A Phase 1 and Randomized Phase 2 Trial of Selinexor and Temozolomide in Recurrent Glioblastoma
National Cancer Institute (NCI)
Summary
This phase I/II trial tests the safety, side effects and best dose of selinexor given in combination with the usual chemotherapy (temozolomide) and compares the effect of this combination therapy versus the usual chemotherapy alone (temozolomide) in treating patients with glioblastoma that has come back (recurrent). Selinexor is in a class of medications called selective inhibitors of nuclear export (SINE). It works by blocking a protein called CRM1, which may keep cancer cells from growing and may kill them. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid and may kill tumor cells and slow down or stop tumor growth. Giving selinexor in combination with usual chemotherapy (temozolomide) may shrink or stabilize the tumor better than the usual chemotherapy with temozolomide alone in patients with recurrent glioblastoma.
Description
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose of temozolomide followed by selinexor in recurrent glioblastoma patients as determined by dose-limiting toxicities (DLTs) and the total toxicity profile. (Phase I) II. To evaluate the efficacy of sequentially administering temozolomide and selinexor in recurrent glioblastoma as determined by progression-free survival (PFS). (Phase II) SECONDARY OBJECTIVES: I. To evaluate overall response rate as determined by Response Assessment in Neuro-Oncology (RANO) response criteria. II. To evaluate the efficacy of sequentially administeri…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Patients must have histologically confirmed glioblastoma (IDH wild-type, MGMT promoter methylated) that has undergone resection or biopsy upon first recurrence. Recurrence at site of prior involvement is defined by histopathological evidence of viable neoplastic cells associated with any of the following: mitotic activity, increased proliferation rate, micro-endothelial proliferation, or pseudo-palisading necrosis * Prior to resection or biopsy, patients must have measurable disease, defined as at least one bi-dimensional contrast-enhancing lesion with clearly defined ma…
Interventions
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- DrugPlacebo Administration
Given PO
- DrugSelinexor
Given PO
- DrugTemozolomide
Given PO
Locations (36)
- Mayo Clinic Hospital in ArizonaPhoenix, Arizona
- City of Hope Comprehensive Cancer CenterDuarte, California
- UC San Diego Moores Cancer CenterLa Jolla, California
- Keck Medicine of USC KoreatownLos Angeles, California
- Los Angeles General Medical CenterLos Angeles, California
- USC / Norris Comprehensive Cancer CenterLos Angeles, California