56 Participants Needed

Selinexor for Sarcoma

AR
Overseen ByAlbiruni Razak, M.D.
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: University Health Network, Toronto
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 2 JurisdictionsThis treatment is already approved in other countries

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

Dr. Albiruni Razak | Bras DDP

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.
See 14 more

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.
See 7 more

Treatment Details

Interventions

  • Selinexor
Trial OverviewThe 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
2Treatment groups
Experimental Treatment
Group I: Split dosingExperimental Treatment1 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 dosingExperimental Treatment1 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

Find a Clinic Near You

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials
1,555
Recruited
526,000+