Selinexor + Radiation for Brain Cancer

Recruiting at 127 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational drugs, Anti-cancer agents

Disqualifiers: Uncontrolled infection, Organ transplant, others

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

Compensation: Varies

Number of Visits: 6

210 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently receiving another investigational drug or other anti-cancer agents. It's best to discuss your current medications with the trial team.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently receiving other anti-cancer agents or investigational drugs.

What data supports the idea that Selinexor + Radiation for Brain Cancer is an effective treatment?

The available research shows that Selinexor, when used alone, has shown some effectiveness in treating recurrent glioblastoma, a type of brain cancer. In a study, Selinexor was found to penetrate tumors and had some positive effects, although it was not combined with radiation in this research. Additionally, Selinexor has shown antitumor activity in various solid tumors, suggesting it could be beneficial when combined with radiation for brain cancer. However, specific data on the combination of Selinexor and radiation for brain cancer is not provided in the available research, so more studies are needed to confirm its effectiveness. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Selinexor in treating brain cancer?

Research shows that Selinexor, a drug that blocks a protein involved in cancer cell growth, has shown effectiveness in various solid tumors, including glioblastoma, a type of brain cancer. In studies, it demonstrated antitumor activity and was generally safe, with some patients experiencing stable disease for several months. ^{1 2 3 4 5}

What safety data exists for Selinexor and radiation therapy for brain cancer?

The provided research does not directly address the safety data for the combination of Selinexor and radiation therapy for brain cancer. However, it includes studies on the safety and toxicity of various forms of radiation therapy, such as proton radiotherapy and image-guided proton irradiation, in different contexts. These studies highlight concerns about radiation-induced toxicities, especially in sensitive areas like the brain, and suggest that proton therapy may help minimize toxicity. No specific safety data for Selinexor in combination with radiation therapy for brain cancer is mentioned. ^{6 7 8 9 10}

Is the combination of Selinexor and radiation therapy generally safe for humans?

Radiation therapy, including techniques like intensity-modulated radiation therapy (IMRT) and proton radiotherapy, has been studied for various cancers and can reduce damage to normal tissues, but it may still cause significant side effects. Selinexor, also known as Xpovio, is a medication used in cancer treatment, but specific safety data for its combination with radiation therapy in brain cancer is not provided in the available research. ^{6 7 8 11 12}

Is the treatment Selinexor + Radiation Therapy promising for brain cancer?

Yes, Selinexor combined with Radiation Therapy is promising for brain cancer. Radiation Therapy, including advanced forms like Stereotactic Radiotherapy (SRT), is effective in targeting brain tumors while sparing healthy tissue. Selinexor, known by various names, is a drug that may enhance the effects of radiation, potentially improving treatment outcomes. ^{13 14 15 16 17}

What makes the Selinexor + Radiation treatment unique for brain cancer?

Selinexor combined with radiation therapy is unique because Selinexor is a drug that inhibits the export of tumor-suppressing proteins from the cell nucleus, potentially enhancing the effectiveness of radiation therapy in targeting brain cancer cells. This combination aims to improve treatment outcomes by making cancer cells more sensitive to radiation. ^{13 14 15 16 17}

Research Team

Adam L. Green

Principal Investigator

Children's Oncology Group

Eligibility Criteria

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.

Inclusion Criteria

I am not breastfeeding or have agreed to stop while on the trial.

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

Serum lipase =< 1.5 x ULN

Exclusion Criteria

Patients who have received a prior solid organ transplantation

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

I have macular degeneration, uncontrolled glaucoma, or cataracts.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

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 orally on specified days.

5-7 weeks

5 visits per week (in-person)

Maintenance

Patients receive selinexor orally on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Up to 24 cycles (28 days each)

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 3 months for the first year, every 6 months for years 2-3, and annually for years 4-5.

Up to 5 years

Regular follow-up visits

Treatment Details

Interventions

• Radiation Therapy
• Selinexor

Trial Overview 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).

Participant Groups

Group I: Treatment (selinexor and radiation therapy) Experimental Treatment 4 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.

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+

Findings from Research

Selinexor, an oral medication targeting exportin-1, showed a 6-month progression-free survival rate of up to 17% in patients with recurrent glioblastoma, indicating its potential efficacy as a monotherapy.

The treatment was generally manageable with side effects like fatigue and nausea, and at the highest dose of 80 mg weekly, it led to measurable tumor reductions in 28% of patients, with one complete response observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of the Efficacy and Safety of Oral Selinexor in Recurrent Glioblastoma. Lassman, AB., Wen, PY., van den Bent, MJ., et al.[2023]

Selinexor, an oral inhibitor of exportin 1 (XPO1), was found to be safe for patients with advanced solid tumors, with the most common side effects being mild to moderate fatigue, nausea, and anorexia, while serious toxicities were rare.

In a study of 189 patients, selinexor demonstrated some antitumor activity, with 4% of patients achieving a complete or partial response and 17% maintaining stable disease for at least 4 months, indicating its potential as a therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Class, First-in-Human Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Patients With Advanced Solid Tumors. Abdul Razak, AR., Mau-Soerensen, M., Gabrail, NY., et al.[2022]

In a phase Ib study involving 13 patients with advanced solid tumors, the combination of selinexor and carboplatin/paclitaxel showed some clinical activity, with 3 patients achieving unconfirmed partial responses and 5 patients having stable disease.

