Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Temozolomide

Lomustine

Carmustine

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Participants with nGBM uMGMT will receive 60 to 80 milligram (mg) of selinexor oral tablet once weekly (QW) across dose level -1, 1, 2, and 3 in combination with 2 Gray (Gy) radiation therapy (RT) daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 80 mg of selinexor oral tablet on Day 1 and 15 in a 28-day Cycle 2 and subsequently will continue at 80 mg QW until progressive disease (PD) during adjuvant therapy period.

Participants with nGBM uMGMT will receive 75 milligram per meter square (mg/m\^2) of temozolomide oral capsule once daily (QD) in combination with 2 Gy RT daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 150 mg/m\^2 (started from Cycle 3) and increase to 200 mg/m\^2 as tolerated per Investigator's judgment, daily for 5 days in a 28-day cycle during Cycles 4 to 8 cycles during adjuvant therapy period.

Participants with nGBM mMGMT will receive 40-80 mg of selinexor oral tablet QW across dose level -1, 1, 2, 2a, 2b and 3a and 75 mg/m\^2 of temozolomide oral capsule QD in combination with 2 Gy RT daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 60 mg (dose level 2a) or 80 mg (dose level 2b and 3a) of selinexor oral tablet on Day 1 and 15 in a 28-day Cycle 2, followed by 150 mg/m\^2 (started from Cycle 3) and increase to 200 mg/m\^2 as tolerated per Investigator's judgment, daily for 5 days in a 28-day cycle during Cycle 4 to 8 during adjuvant therapy period. Participants will continue selinexor weekly per dose level assigned until PD.

Participants with nGBM mMGMT will receive 75 mg/m\^2 of temozolomide oral capsule QD in combination with 2 Gy RT daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 150 mg/m\^2 (started from Cycle 3) and increase to 200 mg/m\^2 as tolerated per Investigator's judgment, daily for 5 days in a 28-day cycle during Cycles 4 to 8 during adjuvant therapy period.

Participants with rGBM uMGMT or mMGMT will receive 40-80 mg of selinexor oral tablet QW across dose level -1, 1, 2, 2a, and 3 and 90-110 mg/m\^2 of lomustine or 150-200 mg/m\^2 of carmustine (substituted if lomustine is not available) capsule on Day 1 of each cycle across dose level -1, 1, 2, 2a, and 3 in a 42-day cycle for all cycles.

Participants with rGBM uMGMT or mMGMT will receive 110 mg/m\^2 of lomustine or 200 mg/m\^2 of Carmustine (substituted if lomustine is not available) capsule on Day 1 of each cycle in a 42-day cycle for all cycles.

Participants with rGBM will receive 60-80 mg of selinexor oral tablet QW across dose level -1, 1 and 10 mg/kg of Bevacizumab intravenous (IV) infusion every 2 weeks (Q2W) in 28-day cycle for all cycles.

Participants with rGBM will receive 60-80 mg of selinexor oral tablet QW across dose level -1, 1 and will receive scalp application of 200 kilohertz (kHz) of transducer array ≥18 hours/day daily for each cycle in 28 day cycle for all cycles.

Dose and Formulation: 20 milligram (mg); Tablet Route of Administration: Oral

Selinexor

Dose strength and Formulation: 5, 20, 100, 140, 180, or 250 mg; Capsule Route of Administration: Oral

Temozolomide (TMZ)

Dose and Formulation: 10, 40, or 100 mg; Capsule Route of Administration: Oral

Lomustine (CCNU)

Radiation Therapy Oncology Group (RTOG) or European Organisation for Research and Treatment of Cancer (EORTC) methodologies of approximately 60 Gy in 30 fractions.

Standard Fractionated Radiation therapy (RT)

Dose and Formulation: 10 mg/kg; Route of Administration: Intravenous

Dose and Formulation: 200 kHz ≥18h/day; Route of administration: Scalp application of transducer arrays.

TTField

Dose and Formulation: 150 or 200 mg/m\^2; Route of Administration: Intravenous

Andrew B Lassman, MD

This is a Phase 1/2 study of selinexor in combination with standard of care (SoC) therapy for newly diagnosed glioblastoma (nGBM) or recurrent glioblastoma (rGBM). This study will be conducted in 2 phases: a Phase 1a dose finding study followed by Phase 1b (dose expansion) and a Phase 2 randomized efficacy exploration study and will independently evaluate 3 different combination regimens in 3 treatment arms in patients with nGBM (Arms A and B) or with rGBM (Arm C).

