Clinical Trials /

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

NCT04216329

Description:

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. ...

Related Conditions:
  • Glioblastoma
  • Gliosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 200027
  • SECONDARY ID: 20-C-0027
  • NCT ID: NCT04216329

Conditions

  • Gliosarcoma
  • Newly Diagnosed
  • Glioblastoma

Interventions

DrugSynonymsArms
SelinexorExperimental therapy
TemozolomideExperimental therapy

Purpose

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.

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 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 once weekly
           concurrent with the RT/temozolomide.

        -  We anticipate accrual of 21 evaulable patients which will take approximately 2 years.
           The accrual ceiling has been set to 24 patients
    

Trial Arms

NameTypeDescriptionInterventions
Experimental therapyExperimentalSelinexor with temozolomide and radiation
  • Selinexor
  • Temozolomide

Eligibility Criteria

        -  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) >1.5x109/L; platelet count >100x9/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 thrombocytopenia at baseline defined as <100x109/L

          4. 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

          5. Patients with active uncontrolled or suspected infections

          6. 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 g/dL

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

          8. HIV patients are not eligible because of their immunocompromised status and overlap of
             side effects between HAART therapy and radiation therapy.

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

         10. 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.

         11. Patients with a history of concurrent second malignancy other than non-melanoma skin
             cancer or cervical cancer <3 years prior to glioblastoma or gliosarcoma diagnosis

         12. Patients with pre-existing known or suspected radiation sensitivity syndromes will be
             excluded due to potential confounding effect on outcome.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:MTD
Time Frame:7 weeks
Safety Issue:
Description:The MTD is the dose level at which no more than 1 of up to 6 patients experience DLT within 1 month of completion of treatment, and the dose below that at which at least 2 (of less than or equal to 6) patients have DLT as a result of selinexor/RT/temozolomide

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:National Cancer Institute (NCI)

Trial Keywords

  • Radiotherapy
  • GBM
  • Gliosarcoma

Last Updated

January 8, 2020