Selinexor for Sarcoma

Overseen By Albiruni Razak, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University Health Network, Toronto

Must not be taking: XPO1 inhibitors

Disqualifiers: Pregnancy, Active infection, Gastrointestinal dysfunctions, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 to 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called selinexor to determine its effectiveness in treating soft tissue sarcomas, which are cancers forming in the tissues surrounding bones and organs. The trial aims to assess whether lower doses of selinexor can reduce side effects while maintaining effectiveness. Participants are divided into two groups: one group takes selinexor a few days a week to evaluate its safety for specific sarcoma types, while the other group takes it once a week for any sarcoma type. Individuals with advanced or spreading soft tissue sarcoma that cannot be treated with standard therapies might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot be on other anticancer therapies while participating in the study.

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

Research has shown that selinexor has been studied in 3,111 cancer patients, including 142 with sarcoma. Previous patients demonstrated that selinexor can be effective for various types of cancer. However, like many cancer treatments, it may have side effects.

In studies, selinexor was generally well-tolerated, but some side effects were reported. These can include fatigue, nausea, and low blood cell counts, which are common with many cancer treatments. The FDA has already approved selinexor for treating other cancers, such as multiple myeloma and diffuse large B-cell lymphoma, suggesting it is somewhat safe for humans.

The current trial tests lower doses and different dosing schedules to reduce these side effects. The researchers aim to make the treatment safer and more comfortable for patients. Prospective participants should discuss any concerns and questions with the study team or their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Selinexor is unique because it targets nuclear export, a process that cancer cells often exploit to grow and survive. Unlike traditional chemotherapy or radiation treatments for sarcomas, selinexor works by trapping tumor-suppressing proteins inside the nucleus, forcing cancer cells to self-destruct. Researchers are particularly excited about its potential because it offers a novel mechanism of action compared to the standard options. This could mean a new pathway to treat sarcomas, especially for patients with advanced or resistant forms of the disease.

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

Research has shown that selinexor may help treat various types of cancer, including sarcoma. Studies have found that selinexor can slow tumor growth by trapping proteins that typically aid cancer cell survival. In lab tests, selinexor caused tumor cells to shrink, suggesting its potential usefulness in real-world treatments. One study found that selinexor improved patient outcomes by reducing pain and delaying disease progression. This trial will explore two different dosing strategies for selinexor in patients with sarcoma: metronomic dosing and split dosing. This suggests selinexor might benefit patients with soft tissue sarcomas that do not respond to standard treatments. ^{6 7 8 9 10}

Who Is on the Research Team?

Albiruni Razak, MD

Principal Investigator

Princess Margaret Cancer Centre

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced soft tissue sarcomas that can't be treated with standard therapies. Participants must have certain blood counts, organ functions within specific ranges, and not be pregnant or breastfeeding. They should also agree to use contraception and not have had recent cancer treatments or major surgeries.

Inclusion Criteria

You must have a measurable disease according to the RECIST 1.1 guidelines.

My soft tissue sarcoma type qualifies for Arm B of the study.

I can swallow pills.

Exclusion Criteria

I have not had major surgery in the last 4 weeks.

The doctor thinks you are very underweight for your height.

I have previously been treated with selinexor or a similar drug.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

Treatment

Participants receive Selinexor orally in two different dosing schedules: Arm A with metronomic dosing and Arm B with split dosing, until disease progression or unacceptable side effects.

2 to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3 months.

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Selinexor

Trial Overview The study tests different low doses and schedules of Selinexor taken orally to see if they're effective but cause fewer side effects in sarcoma patients. Arm A will test the drug four days a week on specific sarcoma types, while Arm B involves any soft tissue sarcoma subtype taking it once weekly.

How Is the Trial Designed?

