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.
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.12345
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.678910
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.1112131415
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
See 18 more
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.
See 8 more
Treatment Details
Interventions
- Radiation Therapy (Radiation)
- Selinexor (Selective Inhibitors of Nuclear Export)
Trial OverviewThe 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
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.
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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UCSF Benioff Children's Hospital OaklandOakland, CA
Children's National Medical CenterWashington, United States
Lucile Packard Children's Hospital Stanford UniversityPalo Alto, CA
University of Kentucky/Markey Cancer CenterLexington, KY
More Trial Locations
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
A Phase II Study of the Efficacy and Safety of Oral Selinexor in Recurrent Glioblastoma. [2023]Selinexor is an oral selective inhibitor of exportin-1 (XPO1) with efficacy in various solid and hematologic tumors. We assessed intratumoral penetration, safety, and efficacy of selinexor monotherapy for recurrent glioblastoma.
First-in-Class, First-in-Human Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Patients With Advanced Solid Tumors. [2022]Purpose This trial evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of selinexor (KPT-330), a novel, oral small-molecule inhibitor of exportin 1 (XPO1/CRM1), and determined the recommended phase II dose. Patients and Methods In total, 189 patients with advanced solid tumors received selinexor (3 to 85 mg/m2) in 21- or 28-day cycles. Pre- and post-treatment levels of XPO1 mRNA in patient-derived leukocytes were determined by reverse transcriptase quantitative polymerase chain reaction, and tumor biopsies were examined by immunohistochemistry for changes in markers consistent with XPO1 inhibition. Antitumor response was assessed according Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. Results The most common treatment-related adverse events included fatigue (70%), nausea (70%), anorexia (66%), and vomiting (49%), which were generally grade 1 or 2. Most commonly reported grade 3 or 4 toxicities were thrombocytopenia (16%), fatigue (15%), and hyponatremia (13%). Clinically significant major organ or cumulative toxicities were rare. The maximum-tolerated dose was defined at 65 mg/m2 using a twice-a-week (days 1 and 3) dosing schedule. The recommended phase II dose of 35 mg/m2 given twice a week was chosen based on better patient tolerability and no demonstrable improvement in radiologic response or disease stabilization compared with higher doses. Pharmacokinetics were dose proportional, with no evidence of drug accumulation. Dose-dependent elevations in XPO1 mRNA in leukocytes were demonstrated up to a dose level of 28 mg/m2 before plateauing, and paired tumor biopsies showed nuclear accumulation of key tumor-suppressor proteins, reduction of cell proliferation, and induction of apoptosis. Among 157 patients evaluable for response, one complete and six partial responses were observed (n = 7, 4%), with 27 patients (17%) achieving stable disease for ≥ 4 months. Conclusion Selinexor is a novel and safe therapeutic with broad antitumor activity. Further interrogation into this class of therapy is warranted.
Selinexor in combination with carboplatin and paclitaxel in patients with advanced solid tumors: Results of a single-center, multi-arm phase Ib study. [2022]Carboplatin and paclitaxel (CT) is one of the standard chemotherapy regimens used in various tumor types. Preclinical models have suggested that selinexor, a first-in-class oral potent selective inhibitor of nuclear export Exportin-1, and CT exerts antitumor activity in multiple malignancies.
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]Selinexor is a first-in-class, oral selective inhibitor of nuclear export (SINE) compound which blocks Exportin-1 (XPO1). Our objective was to determine maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of selinexor and weekly paclitaxel.
SINE (selective inhibitor of nuclear export)--translational science in a new class of anti-cancer agents. [2023]Regulation of protein trafficking between the nucleus and cytoplasm represents a novel control point for antineoplastic intervention. Several proteins involved with cellular growth and survival depend on precise and timely positioning within the cell to fulfill their functions, and the nuclear membrane defines one of the most important compartmental barriers. Chromosome Region Maintenance 1, or exportin-1 (CRM1/XPO1), is involved with the export of more than 200 nuclear proteins, and has intriguingly been shown to have an increased expression in several tumor cell types. Selinexor (KPT-330) is a first-in-class selective inhibitor of nuclear export (SINE) to be developed for clinical use. Preclinical data has demonstrated antineoplastic activity of SINE compounds in many human solid and hematologic malignancies. The clinical development of Selinexor provides an excellent model for translational research.
Multi-Institutional Prospective Study of Reirradiation with Proton Beam Radiotherapy for Locoregionally Recurrent Non-Small Cell Lung Cancer. [2022]The management of recurrent NSCLC in the setting of prior radiation therapy is challenging. Proton radiotherapy (PRT) is ideally suited to minimize toxicity to previously irradiated organs. We report the safety/feasibility of PRT for NSCLC reirradiation in a prospective multi-institutional study.
