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

56 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase 1, open-label, single centre study of investigational drug selinexor in participants with soft tissue sarcomas that cannot be treated with standard therapies. Selinexor has been given to 3111 participants with cancer to date including 142 sarcoma patients. Early findings have shown that selinexor is effective in multiple cancer types. The current study is being done to test low doses and different dosing schedules of selinexor to find out if it reduces the side effects without compromising the benefits. This study has 2 groups or Arms: Arm A and Arm B. Arm A (Dose escalation Arm): Participants will receive selinexor by mouth 4 days a week to find out the safety, tolerability and anti-tumor effect of low doses of Selinexor in participants with advanced or metastatic malignant peripheral nerve sheath tumors (MPNST), endometrial stromal sarcomas (ESS) and leiomyosarcoma (LMS). Participants will continue on study until disease progression or unacceptable side effects. Up to 36 participants will be enrolled in this Arm. Arm B: Participants with any soft tissue sarcoma subtypes will be enrolled in this Arm. They will receive flat doses of Selinexor by mouth once weekly, 3 times a day. Safety and tolerability will be assessed in this Arm. Up to 20 participants will be enrolled and they will continue to receive selinexor until disease progression or unacceptable side effects. Cancer is the uncontrolled growth of human cells. One of the ways cancers cells continue to grow is by getting rid of proteins called "tumor suppressor proteins" that would normally cause cancer cells to die. The study drug works by trapping "tumor suppressor proteins" within the cell, causing the cancer cells to die or stop growing. The study comprises 3 periods: Screening (up to 28 days), Study Drug (until disease progression), and Survival Follow-Up (once every 3 months). Procedures for research purposes only will include blood collection and study questionnaire.

Research Team

Albiruni Razak, MD

Principal Investigator

Princess Margaret Cancer Centre

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+