* Arm A: evaluating the combination of selinexor with radiation therapy (S-RT) in nGBM participants with uMGMT
* Arm B: evaluating the combination of selinexor with radiation therapy and temozolomide (TMZ) (S-TRT) in nGBM participants with methylated-O6-methylguanine-DNA-methyltransferase (mMGMT)
* Arm C: evaluating the combination of selinexor with lomustine (or carmustine, if lomustine is not available) (S-L/C) in rGBM participants regardless of MGMT status
* Arm D: evaluating the combination of selinexor with bevacizumab in rGBM participants regardless of MGMT status
* Arm E: evaluating the combination of selinexor with tumor treating fields (TTField) in rGBM participants regardless of MGMT status

A Study of Selinexor in Combination With Standard of Care Therapy for Newly Diagnosed or Recurrent Glioblastoma

A Phase 1/2 Study of Selinexor in Combination With Standard of Care (SoC) Therapy for Newly Diagnosed or Recurrent Glioblastoma

Karyopharm Therapeutics Inc

Amino Acids

Lapatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients will be treated with a pulse dose of lapatinib every week and temozolomide 75 mg/m2 daily during radiation. Lapatinib will be administered beginning on the first day of radiation and temozolomide (+/-2 days). External beam fractionated regional radiation will be given on consecutive week days at 200 cGy daily doses to a total dose of 6000 cGy. Patients will have rest from temozolomide only for 2-4 weeks. Patients will continue with weekly pulse-dosing of lapatinib. After a 2-4 weeks rest(for temozolomide only) following completion of radiation therapy, temozolomide will be restarted as Cycle 1 at 150 mg/m2/day for 5 days out of every 28.Subsequent cycles can increase to 200 mg/m2/day as tolerated per investigator's judgment. Lapatinib pulse doses will be continued every week without interruption.Treatment will continue for 24 additional 28-day cycles of temozolomide if there is no evidence of progression.

Lapatinib/Temozolomide/radiation

Pioanh Nghiemphu, M D

The purpose of this study is to test the safety and effects of a combination of a study drug, Lapatinib, plus the administration of standard radiation therapy and an FDA approved drug Temozolomide (chemotherapy agent) in patients with newly diagnozed glioblastoma Multiforme.Currently, only radiation therapy and Temozolomide chemotherapy are standard treatment for brain cancer.Lapatinib has not been FDA approved for use in brain tumors treatment. It has been approved to be used as a daily treatment with other chemotherapies by the FDA for the treatment of advanced breast cancer.

The purpose of this study is to find the answers to the following research questions:

1. Is Lapatinib given twice a week at higher dosages, with radiation therapy and Temozolomide, safe when given to patients with brain tumor?
2. What are the side effects of Lapatinib given twice a week at higher dosages when given with radiation therapy and Temozolomide and how often do they occur?
3. Can Lapatinib, radiation, and Temozolomide be effective in shrinking tumors when given to patients with brain tumors?
4. To determine whether the presence of genetic alterations specific proteins in the tumor samples can predict whether this study drug is effective on the tumor.

Lapatinib With Temozolomide and Regional Radiation Therapy for Patients With Newly-Diagnosed Glioblastoma Multiforme

Phase II Trial of Pulse Dosing of Lapatinib in Combination With Temozolomide and Regional Radiation Therapy for Upfront Treatment of Patients With Newly-Diagnosed Glioblastoma Multiforme

The primary objective is to estimate the overall survival in subjects with newly-diagnosed glioblastoma treated with lapatinib/temozolomide/radiation followed by lapatinib/temozolomide for 2 years or until progression is detected. If no progression is seen at 2 years, then single-agent lapatinib will be continued until progression.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of Selinexor in Combination With Standard of Care Therapy for Newly Diagnosed or Recurrent Glioblastoma	NCT04421378	Glioblastoma Mu...	Selinexor Temozolomide (T... Lomustine (CCNU... Standard Fracti... Bevacizumab TTField Carmustine	18 Years -	Karyopharm Therapeutics Inc
Lapatinib With Temozolomide and Regional Radiation Therapy for Patients With Newly-Diagnosed Glioblastoma Multiforme	NCT01591577	Newly Diagnosed...	Lapatinib/Temoz...	18 Years -	Jonsson Comprehensive Cancer Center

Spots Global Cancer Trial Database for newly diagnosed glioblastoma multiforme