The most common treatment-related adverse events were severe blood-related issues, such as neutropenia and leukopenia, affecting 85% of patients, indicating that while the combination therapy has potential, it also carries significant risks that need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor in combination with carboplatin and paclitaxel in patients with advanced solid tumors: Results of a single-center, multi-arm phase Ib study. Thein, KZ., Karp, DD., Tsimberidou, A., et al.[2022]

In a phase 1b study involving 35 patients with recurrent solid tumors, the combination of oral selinexor and weekly paclitaxel was found to have a maximum tolerated dose of 60 mg, which was well-tolerated with no dose-limiting toxicities reported.

Among patients with ovarian cancer, the treatment showed a 17% response rate and a clinical benefit rate of 58%, with a median progression-free survival of 6.8 months, indicating promising efficacy and manageable toxicity for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor in combination with weekly paclitaxel in patients with metastatic solid tumors: Results of an open label, single-center, multi-arm phase 1b study with expansion phase in ovarian cancer. Westin, SN., Fu, S., Tsimberidou, A., et al.[2023]

Selinexor (KPT-330) is a first-in-class selective inhibitor of nuclear export that targets the protein exportin-1 (CRM1/XPO1), which is overexpressed in many tumor types and plays a crucial role in regulating protein trafficking essential for cancer cell growth and survival.

Preclinical studies have shown that Selinexor exhibits significant antineoplastic activity against various human solid and hematologic cancers, highlighting its potential as a novel therapeutic intervention in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SINE (selective inhibitor of nuclear export)--translational science in a new class of anti-cancer agents. Gerecitano, J.[2023]

Proton radiotherapy (PRT) is a feasible option for reirradiating patients with recurrent non-small cell lung cancer (NSCLC), with 93% of the 57 patients completing their treatment, but it can lead to significant toxicity, with 42% experiencing grade 3 or higher adverse effects.

The study found that higher doses to the esophagus and concurrent chemotherapy were linked to increased toxicity, and careful consideration of tumor characteristics is essential for optimizing patient outcomes in PRT for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-Institutional Prospective Study of Reirradiation with Proton Beam Radiotherapy for Locoregionally Recurrent Non-Small Cell Lung Cancer. Chao, HH., Berman, AT., Simone, CB., et al.[2022]

The study successfully established a method for image-guided proton irradiation in mouse brains, allowing for precise targeting and assessment of radiation effects, which is crucial for understanding potential adverse effects in normal tissues.

Using advanced imaging and Monte Carlo simulations, the research demonstrated a clear correlation between the proton dose distribution and DNA damage in the brain, highlighting the method's potential for translational studies in proton therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-precision image-guided proton irradiation of mouse brain sub-volumes. Suckert, T., Müller, J., Beyreuther, E., et al.[2021]

In a study involving 1,084 men undergoing three-dimensional conformal radiation therapy (3DCRT) for prostate cancer, the incidence of late gastrointestinal and genitourinary toxicity remained low, with rates ranging from 3% to 12% across different dose levels.

Higher doses of radiation (78 Gy at 2 Gy/fraction) were associated with significantly increased risks of grade 2 or greater toxicity compared to lower doses (68.4 Gy to 79.2 Gy at 1.8 Gy/fraction), indicating that while 3DCRT is generally well-tolerated, careful consideration of dose is crucial for minimizing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term toxicity following 3D conformal radiation therapy for prostate cancer from the RTOG 9406 phase I/II dose escalation study. Michalski, JM., Bae, K., Roach, M., et al.[2022]

In a retrospective analysis of three patients who experienced treatment-related toxicities after intracranial proton therapy, it was found that the relative biological effectiveness (RBE) in the areas of toxicity was significantly higher than expected, leading to increased radiation doses and normal tissue complication probabilities (NTCP).

Multi-field optimized (MFO) treatment plans were developed that successfully reduced the dose-averaged linear energy transfer (LETd), RBE-weighted dose (DRBE), and NTCP in critical organs at risk, suggesting that these strategies could minimize toxicity without compromising the effectiveness of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spatial correlation of linear energy transfer and relative biological effectiveness with suspected treatment-related toxicities following proton therapy for intracranial tumors. Ödén, J., Toma-Dasu, I., Witt Nyström, P., et al.[2020]

Radiotherapy (RT) for spinal ependymoma, particularly in patients with adverse features like incomplete resection or disseminated disease, resulted in a 5-year overall survival rate of 83.7% and a progression-free survival rate of 70.8% based on a study of 25 patients.

Patients with grade I ependymoma had significantly better survival outcomes compared to those with grade II/III, indicating that tumor grade is an important factor in predicting the effectiveness of RT, while the treatment was generally safe with minimal late toxicities observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of radiotherapy for spinal cord ependymoma with adverse prognostic features: a single-center study. Byun, HK., Yi, S., Yoon, HI., et al.[2019]

In a study of 192 patients with localized prostate cancer, using prostate-based IGRT (P-IGRT) resulted in significantly lower acute gastrointestinal toxicities compared to bony structure-based IGRT (B-IGRT), with rates of 3% versus 11%.

