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

  • STATUS
    Recruiting
  • End date
    Jul 30, 2026
  • participants needed
    24
  • sponsor
    National Cancer Institute (NCI)
Updated on 23 October 2022
ct scan
platelet count
cancer
MRI
neutrophil count
glioblastoma multiforme
temozolomide
astrocytoma
gliosarcoma
brain tumor
therapeutic agent
malignant brain tumor
temodar

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 CT scan or 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.

...

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 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

Details
Condition Gliosarcoma, Newly Diagnosed, Glioblastoma
Treatment Temozolomide, Selinexor, Generic, Generic, Generic Radiation therapy (RT)
Clinical Study IdentifierNCT04216329
SponsorNational Cancer Institute (NCI)
Last Modified on23 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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

Exclusion Criteria

History of allergic reactions attributed to compounds of similar chemical or biologic
composition to selinexor or temozolomide used in study
Patients who are receiving any other investigational agents and have had prior therapy
including
aminotransferase (ALT) greater than or equal to 3 x ULN = 135 U/L; for the purpose of
Patients who have previously received radiation therapy (RT) to the brain
Patients who received chemotherapy for the treatment of their glioma
this study, the ULN for SGPT is 45 U/L
Serum glutamic oxaloacetic transaminase (SGOT) or called as Aspartate
Patients who are being treated with implanted gliadel wafers
Patients who are being treated with tumor treating fields
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
Patients with coagulation problems and medically significant bleeding in the month prior to start of treatment (peptic ulcers, epistaxis, spontaneous bleeding). Prior history of DVT or PE is not exclusionary
Serum albumin less than or equal to 2 x ULN
Patients with active uncontrolled or suspected infections
Known active hepatitis A, B, or C infection
Patients with severe liver dysfunction defined as
HIV patients are not eligible because of their immunocompromised status and overlap of
Total bilirubin greater than or equal to 1.5 x upper limit of normal (ULN)
side effects between HAART therapy and radiation therapy
Serum glutamate pyruvate transaminase (SGPT) or called as Alanine
Patients must not have significantly diseased or obstructed gastrointestinal tract
malabsorption, uncontrolled vomiting or diarrhea, or inability to swallow oral
medication
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
Patients with pre-existing known or suspected radiation sensitivity syndromes will be
excluded due to potential confounding effect on outcome
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