Selinexor (KPT-330) in Combination With Temozolomide and Radiation Therapy in Patients With Newly Diagnosed Glioblastoma
- - INCLUSION CRITERIA: 1. Histological diagnosis --Pathologically confirmed glioblastoma or gliosarcoma 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 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 within 7 days prior to enrollment. 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 DVT or PE is not exclusionary 4. Patients with active uncontrolled or suspected infections 5. Patients with severe liver dysfunction defined as: - Total bilirubin greater than or equal to 1.5 x upper limit of normal (ULN) - 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 less than or equal to 2 x ULN 6. Known active hepatitis A, B, or C infection 7. HIV patients are not eligible because of their immunocompromised status and overlap of side effects between HAART therapy 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.
- 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
- Selinexor has recently been shown to enhance the radiosensitivity of glioma cells both
in vitro and in vivo.
-Assess the safety, tolerability, and maximum tolerated dose of selinexor when combined with
temozolomide and radiotherapy in patients with newly diagnosed glioblastoma and gliosarcoma.
- 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
- 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
Trial Phase Phase I
Trial Type Treatment
National Cancer Institute
- Primary ID 200027
- Secondary IDs NCI-2020-00336, 20-C-0027
- Clinicaltrials.gov ID NCT04216329