A Study of Different Dosing Schedules of Selinexor in Sarcoma Patients

Sponsor
University Health Network, Toronto
Study ID
NCT04811196
Phase
PHASE1
Status
Completed

Conditions

  • Endometrial Stromal Sarcoma
  • Leiomyosarcoma
  • Malignant Peripheral Nerve Sheath Tumor (MPNST)
  • Soft Tissue Sarcoma

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

Study Details

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.

Key Dates

Start date
Mar 29, 2021
Status verified
May 2025
Primary completion
May 15, 2025
Completion
May 15, 2025

Study Design

Enrollment
56 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Metronomic dosing
    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.
  • Experimental: Split dosing
    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.

Primary Outcome Measure

Incidence of toxicity and safety of Selinexor given on either a metronomic (Arm A) or split dosing (Arm B) schedule: Adverse Events [ Time Frame: Up to 14 days after completion of study treatment ]

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