What is the mechanism of action of this treatment?

Common treatments for Glioblastoma include Selinexor, which blocks the CRM1 protein to prevent the export of tumor suppressor proteins from the nucleus, promoting cancer cell death. Temozolomide, an alkylating agent, damages the DNA of cancer cells, leading to their death. Bevacizumab, an angiogenesis inhibitor, blocks the growth of new blood vessels to the tumor, starving it of nutrients. These treatments are crucial as they target the cancer cells' growth, division, and sustenance, potentially improving survival and quality of life for Glioblastoma patients.

What side effects are associated with this type of intervention?

Common treatments for glioblastoma include temozolomide, an alkylating agent, and newer agents like Selinexor, a selective inhibitor of nuclear export. Temozolomide is known to cause side effects such as nausea, vomiting, fatigue, and myelosuppression, which can lead to increased risk of infection and anemia. Selinexor, which blocks the CRM1 protein, may cause side effects including nausea, fatigue, anorexia, and thrombocytopenia. Both treatments can also potentially impact cognitive function and reproductive health.

What prior FDA approvals exist?

The FDA has approved several treatments for glioblastoma, including temozolomide, an alkylating agent that damages the DNA of tumor cells. While Selinexor, a Selective Inhibitor of Nuclear Export (SINE) that blocks the CRM1 protein, is currently being studied, there are no other FDA-approved drugs with a similar mechanism of action for glioblastoma. Temozolomide remains a cornerstone of glioblastoma treatment, often used in combination with other therapies to enhance its efficacy.

What other types of research exist?

Promising novel alternatives to Selinexor for Glioblastoma patients include: 1) Ivosidenib, a mutant-IDH1 inhibitor, which has shown tolerability and some efficacy in clinical trials for IDH1-mutant gliomas. 2) Vorasidenib, a dual mutant-IDH1/2 inhibitor, currently in phase III testing for IDH1/2-mutant gliomas. 3) Vismodegib, a Smoothened (SMO) inhibitor, which has shown activity in SHH medulloblastomas and is being explored for Glioblastoma. These alternatives target different pathways and mechanisms, offering potential new avenues for treatment.

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Selective Inhibitor of Nuclear Export

Selinexor + Temozolomide for Recurrent Glioblastoma

Phase 1 & 2

Recruiting

Led By Frances E Chow

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have received first-line treatment of temozolomide plus radiotherapy

Age >= 18 years

Must not have

Patients must have full recovery of organ and marrow function following chemotherapy

Hospitalized patients with severe COVID-19

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests selinexor with temozolomide for patients whose brain cancer has returned. Selinexor blocks a protein that helps cancer cells grow, and temozolomide damages their DNA to kill them or stop their growth. Temozolomide is a DNA methylating drug currently used as a first-line treatment in glioblastoma therapy.

Who is the study for?

Adults with recurrent glioblastoma who've had prior temozolomide and radiotherapy can join. They must have measurable disease, adequate organ function, and a Karnofsky performance status of at least 60%. HIV-positive patients on effective therapy, those cured of hepatitis C, or with controlled hepatitis B are eligible. Pregnant women and breastfeeding mothers cannot participate; others must use contraception.

What is being tested?

The trial is testing the safety and effectiveness of adding Selinexor to standard chemotherapy (Temozolomide) for recurrent brain tumors. It's assessing if this combination better controls tumor growth compared to Temozolomide alone.

What are the potential side effects?

Selinexor may cause fatigue, nausea, loss of appetite, blood count changes, and other organ-related side effects. Temozolomide can lead to similar issues including headaches, constipation or diarrhea, dizziness, and potential hair loss.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have received temozolomide and radiotherapy as my first treatment.

Select...

I am 18 years old or older.

Select...

My kidney function is normal or only mildly reduced.

Select...

I have chronic hepatitis B but it's under control with medication.

Select...

My heart condition does not severely limit my physical activity.

Select...

My glioblastoma was confirmed with a biopsy and has specific genetic features.

Select...

I had hepatitis C but am now cured or have no detectable virus while on treatment.

Select...

I have only had surgery or a biopsy for my recurring disease, no other treatments.

Select...

I can care for myself but may not be able to do active work.

Select...

My cancer can be measured by tests before any surgery or biopsy.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

My organs and bone marrow have fully recovered from chemotherapy.

Select...

I am hospitalized with severe COVID-19.

Select...

I am allergic to medications similar to selinexor or temozolomide.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression-free survival (PFS) (Phase II)

Recommended phase 2 dose (RP2D) (Phase I)

Secondary study objectives

Median overall survival

Molecular signatures of vulnerability

Response according to response assessment in neuro-oncology criteria (RANO) criteria

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Group II (temozolomide, selinexor)Experimental Treatment4 Interventions

Patients receive temozolomide PO on days 1-5 of each cycle and selinexor PO on days 8 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo MRI throughout the study and blood sample collection while on study.

Group II: Group I (temozolomide)Active Control3 Interventions

Patients receive temozolomide PO on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo MRI throughout the study and blood sample collection while on study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Magnetic Resonance Imaging

2017

Completed Phase 3

~1180

Biospecimen Collection

2004

Completed Phase 3

~2030

Selinexor

2020

Completed Phase 3

~1730

Temozolomide

2010

Completed Phase 3

~1880

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Glioblastoma include Selinexor, which blocks the CRM1 protein to prevent the export of tumor suppressor proteins from the nucleus, promoting cancer cell death. Temozolomide, an alkylating agent, damages the DNA of cancer cells, leading to their death. Bevacizumab, an angiogenesis inhibitor, blocks the growth of new blood vessels to the tumor, starving it of nutrients. These treatments are crucial as they target the cancer cells' growth, division, and sustenance, potentially improving survival and quality of life for Glioblastoma patients.