: National Cancer Institute

camphauk@mail.nih.gov

240-760-6205

Study Officials

• Kevin A Camphausen, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigator

Study Record Dates

• First Submitted: December 31, 2019
• First Posted: January 2, 2020
• Study Start: July 7, 2020
• Primary Completion: September 29, 2023
• Study Completion (Estimated): July 30, 2028
• Last Updated: January 23, 2026
• Results First Posted: October 15, 2024

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• 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).

Locations

US (1)