What side effects are associated with this type of intervention?

Selinexor, a selective inhibitor of nuclear export, can cause side effects such as nausea, fatigue, thrombocytopenia (low platelet count), and hyponatremia (low sodium levels). Radiation therapy, which uses high energy to kill tumor cells, can lead to side effects including fatigue, skin changes, hair loss, and potential long-term effects such as cognitive decline and radiation necrosis. Combining these treatments may result in a cumulative effect of these side effects, requiring careful management and monitoring.

What prior FDA approvals exist?

As of now, there are no FDA-approved treatments specifically for Diffuse Intrinsic Pontine Glioma (DIPG) that combine a selective inhibitor of nuclear export like Selinexor with Radiation Therapy. Radiation Therapy remains the standard treatment for DIPG, as it can help shrink tumors and alleviate symptoms, but it is not curative. Research and clinical trials are ongoing to find more effective treatments, including the combination of novel agents like Selinexor with Radiation Therapy.

What other types of research exist?

Promising novel alternatives for DIPG patients include: 1) Bevacizumab (BEV) combined with Temozolomide (TMZ) or Irinotecan (CPT), which has shown similar efficacy to BEV alone with good tolerance in recurrent glioblastoma patients. 2) Cilengitide, an integrin-targeting peptide, which has shown antitumor benefits and minimal toxicity in clinical trials for glioblastoma. 3) Immunotherapy approaches, such as PD-1 blockade with nivolumab, which has shown activity in recurrent high-grade meningiomas and could be explored for DIPG.

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Selinexor + Radiation for Brain Cancer

Phase 1 & 2

Recruiting

Led By Adam L Green

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 a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2

Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 (within 7 days prior to step 1 enrollment)

Must not have

Patients must not have received any prior therapy for their central nervous system (CNS) malignancy except for surgery and steroid medications

Patients with known macular degeneration, uncontrolled glaucoma, or cataracts

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests the safety and effectiveness of combining selinexor with radiation therapy in children and young adults with aggressive brain tumors. Selinexor is a drug that blocks a protein to stop cancer cells from growing. The study aims to find the best dose and see if this combination can shrink tumors.

Who is the study for?

This trial is for children and young adults aged 1 to 21 with newly-diagnosed DIPG or HGG that have a specific genetic mutation (H3 K27M). They must be able to breathe without difficulty, not pregnant or breastfeeding, willing to use birth control if applicable, and have not received prior cancer treatment except surgery. Patients should also have normal organ function.

What is being tested?

The trial is testing the safety and effectiveness of Selinexor combined with standard radiation therapy on brain tumors in two phases: finding the highest dose patients can take without severe side effects (Part 1), then seeing how well this dose works against the tumors (Part 2).

What are the potential side effects?

Selinexor may cause fatigue, nausea, loss of appetite, blood count changes, and other symptoms related to its effect on protein blocking in cancer cells. Radiation therapy might lead to skin irritation at the treated site, tiredness, headaches depending on where it's applied.

Eligibility Criteria

Inclusion Criteria

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

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I can take care of myself but might not be able to do heavy physical work.

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My kidney function, measured by creatinine clearance or GFR, is good.

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I am a woman able to have children and have a negative pregnancy test.

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I am between 12 and 21 years old.

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I have been recently diagnosed with a specific type of brain tumor.

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My bilirubin levels are within the normal range for my age.

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I am not pregnant.

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I am newly diagnosed with a high-grade glioma or have DIPG.

Exclusion Criteria

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

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I have only had surgery and steroids for my brain cancer.

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I have macular degeneration, uncontrolled glaucoma, or cataracts.

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I am 18 or older with a specific type of brain tumor that is not H3 K27M-mutant.

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I do not have cancer that has spread to other parts of my body.

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I cannot undergo the specific radiation therapy outlined in the study.

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I do not have any infections that are currently uncontrolled.

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I have a movement disorder that is moderate to severe.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 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

Event free survival (EFS)

Maximum tolerated dose

Overall Survival (OS)

+1 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (selinexor and radiation therapy)Experimental Treatment4 Interventions

CHEMORADIOTHERAPY: Patients receive standard of care radiation therapy 5 days per week for 5-7 weeks. Starting on day 4 or 5 of radiation therapy, patients receive selinexor PO on 1, 8, 15, 22, 29, 36, 43, and 50 in the absence of disease progression or unacceptable toxicity. After a 2-week rest period, patients proceed to Maintenance. Patients undergo a MRI and may undergo a biopsy during screening. MAINTENANCE: Patients receive selinexor PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for up to 24 cycles of maintenance therapy in the absence of disease progression or unacceptable toxicity. Patients undergo a MRI on study and during follow-up.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biopsy

2014

Completed Phase 4

~1090

Magnetic Resonance Imaging

2017

Completed Phase 3

~1160

Radiation Therapy

2017

Completed Phase 3

~7250

Selinexor

2020

Completed Phase 3

~1730

0 / 15Eligibility 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

The most common treatments for Diffuse Intrinsic Pontine Glioma (DIPG) include selinexor and radiation therapy. Selinexor works by inhibiting the CRM1 protein, which disrupts the export of tumor suppressor proteins from the nucleus, thereby preventing cancer cell growth and inducing cell death. Radiation therapy, on the other hand, uses high-energy radiation to directly kill tumor cells and shrink tumors. These mechanisms are crucial for DIPG patients because this type of glioma is highly aggressive and located in a critical area of the brain, making it difficult to treat. By combining selinexor's ability to inhibit cancer cell growth with radiation's tumor-killing effects, there is potential for improved treatment efficacy and patient outcomes.

A Phase II Study of the Efficacy and Safety of Oral Selinexor in Recurrent Glioblastoma.How did lomustine become standard of care in recurrent glioblastoma?The XPO1 Inhibitor Selinexor Inhibits Translation and Enhances the Radiosensitivity of Glioblastoma Cells Grown In Vitro and In Vivo.