Selinexor + Chemotherapy + Radiation for Brain Cancer

Overseen By Theresa Cooley Zgela, R.N.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must be taking: Temozolomide, Selinexor

Must not be taking: Investigational agents

Disqualifiers: Prior brain radiation, Chemotherapy, Severe liver dysfunction, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination treatment for glioblastoma, a challenging type of brain cancer. Researchers aim to determine the safe dosage of selinexor (a nuclear export inhibitor) when used with chemotherapy (temozolomide) and radiation therapy. This combination seeks to improve treatment outcomes. The trial seeks participants recently diagnosed with glioblastoma who have not yet received chemotherapy or radiation treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that selinexor, when combined with temozolomide and radiation, is under study for safety in treating brain cancer. Previous studies have explored the tolerance of selinexor with standard treatments like radiation and chemotherapy. The goal is to determine the highest dose that can be taken without serious side effects.

Some research indicates that selinexor can be safely combined with other cancer treatments, though side effects may occur. Common issues include nausea, fatigue, and low blood cell counts, which are important to monitor as they can impact overall health.

As this is an early-phase trial, it focuses on safety and dosage, so there is limited data on long-term safety or effectiveness. However, further testing of selinexor suggests confidence in its potential benefits and manageable risks from earlier studies. Participants in this trial will undergo regular check-ups and tests to ensure their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for brain cancer?

Researchers are excited about the combination of selinexor with temozolomide and radiation therapy for brain cancer because it introduces a new mechanism of action. Unlike the standard treatments, which often focus solely on killing cancer cells directly, selinexor works by blocking a protein that helps cancer cells survive, potentially enhancing the effectiveness of chemotherapy and radiation. This approach could make the cancer cells more sensitive to existing treatments, offering a fresh strategy in tackling brain cancer.

What evidence suggests that this trial's treatments could be effective for brain cancer?

Research has shown that selinexor, when combined with chemotherapy and radiation, might improve outcomes for glioblastoma patients. In this trial, participants will receive selinexor, temozolomide, and radiation therapy. Studies suggest that adding selinexor to standard treatment could shrink or stabilize brain tumors more effectively than chemotherapy alone. Ongoing trials are examining the safety and benefits of this combination for both new and recurrent glioblastoma cases. While radiation and temozolomide are standard treatments, selinexor may enhance their effects. Early results appear promising, but more data is needed to confirm its efficacy. ^{1 2 4 5 6}

Who Is on the Research Team?

Kevin A Camphausen, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults over 18 with newly diagnosed glioblastoma or gliosarcoma who haven't had chemo or radiation, can undergo radiotherapy and temozolomide treatment, have a certain level of physical function (KPS >70), and agree to use contraception. Excluded are those with uncontrolled infections, severe liver issues, pregnant/nursing women, HIV patients, prior brain RT or chemotherapy for glioma.

Inclusion Criteria

My diagnosis is glioblastoma or gliosarcoma (grade IV astrocytoma).

I am eligible for specific radiation therapy and temozolomide treatment.

Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment and for one month after treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

Exclusion Criteria

I do not have HIV due to potential treatment complications.

I can take oral medication without issues like vomiting or severe diarrhea.

I haven't had significant bleeding or coagulation issues in the last month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Radiation and Chemotherapy

Participants receive radiation therapy and temozolomide daily, with selinexor administered weekly

6 weeks

5 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

11 weeks

1 visit (in-person) at 1 month, then every 2 months for 2 years, then every 3 months for another year

What Are the Treatments Tested in This Trial?

Interventions

• Radiation Therapy
• Selinexor
• Temozolomide

Trial Overview The trial is testing the highest dose of Selinexor that's tolerable when combined with Temozolomide and generic Radiation Therapy in treating new cases of brain cancer. Participants will receive daily radiation for up to 6 weeks while taking oral Selinexor weekly and Temozolomide daily during this period.

How Is the Trial Designed?

Group I: 1/Experimental Therapy - Selinexor with Temozolomide and Radiation Experimental Treatment 7 Interventions

Selinexor with temozolomide and radiation

Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Combining brain radiotherapy (RT) with temozolomide (TMZ) significantly improves the objective response rate (ORR) in patients with brain metastases, with an odds ratio of 2.27, indicating a better response to treatment compared to RT alone.

However, this combination treatment does not lead to a significant improvement in overall survival (OS) or progression-free survival (PFS), and it is associated with increased adverse effects, such as severe nausea and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain Radiotherapy plus Concurrent Temozolomide versus Radiotherapy Alone for Patients with Brain Metastases: A Meta-Analysis. Zhao, Q., Qin, Q., Sun, J., et al.[2018]

Current treatments for brain tumors are often inadequate, leading to ongoing research into the use of concurrent chemotherapy and radiotherapy to improve patient outcomes.

Trials are exploring new agents that can effectively cross the blood-brain barrier and minimize overlapping toxicities, which may enhance the safety and efficacy of combined therapies for brain tumor patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemotherapy and radiotherapy in patients with brain tumors. Glantz, MJ., Kim, L., Choy, H., et al.[2005]

Temozolomide (TMZ) was found to effectively radiosensitize two out of three human glioblastoma multiforme (GBM) cell lines when combined with single-dose gamma-irradiation, indicating its potential to enhance the effectiveness of radiation therapy.

