A Study of Different Dosing Schedules of Selinexor in Sarcoma Patients

NCT04811196 | Completed Phase 1 DMC

• 1 other identifier: METSSAR
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

Selinexor, Sarcoma

Outcome Measures

Primary Outcomes (2)

• Incidence of toxicity and safety of Selinexor given on either a metronomic (Arm A) or split dosing (Arm B) schedule: Adverse Events

  Graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Analyses will be performed using descriptive statistics.

  Up to 14 days after completion of study treatment

• Recommended phase 2 dose of Selinexor given metronomically

  Toxicity will be assessed using the NCI CTCAE, version 5.0. Adverse events will be tabulated and summarized by major organ category, grade, anticipation, and drug attribution.

  Up to 28 days

Secondary Outcomes (7)

• Progression-Free Survival (PFS) of metronomic Selinexor

  From date of first dose of selinexor until the date of first documented progression, assessed up to 12 months.

• Objective Response Rate (ORR) of metronomic Selinexor

  From date of first dose of selinexor until the date of first documented progression, assessed up to 12 months.

• Clinical Benefit Rate (CBR) of metronomic Selinexor

  From date of first dose of selinexor until the date of first documented progression, assessed up to 12 months.

• Peak Plasma Concentration (Cmax) of metronomic Selinexor

  Prior to dose on day 1, and at 1, 2, 4, and 24 hours post dose of Cycle 1, and prior to dose on Day 1 of Cycle 2 (each cycle is 28 days).

• Area under the plasma concentration versus time curve (AUC) of metronomic Selinexor

  Prior to dose on day 1, and at 1, 2, 4, and 24 hours post dose of Cycle 1, and prior to dose on Day 1 of Cycle 2 (each cycle is 28 days).

Study Arms (2)

Metronomic dosing

EXPERIMENTAL

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.

Drug: Selinexor

Split dosing

EXPERIMENTAL

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.

Drug: Selinexor

Interventions

Selinexor DRUG

Selinexor

Also known as: KPT-330, XPOVIO

Metronomic dosing; Split dosing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent in accordance with federal, local, and institutional guidelines
• Age \> 18 years.
• Patients must have histologically confirmed locally advanced/unresectable or metastatic STS
• For Arm A the acceptable histologies are MPNST, ESS and LMS
• For Arm B arm all STS histologies are eligible
• Patients must fall into one of the three following categories:
• Show evidence of progressive disease on study entry; or
• Be treatment naïve, but have progressed since diagnosis; or
• Newly diagnosed patients with de novo metastatic measurable disease.
• Patient must have measureable disease as defined by RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Adequate hematopoietic function within 7 days prior to C1D1:
• absolute neutrophil count (ANC) ≥1.0x109/L
• hemoglobin ≥ 90 g/L
• platelet count ≥100 x 109/L

You may not qualify if:

• Has received selinexor or another XPO1 inhibitor previously
• Patients who are pregnant or lactating
• Radiation (except planned or on-going palliative radiation outside of the region of measurable disease), chemotherapy, immunotherapy, any other systemic anticancer therapy, or participation in an investigational anti-cancer study ≤3 weeks prior to initiation of therapy. Mitomycin C and radio-immunotherapy within 6 weeks prior to cycle 1 day 1.
• Major surgery within 4 weeks before initiation of therapy
• Active, ongoing or uncontrolled active infection within one week prior to first dose
• Patients with any gastrointestinal dysfunctions that could interfere with the absorption of Selinexor or patients with significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea;
• Inability or unwillingness to take supportive medications such as anti-nausea and anti anorexia agents as recommended by the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Antiemesis and Palliative Care.
• In the opinion of the Investigator, patients who are significantly below their ideal body weight (Body Surface Area ≤ 1.2m2)
• Concurrent therapy with approved or investigational anticancer therapeutic agents
• Any condition that, in the opinion of the Investigator, would interfere with evaluation of the study regimen or interpretation of patient safety or study results

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Sarcoma; Neurofibrosarcoma; Leiomyosarcoma; Sarcoma, Endometrial Stromal

Interventions

selinexor

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Fibrosarcoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Neoplasms, Muscle Tissue; Neoplasms, Complex and Mixed; Endometrial Stromal Tumors; Endometrial Neoplasms; Uterine Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases

Study Officials

• Albiruni Razak, M.D.

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase 1/1b single centre study with two arms. Arm A is a dose escalation study assessing the safety, tolerability and preliminary antitumor activity of low dose metronomic Selinexor in adult patients with locally advanced/unresectable or metastatic MPNST, endometrial stromal cell sarcomas or angiogenic tumors. This is a dose escalation study and will consist of ascending doses of Selinexor administered metronomically as a single agent. Up to 36 patients will be enrolled in Arm A. Arm B of this study will enroll all soft tissue sarcoma histologies to receive flat dosing Selinexor 40mg in the morning, 20mg in the afternoon and 20mg at night orally on days 1, 8, 15, 22 of a 28-day cycle. Twenty patients will be enrolled to this arm. This pattern will continue until disease progression or unacceptable toxicity. Quality of life assessments will occur at pre-dosing, cycle 2 day 1, cycle 6 day 1 and cycle 12 day 1 for those who remain on study.

Study Record Dates

• First Submitted: January 25, 2021
• First Posted: March 23, 2021
• Study Start: March 29, 2021
• Primary Completion: May 15, 2025
• Study Completion: May 15, 2025
• Last Updated: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)