Selinexor for Solid Tumors

Recruiting at 18 trial locations

Overseen By Julia Glade Bender, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: XPO1 inhibitors

Disqualifiers: Uncontrolled infection, Solid organ transplant, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if selinexor, a potential new drug, can effectively treat certain solid tumors, such as Wilms tumor, rhabdoid tumor, and MPNST, particularly when these tumors resist other treatments. Researchers are testing selinexor for its ability to target tumors that overproduce a protein called XPO1 or have changes that increase XPO1's activity. Suitable participants have tumors that have recurred or do not respond to treatment and have specific types of Wilms, rhabdoid, or MPNST tumors. Participants should have tried at least one cancer treatment before joining this trial. As a Phase 2 trial, this research focuses on measuring selinexor's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, there are specific 'washout' periods (time without taking certain medications) for prior anti-cancer therapies, ranging from 7 to 84 days, depending on the type of treatment.

Is there any evidence suggesting that selinexor is likely to be safe for humans?

Research has shown that selinexor yields promising results in treating solid tumors. In earlier studies, selinexor was tested on various types of solid tumors and helped delay cancer progression. This indicates its potential effectiveness.

Regarding safety, selinexor is generally well-tolerated. In a study involving children with recurring or hard-to-treat solid tumors, selinexor proved effective when taken orally and could reach the brain, which is crucial for treating certain tumors. While some side effects like tiredness and nausea occurred, they were mostly mild to moderate.

Selinexor is still under study for use in various tumors, including Wilms tumor and other solid tumors. Researchers continue to gather data to confirm its safety and effectiveness. Clinical trial participants are closely monitored to manage any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for solid tumors?

Unlike the standard treatments for solid tumors, which often include surgery, chemotherapy, or radiation, Selinexor offers a unique approach by targeting the nuclear export of tumor suppressor proteins. This means it works at the cellular level to prevent cancer cells from growing and dividing. Researchers are excited because Selinexor has shown potential in overcoming resistance to conventional therapies, offering hope for patients who have not responded to existing treatments.

What evidence suggests that selinexor might be an effective treatment for solid tumors?

Research suggests that selinexor may effectively treat various solid tumors. In this trial, participants will be divided into cohorts based on their specific tumor type. For those with Wilms tumors, studies have shown that selinexor can significantly extend the time patients live without disease progression. In the rhabdoid tumor cohort, early tests indicate that selinexor can greatly slow tumor growth. For participants with MPNST, studies found that selinexor controlled the disease in 84% of patients. Selinexor works by blocking a protein called XPO1, which can stop tumor cells from growing and may help kill them. Overall, selinexor shows promise in treating these challenging cancers. ^{5 6 7 8 9}

Who Is on the Research Team?

Michael Ortiz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for people under 51 with certain relapsed/refractory solid tumors, including Wilms tumor and rhabdoid tumor. Participants must be over 6 months old, have recovered from previous cancer treatments, and meet specific health criteria related to organ function. Pregnant or breastfeeding women can't join, nor can those who've had prior treatment with XPO1 inhibitors.

Inclusion Criteria

I am mostly able to care for myself and carry on normal activities.

My liver functions are within the required range.

My kidney function is good, with a GFR of 50 or higher.

Exclusion Criteria

Pregnant or breast-feeding women will not be entered on this study because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal.

Patients who as a result of serious medical, psychiatric, and/or social situation(s), in the opinion of the investigator, may not be able to comply with supportive care, safety monitoring, or any other key requirements of the study protocols are not eligible.

I do not have an uncontrolled infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive selinexor for the treatment of relapsed/refractory Wilms tumor and other solid tumors

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Selinexor

Trial Overview

The study tests Selinexor's effectiveness on patients with solid tumors that produce excess XPO1 or have genetic changes increasing XPO1 activity. It includes different age groups (cohorts) to assess the drug's pharmacokinetics (how it moves through the body) before moving onto phase II where its efficacy is measured.

How Is the Trial Designed?

Group I: Cohort D.1 Other Solid Tumor Experimental Treatment 1 Intervention

Participants must not qualify for Cohorts A, B, or C but have a solid tumor (no hematologic malignancies including lymphoma) for which there is specific evidence that this particular patient's tumor may benefit from selinexor.