In a study involving three genetically characterized GBM cell lines, TMZ demonstrated an additive effect with fractionated irradiation, particularly showing a significant reduction in surviving cells in the AMC 3046 cell line, suggesting that TMZ can improve treatment outcomes for certain GBM patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential radiosensitizing potential of temozolomide in MGMT promoter methylated glioblastoma multiforme cell lines. van Nifterik, KA., van den Berg, J., Stalpers, LJ., et al.[2018]

In a randomized trial involving 20 patients with multiple brain metastases, stereotactic radiotherapy (SRT) was found to significantly preserve quality of life (QoL) compared to whole-brain radiotherapy (WBRT), particularly in mobility, self-care, and alopecia after 3 months.

Patients receiving SRT reported better physical and social functioning, indicating that SRT not only controls local tumors but also enhances the overall well-being of patients compared to traditional WBRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life among patients with 4 to 10 brain metastases after treatment with whole-brain radiotherapy vs. stereotactic radiotherapy: a phase III, randomized, Dutch multicenter trial. Hartgerink, D., Bruynzeel, A., Eekers, D., et al.[2022]

Combining CyberKnife stereotactic radiosurgery (SRS) with a dose-dense regimen of temozolomide (TMZ) significantly improved median survival (12 months vs. 7 months) and 6-month progression-free survival (66.7% vs. 18%) in patients with recurrent glioblastoma multiforme (GBM).

While the combination treatment showed better outcomes, over 40% of patients experienced grade 3 hematological toxicity, indicating a need for careful monitoring of side effects in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of CyberKnife re-irradiation and "dose dense" temozolomide for recurrent gliomas. Conti, A., Pontoriero, A., Arpa, D., et al.[2022]

In a study of 45 breast cancer patients undergoing stereotactic radiosurgery (SRS) for brain metastases, 22.2% developed clinically significant radionecrosis (CSRN), with a striking 39.1% of those receiving trastuzumab emtansine (T-DM1) experiencing this complication compared to only 4.5% of those not receiving T-DM1.

The use of T-DM1 was linked to a 13.5-fold increase in the risk of CSRN, likely due to its targeting of reactive astrocytes, which enhances radiation-induced damage and swelling, suggesting that caution is needed when combining T-DM1 with SRS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of Trastuzumab Emtansine and Stereotactic Radiosurgery Results in High Rates of Clinically Significant Radionecrosis and Dysregulation of Aquaporin-4. Stumpf, PK., Cittelly, DM., Robin, TP., et al.[2020]

In a study of 128 patients with high-grade gliomas, the combination of radiotherapy and temozolomide showed favorable outcomes, with only 9% experiencing grade 3 hematological toxicity and no grade 4 toxicity reported, indicating a manageable safety profile.

Statistical analysis revealed that factors such as age, tumor histology, and the use of temozolomide were linked to improved 2-year overall survival, supporting the efficacy of this treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide and radiotherapy as first-line treatment of high-grade gliomas. Corsa, P., Parisi, S., Raguso, A., et al.[2022]

In a study of 67 patients with newly diagnosed glioblastoma multiforme, the combination of temozolomide, thalidomide, and radiation therapy resulted in a median survival of 73 weeks, indicating a favorable outcome compared to those not receiving adjuvant chemotherapy.

The treatment was generally well tolerated, but the specific benefit of adding thalidomide to temozolomide remains uncertain, as the survival outcomes were similar to those seen with other chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of temozolomide and thalidomide with radiation therapy for newly diagnosed glioblastoma multiforme. Chang, SM., Lamborn, KR., Malec, M., et al.[2018]

Intensity-modulated radiotherapy (IMRT) effectively reduces radiation exposure to healthy tissues, minimizing side effects and enhancing treatment efficiency by allowing for smaller or more frequent doses.

Chemoradiotherapy, particularly using cisplatin and cetuximab, has become a standard treatment for tumors, especially in cases beyond early-stage disease, highlighting its role in improving cancer care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oncological treatment modalities in head and neck cancer]. Saarilahti, K., Lindholm, P.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8810630/

A Phase II Study of the Efficacy and Safety of Oral Selinexor in ... Ongoing trials are evaluating the safety and efficacy of selinexor in combination with other therapies for newly diagnosed and recurrent glioblastoma.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04216329

Study Details | NCT04216329 | Selinexor (KPT-330) in ... Although radiation has been shown to improve outcomes in patients with glioblastoma (GBM), median survival remains poor. Even with the addition of temozolomide ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.TPS2071

A phase 1/2 study of selinexor in combination with ... The current trial tests the hypothesis that the addition of selinexor to standard therapy will improve clinical outcomes for patient with ndGBM or rGBM.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05432804

NCT05432804 | Testing the Addition of an Anti-cancer ... Giving selinexor in combination with usual chemotherapy (temozolomide) may shrink or stabilize the tumor better than the usual chemotherapy with temozolomide ...

5. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04216329/

Clinical Trial: NCT04216329 Objective: To learn the highest dose of selinexor that people with brain cancer can tolerate when given with temozolomide and radiation therapy.

6. dana-farber.org dana-farber.org/clinical-trials/20-283

A Phase 1/2 Study of Selinexor in Combination with ... 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 ...