Both P-IGRT and B-IGRT showed similar prostate-specific antigen failure-free survival rates at 3 years (95.5% for P-IGRT and 92.7% for B-IGRT), indicating that P-IGRT can reduce toxicity without compromising tumor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreased acute toxicities of intensity-modulated radiation therapy for localized prostate cancer with prostate-based versus bone-based image guidance. Nakamura, K., Mizowaki, T., Inokuchi, H., et al.[2018]

Motexafin gadolinium (Xcytrin) is a promising radiosensitizer that enhances the effectiveness of radiation therapy for brain tumors, potentially improving treatment outcomes for patients with brain metastases and primary brain tumors.

This agent is well tolerated by patients and shows tumor-specific uptake, suggesting it could be a valuable addition to current treatment strategies in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motexafin gadolinium: a novel radiosensitizer for brain tumors. Forouzannia, A., Richards, GM., Khuntia, D., et al.[2014]

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]

In a study involving 18 patients with early-stage central lung tumors, online adaptive intensity modulated proton therapy (IMPT) significantly reduced the mean dose to the bronchial tree compared to MR-guided radiotherapy (MRgRT), suggesting a safer treatment option with lower toxicity risks.

Both non-adaptive and online adaptive IMPT showed significant reductions in the mean doses to the ipsilateral lung and heart compared to MRgRT, indicating improved dose sparing for organs-at-risk during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of MR-guided radiotherapy accumulated doses for central lung tumors with non-adaptive and online adaptive proton therapy. Rabe, M., Palacios, MA., van Sörnsen de Koste, JR., et al.[2023]

Stereotactic radiotherapy (SRT) is an effective treatment for brain metastases, showing a median survival time of 12.9 months and a 1-year overall survival rate of 53.9% based on a study of 78 patients with 122 intracranial lesions.

Combining SRT with whole brain radiotherapy (WBRT) can further improve survival, particularly in patients with controlled extracranial lesions or multiple intracranial lesions, highlighting the importance of patient condition in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of X-ray stereotactic radiotherapy on brain metastases and prognostic analysis. Wei, W., Deng, ML., Wu, SX., et al.[2019]

Motexafin gadolinium (MGd) is a novel radiation sensitizer that may improve the effectiveness of whole brain radiation therapy (WBRT) for patients with brain metastases from non-small cell lung cancer (NSCLC).

Current outcomes for NSCLC patients undergoing WBRT are poor, with median survival times only in months, highlighting the need for effective treatments like MGd to enhance therapeutic results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motexafin gadolinium injection for the treatment of brain metastases in patients with non-small cell lung cancer. Thomas, SR., Khuntia, D.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

A Phase II Study of the Efficacy and Safety of Oral Selinexor in Recurrent Glioblastoma. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

First-in-Class, First-in-Human Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Patients With Advanced Solid Tumors. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Selinexor in combination with carboplatin and paclitaxel in patients with advanced solid tumors: Results of a single-center, multi-arm phase Ib study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Selinexor in combination with weekly paclitaxel in patients with metastatic solid tumors: Results of an open label, single-center, multi-arm phase 1b study with expansion phase in ovarian cancer. [2023]

5. England pubmed.ncbi.nlm.nih.gov

SINE (selective inhibitor of nuclear export)--translational science in a new class of anti-cancer agents. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Multi-Institutional Prospective Study of Reirradiation with Proton Beam Radiotherapy for Locoregionally Recurrent Non-Small Cell Lung Cancer. [2022]

7. Ireland pubmed.ncbi.nlm.nih.gov

High-precision image-guided proton irradiation of mouse brain sub-volumes. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Long-term toxicity following 3D conformal radiation therapy for prostate cancer from the RTOG 9406 phase I/II dose escalation study. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Spatial correlation of linear energy transfer and relative biological effectiveness with suspected treatment-related toxicities following proton therapy for intracranial tumors. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Clinical outcomes of radiotherapy for spinal cord ependymoma with adverse prognostic features: a single-center study. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Intensity modulated radiation therapy and proton radiotherapy for non-small cell lung cancer. [2019]

12. Japan pubmed.ncbi.nlm.nih.gov

Decreased acute toxicities of intensity-modulated radiation therapy for localized prostate cancer with prostate-based versus bone-based image guidance. [2018]

13. England pubmed.ncbi.nlm.nih.gov

Motexafin gadolinium: a novel radiosensitizer for brain tumors. [2014]

14. China 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. [2022]

15. United States pubmed.ncbi.nlm.nih.gov

Comparison of MR-guided radiotherapy accumulated doses for central lung tumors with non-adaptive and online adaptive proton therapy. [2023]

16. England pubmed.ncbi.nlm.nih.gov

Efficacy of X-ray stereotactic radiotherapy on brain metastases and prognostic analysis. [2019]

17. New Zealand pubmed.ncbi.nlm.nih.gov

Motexafin gadolinium injection for the treatment of brain metastases in patients with non-small cell lung cancer. [2019]