High-precision image-guided proton irradiation of mouse brain sub-volumes. [2021]Proton radiotherapy offers the potential to reduce normal tissue toxicity. However, clinical safety margins, range uncertainties, and varying relative biological effectiveness (RBE) may result in a critical dose in tumor-surrounding normal tissue. To assess potential adverse effects in preclinical studies, image-guided proton mouse brain irradiation and analysis of DNA damage repair was established.
Long-term toxicity following 3D conformal radiation therapy for prostate cancer from the RTOG 9406 phase I/II dose escalation study. [2022]To update the incidence of late toxicity of RTOG 9406, a three-dimensional conformal radiation therapy (3DCRT) dose escalation trial for prostate cancer.
Spatial correlation of linear energy transfer and relative biological effectiveness with suspected treatment-related toxicities following proton therapy for intracranial tumors. [2020]Label="PURPOSE" NlmCategory="OBJECTIVE">The enhanced relative biological effectiveness (RBE) at the end of the proton range might increase the risk of radiation-induced toxicities. This is of special concern for intracranial treatments where several critical organs at risk (OARs) surround the tumor. In the light of this, a retrospective analysis of dose-averaged linear energy transfer (LETd ) and RBE-weighted dose (DRBE ) distributions was conducted for three clinical cases with suspected treatment-related toxicities following intracranial proton therapy. Alternative treatment strategies aiming to reduce toxicity risks are also presented.
Clinical outcomes of radiotherapy for spinal cord ependymoma with adverse prognostic features: a single-center study. [2019]This study evaluated the outcomes of radiotherapy (RT) for spinal ependymoma with adverse features, such as incomplete resection or disseminated disease.
Motexafin gadolinium: a novel radiosensitizer for brain tumors. [2014]Despite advances in the field of oncology, progress for patients with brain metastases and most primary brain tumors has been slow. New efforts to enhance the therapeutic index of radiation therapy are under way, including the use of radiosensitizers. Motexafin gadolinium (Xcytrin) is one such novel agent with several unique properties that enhance the cytotoxic potential of radiation therapy, as well as several chemotherapeutic agents, and possibly has independent cytotoxicity in certain lymphoid malignancies. Motexafin gadolinium is very well tolerated with tumor specific uptake. The rationale for the use of this drug as well as its current and future role as a radiation enhancer in the management of brain tumors is reviewed.
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]Stereotactic radiotherapy (SRT) is an attractive treatment option for patients with brain metastases (BM), sparing healthy brain tissue and likely controlling local tumors. Most previous studies have focused on radiological response or survival. Our randomized trial (NCT02353000) investigated whether quality of life (QoL) is better preserved using SRT than whole-brain radiotherapy (WBRT) for patients with multiple BM. Recently, we published our trial's primary endpoints. The current report discusses the study's secondary endpoints.
Comparison of MR-guided radiotherapy accumulated doses for central lung tumors with non-adaptive and online adaptive proton therapy. [2023]Stereotactic body radiation therapy (SBRT) of central lung tumors with photon or proton therapy has a risk of increased toxicity. Treatment planning studies comparing accumulated doses for state-of-the-art treatment techniques, such as MR-guided radiotherapy (MRgRT) and intensity modulated proton therapy (IMPT), are currently lacking.
Efficacy of X-ray stereotactic radiotherapy on brain metastases and prognostic analysis. [2019]X-ray stereotactic radiotherapy (SRT) is one of the effective treatments for brain metastases (BM). This study was to evaluate the efficacy of SRT on BM, and investigate prognostic factors.
Motexafin gadolinium injection for the treatment of brain metastases in patients with non-small cell lung cancer. [2019]Despite recent advances in technology, targeting, and chemotherapy, brain metastasis from non-small cell lung cancer (NSCLC) remains a significant problem. The vast majority of patients with this diagnosis undergo whole brain radiation therapy (WBRT). However, outcomes are still quite poor with median survivals measured in only months. In an effort to enhance outcomes from external beam radiation treatments, radiosensitizers have been investigated. Motexafin gadolinium (MGd) (Xcytrin, Sunnyvale, CA, USA) is a novel radiation sensitizer with a unique mechanism of action that may increase the therapeutic index of WBRT for patients with brain metastases, particularly in those with NSCLC histologies. Here we review the rationale for the use of this drug as well as its current and future role as a radiation enhancer in the management of NSCLC brain metastasis.