Group II: Cohort C.1 MPNST Experimental Treatment 1 Intervention

Participants will have progressive, relapsed, unresectable or metastatic MPNST

Group III: Cohort B.1 Rhabdoid Tumor Experimental Treatment 1 Intervention

Participants will have any Rhabdoid tumor

Group IV: Cohort A.1 Wilms Tumor Experimental Treatment 1 Intervention

Participants will have any type of Wilms tumor or nephroblastoma

Selinexor is already approved in United States, Canada for the following indications:

Approved in United States as Xpovio for:

• Multiple myeloma
• Diffuse large B-cell lymphoma

Approved in Canada as Xpovio for:

• Multiple myeloma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

In a phase 2 trial involving 114 patients with heavily pretreated recurrent gynecological cancers, selinexor showed a disease control rate of 30%, indicating its potential effectiveness as a treatment option for ovarian and endometrial cancers.

Common side effects included thrombocytopenia and fatigue, but these were manageable and reversible, with lower-grade adverse events observed in patients receiving a once-weekly dosing schedule compared to twice-weekly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies. Vergote, IB., Lund, B., Peen, U., 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 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 (XPOVIO™) is a novel oral medication that inhibits Exportin-1 (XPO1) and has been approved for treating relapsed or refractory multiple myeloma (RRMM) in adults, marking a significant advancement in cancer therapy.

The drug is currently being tested for effectiveness in various other types of blood and solid tumors, indicating its potential as a versatile treatment option in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor: First Global Approval. Syed, YY.[2023]

Selinexor, an inhibitor of the exportin 1 (XPO1) receptor, showed significant cytotoxic activity against various solid tumors and acute lymphoblastic leukemia (ALL) xenografts in a study involving in vitro and in vivo testing, with 76% of solid tumor models and 63% of ALL models showing improved event-free survival.

The treatment resulted in objective responses in 4 out of 38 solid tumor xenografts and 25% of ALL xenografts, indicating its potential effectiveness, particularly in tumors with specific genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamic and genomic markers associated with response to the XPO1/CRM1 inhibitor selinexor (KPT-330): A report from the pediatric preclinical testing program. Attiyeh, EF., Maris, JM., Lock, R., et al.[2023]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8018316/

Selinexor, a First in Class, Nuclear Export Inhibitor for the ...

In this article, we report nine cases of MPNST treated with selinexor, an orally bioavailable, selective inhibitor of nuclear export, accompanied by tumor ...

2.

theoncologist.onlinelibrary.wiley.com

theoncologist.onlinelibrary.wiley.com/doi/pdf/10.1002/onco.13692

Selinexor, a first in class, nuclear export inhibitor for the ...

Onco- logic outcomes of sporadic, neurofibromatosis- associated, and radiation-induced malignant peripheral nerve sheath tumors. Ann Surg Oncol. 2013;20:66–72.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04811196

A Study of Different Dosing Schedules of Selinexor in ...

Previous studies have provided a signal of increased likelihood of benefit to particular subtypes including metastatic malignant peripheral nerve sheath tumors ...

4.

aacrjournals.org

aacrjournals.org/clincancerres/article/23/15/4301/257874/Selinexor-KPT-330-Induces-Tumor-Suppression

Selinexor (KPT-330) Induces Tumor Suppression through ...

Abstract. Purpose: Selinexor, a small molecule that inhibits nuclear export protein XPO1, has demonstrated efficacy in solid tumors and hematologic.

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S0959804920313228

A phase 1b trial of selinexor, a first-in-class selective ...

Among the 24 evaluable patients for disease response, 5 (21%) had a partial response and 15 (63%) had SD as best response with a disease control rate of 84% ( ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05985161

NCT05985161 | A Study of Selinexor in People With Wilms ...

The purpose of this study is to find out whether selinexor is an effective treatment for people who have a relapsed/refractory Wilms tumor, rhabdoid tumor, ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05985161?cond=Neurofibrosarcoma%20OR%20%22neurosarcoma%22%20OR%20%22%20neurosarcoma%20%5Bobs%5D%22&aggFilters=status:not%20rec&viewType=Table&rank=8

A Study of Selinexor in People With Wilms Tumors and ...

The purpose of this study is to find out whether selinexor is an effective treatment for people who have a relapsed/refractory Wilms tumor, rhabdoid tumor, ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4722540/

a report from the Pediatric Preclinical Testing Program - PMC

Selinexor induced significant differences in event-free survival (EFS) distribution in 29 of 38 (76%) of the evaluable solid tumor xenografts and in 5 of 8 (63 ...

9.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12045713/

Phase 1 trial of selinexor in pediatric recurrent/refractory solid ...

Selinexor is orally bioavailable, CNS penetrant, and has shown preclinical efficacy in multiple pediatric cancer models, including HGG, as well as other CNS and ...