Group I: Split dosing Experimental Treatment 1 Intervention

The second arm of the study is an open-label, non randomized, phase 1b study of selinexor in patients with any histological subtype of STS administered orally one day per week, 40mg in the morning, 20mg in the afternoon and 20mg at night as part of a 28 day cycle. Twenty patients will be accrued to this arm.

Group II: Metronomic dosing Experimental Treatment 1 Intervention

This Arm is an open-label, non-randomized, phase 1 study of metronomic dosing of selinexor in patients with locally advanced or metastatic MPNST, ESS, LMS. Up to seven dose levels of Selinexor will be investigated. Patients will undergo 3+3 based dose escalation to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of Selinexor. Escalating doses of selinexor will be given starting with 2.5 mg (taken orally 4 days in a row followed by 3 days break from treatment, repeating this weekly as part of a 28-day cycle). The first dose for the first 2 patients at each dose level will be staggered by 7 days. Minimum number of patients treated in this trial arm is 18 patients, and maximum 36 patients. Schedule: Selinexor flat dosing with dose levels (DLs) of 2.5mg (DL1), 5mg (DL2), 7.5mg (DL3), 10mg (DL4), 12.5mg (DL5), 15mg (DL6), 17.5mg (DL7). A DL-1 (1.25 mg) is also incorporated.

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?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27458288/

Phase IB Study of Selinexor, a First-in-Class ... - PubMed Selinexor was well tolerated at a 60-mg flat dose on a 3-weeks-on, 1-week-off schedule. There was no clinically meaningful impact of food on ...

2. investors.karyopharm.com investors.karyopharm.com/2021-04-19-Karyopharm-Announces-Publication-of-Health-Related-Quality-of-Life-Outcomes-from-Phase-3-SEAL-Study-of-Selinexor-in-Advanced-Unresectable-Dedifferentiated-Liposarcoma-in-Future-Oncology

The Phase 3 SEAL study suggests that selinexor has ... Treatment with Selinexor Demonstrated Several Potential Clinical Advantages Compared to Placebo, Including Reduction in Pain, Longer Time to ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04811196

A Study of Different Dosing Schedules of Selinexor in ... Preclinical data of Selinexor has shown promising in-vitro tumor regression in sarcoma. In two phase I studies, single agent clinical activity in the form ...

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

Selinexor (KPT-330) Induces Tumor Suppression through ... We show that selinexor treatment results in increased nuclear localization of IκB in sarcoma cell lines. Selinexor then sequesters IκB in the nucleus, where it ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT223187

Phase 1b study of selinexor, a first in class selective ... We undertook this study to determine the safety, tolerability and efficacy of selinexor when combined with doxorubicin in pts with locally advanced or ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2019/212306s000lbl.pdf

Xpovio - accessdata.fda.gov Based on data from animal studies and its mechanism of action, XPOVIO can cause fetal harm when administered to a pregnant woman. Selinexor administration to ...

7. data.niaid.nih.gov data.niaid.nih.gov/resources?id=2126069

Safety Study of KPT-330 (Selinexor) in Patients With ... Phase 1 study to evaluate the safety and tolerability of selinexor and determine the Recommended Phase 2 Dose (RP2D) of selinexor for advanced or metastatic ...

8. xpovio.com xpovio.com/

XPOVIO® (selinexor) | For Adults with MM and DLBCL XPOVIO® is an oral medicine used to treat adults with multiple myeloma or relapsed/refractory diffuse large B-cell lymphoma. See full safety information.

9. oncologynewscentral.com oncologynewscentral.com/drugs/monograph/177518-319029/selinexor-oral

Selinexor: uses, dosing, warnings, adverse events, ... The current indication for selinexor is based principally on efficacy and safety data from a prespecified subgroup analysis of 83 patients who were enrolled ...

10. drugs.com drugs.com/selinexor.html

Selinexor: Uses, Dosage, Side Effects, Warnings Selinexor (Xpovio) is a once or twice-weekly tablet for adults with multiple myeloma or resistant diffuse large B-cell lymphoma.