Recurrent glioblastoma or other brain cancer after failure of radiation therapy and temozolomide MedDRA version: 20.0 Level: PT Classification code 10002224 Term: Anaplastic astrocytoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10073128 Term: Anaplastic oligodendroglioma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20
Conditions
Sponsors
Karyopharm Therapeutic, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Pathologically confirmed diagnosis of GBM (including all histologic variants) with radiographic evidence of recurrent disease after treatment with radiotherapy and temozolomide; 2. Age = 18 years; 3. Karnofsky Performance Status (KPS) = 60; 4. Patients enrolling in the medical arm (Arms B, C, or D) must be on a stable or decreasing dose of corticosteroids (or none) for at least 5 days prior to the baseline CT/MRI; 5. Patients must have received prior treatment with radiation therapy and temozolomide (all arms); 6. Measurable disease (according to RANO guidelines, within 14 days of starting treatment). Measurable disease after surgery on arm A is not required. 7. Written informed consent obtained prior to any screening procedures. Patients must be willing and able to comply with the protocol and aware of the investigational nature of this study. 8. Patients must have adequate bone marrow function and organ function within 2 weeks of study treatment as defined by the following laboratory criteria; o Hematopoietic function: total white blood cell count (WBC) = 3000/mm³, absolute neutrophil count (ANC) = 1500/mm³, platelet count = 125,000/mm³; hemoglobin = 9g/dL o Hepatic function: bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Patients must not have significant medical illness that in the Investigator’s opinion cannot be adequately controlled with appropriate therapy or would compromise the patient’s ability to tolerate this therapy. 2. <24 days from prior temozolomide, <6 weeks from nitrosourea, <4 weeks from other chemotherapy or investigational agents prior to start of treatment within study. 3. Unstable cardiovascular function. 4. Known active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen); hepatitis testing is not required. 5. Known HIV infection; HIV testing is not required. 6. Markedly decreased visual acuity if attributed to other causes than GBM. 7. Active infection requiring parenteral systemic antibiotics. 8. Patients with coagulation problems and medically significant bleeding in the month prior to start of treatment (e.g., peptic ulcer, epistaxis, spontaneous bleeding). Prior history of DVT or PE is not exclusionary. 9. Patients who are pregnant or breast-feeding. 10. Other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off all therapy for that disease for a minimum of 3 years. 11. Patients must not have significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea or inability to swallow oral medications. 12. Dehydration of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade = 1. 13. Patients must not have serious psychiatric or medical conditions that could interfere with treatment. 14. History of organ allograft. 15. Concurrent therapy with approved or investigational anticancer therapeutics. 16. Prior treatment with bevacizumab or other direct VEGF/ VEGFR inhibitors. For any question of the definition of a direct VEGF/VEGFR consult Sponsor. 17. Arms C and D only: Body Surface area < 1.2 m2, to avoid a dose exceeding the maximum allowable dose of 70 mg/m2. 18. Major surgery < 4 weeks prior to the start of study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of Selinexor in adults with recurrent GBM as determined by the 6-months progression-free survival (6mPFS) rate;Secondary Objective: • To determine the efficacy of Selinexor in adults with recurrent GBM as determined by response rate according to the RANO criteria • To determine the efficacy of Selinexor in adults with recurrent GBM as estimated by median overall survival (OS) • To determine the efficacy of Selinexor in adults with recurrent GBM as determined by median progression-free survival (PFS) • To evaluate safety and tolerability of Selinexor • To determine tumor concentration of Selinexor and molecular effects during treatment • To evaluate preliminary evidence of efficacy of Selinexor in a small group of patients undergoing cytoreductive surgery (Arm A);Primary end point(s): • 6-months Progression-free survival (6mPFS) rate (Progression of disease defined according to the RANO criteria);Timepoint(s) of evaluation of this end point: 6 months after start of treatment within the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 Response rate according to the RANO criteria 2 Median progression-free survival (PFS) 3 Median overall survival (OS) 4 Safety 5 Tumor concentration of Selinexor;Timepoint(s) of evaluation of this end point: 1. Assessment of disease status every 8 weeks from start of therapy within study 2. From Start of therapy within study to occurrence of disease progression 3. At the time of death of patients 4. From Start of therapy within study to End of treatment visit 5. At the time of surgery in Arm A (Day 3 or 8) | — |
Countries
Denmark, Netherlands, United States
Contacts
Public ContactClinical Trials Information
Karyopharm Therapeutic, Inc.
Outcome results
None listed