Selinexor for Solid Tumors

Recruiting at 14 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

36 Participants Needed

Trial Summary

What is the purpose of this trial?

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, MPNST, or another solid tumor that makes a higher than normal amount of XPO1 or has genetic changes that increase the activity of XP01.

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.

What data supports the effectiveness of the drug Selinexor for treating solid tumors?

Research shows that Selinexor, an oral drug that blocks a protein called Exportin 1, has shown antitumor activity in various cancers, including solid tumors. In studies, some patients with advanced solid tumors experienced tumor shrinkage or disease stabilization when treated with Selinexor. ^{1 2 3 4 5}

What makes the drug Selinexor unique for treating solid tumors?

Selinexor is unique because it is a first-in-class, oral drug that works by blocking Exportin-1 (XPO1), a protein that helps cancer cells grow by exporting tumor-suppressor proteins out of the cell nucleus. This mechanism is different from many other cancer treatments, which often target the cancer cells directly rather than their export pathways. ^{1 2 3 4 5}

Research Team

Michael Ortiz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. 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]

2. United States 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. [2023]

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

Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies. [2023]

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

Selinexor: First Global Approval. [2023]