A Phase 1 interventional study of Selinexor in Soft Tissue Sarcoma, Malignant Peripheral Nerve Sheath Tumor (MPNST) and Leiomyosarcoma, sponsored by University Health Network, Toronto. Completed at 1 site in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-05-29.
Sponsored by University Health Network, Toronto · Phase 1, Interventional, and Treatment
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.
Background:
Soft tissue sarcomas (STS):
STS are a group of heterogeneous mesenchymal derived tumors with many histological types that account for approximately 1% of adult tumors and 15% of pediatric tumors. STS can be divided into those with simple genetic alterations (e.g. translocations or activating mutations) or karyotypic complex lesions. However, most subclasses are treated in the same manner. Surgery is the primary treatment for localized STS, with or without radiation therapy (RT), but approximately 10% of patients will present with metastatic disease.
For patients who present with metastatic disease, or those with locally advanced/unresectable or have failed primary therapy, cytotoxic chemotherapy is usually the treatment of choice which may provide meaningful palliation or prolong survival. Traditionally, doxorubicin containing regimens, in combination with ifosfamide or as a single agent are standard first line therapies. Combination based doxorubicin containing regimens have shown higher response rates and progression free survival at the expense of more toxicity when compared to doxorubicin alone. However, no combination regimen has been associated with increased overall survival compared to doxorubicin alone.
In the metastatic setting, STS carry a poor prognosis related to a lack of chemo-sensitivity and a lack of systemic therapeutic options. Exportin 1 (XPO1 or chromosome region maintenance 1 [CRM1]) is the sole nuclear exporter of some tumor suppressor proteins (TSP). XPO1 is over-expressed 2-4 fold in a variety of solid and hematological tumors with higher levels correlating with poorer outcomes.
Selinexor:
Selinexor is a novel, oral, small-molecule XPO1 inhibitor which forces reactivation of TSPs and thus leads to apoptosis of tumor cells. 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 of prolonged stable disease was seen in STS. Twice weekly dosing aided tolerability with a MTD declared at 65mg/m2 for solid tumors and 60mg flat dosing was the RP2D based on better tolerability given problems related to gastrointestinal toxicity however these doses were still difficult for patients to take due to the toxicity profile. A Phase 1b study has been performed combining Selinexor once weekly oral dosing with doxorubicin given at the standard 3 weekly dose in advanced soft tissue sarcoma.
Previous studies have provided a signal of increased likelihood of benefit to particular subtypes including metastatic malignant peripheral nerve sheath tumors (MPNST) and endometrial stromal sarcomas (ESS). In the early phase studies, objective responses or prolonged stable disease were demonstrated (n=3 for both MPNST and ESS). In this study, the investigator also plans to include leiomyosarcoma (LMS) - such strategy will allow not only seamless recruitment, but also generate treatment efficacy data for other rare types of sarcomas.
Additionally, preclinical data has shown efficacy in using metronomic dosing of Selinexor. The investigator hypothesizes that low dose Selinexor will improve tolerability of the drug without impacting the clinical benefit that has been seen in other studies for patients with particular histological subtypes of STS.
Rationale:
Biological Rationale:
More than 2500 patients with advanced cancers have received Selinexor orally in Phase 1 and Phase 2-3 studies as of 31 May 2019. Based on the preclinical and clinical findings to date, Selinexor dosing is limited to ≤70 mg/m2 (≤120 mg) maximum dose in adults. The plan going forward is that Selinexor will be administered primarily as fixed milligram doses, as analyses of Phase 1 pharmacokinetic (PK) data indicated that exposure is not strongly correlated with Body Surface Area (BSA).
An interim analysis of preliminary results was performed to determine the RP2D for future studies. The results of this analysis suggest that, overall, Selinexor doses > 65 mg do not appear to provide additional efficacy responses beyond those seen with the 60 mg dose (described herein as 45-65 mg dose level, median 60 mg) with the exception of activity in refractory multiple myeloma (MM), where the RP2D is Selinexor 80 mg in combination with 20mg dexamethasone. Importantly, response results with Selinexor 45-65 mg twice weekly were comparable for both hematologic malignancies (excluding MM) and solid tumors.
The currently available selinexor formulation (20 mg tablet) and dosage is quite toxic particularly in terms of gastrointestinal disturbance, particularly nausea and vomiting. As a result of these difficulties it might be beneficial to investigate alternate formulations of selinexor or a different dosing schedule of the currently available selinexor formulation. A PK study in male Beagle dogs has been completed by Karyopharm investigating a new extended release (ER) formulation of Selinexor 20 mg tablets showing favorable results.
Dose Schedule Rationale:
In the present study, Selinexor will be given using two different schedules according to Schema for Arm A (metronomic) and Schema for Arm B (split dosing).
In Arm A Selinexor will be administered at a fixed oral dose as per dose level (starting at 2.5mg PO 4 days on, 3 days off repeated weekly) of each 4-week (28-day) cycle a total of 16 doses per cycle. The maximum dose for Selinexor in this study will be 17.5mg PO flat dosing 4 days on, 3 days off, weekly. This arm of the study will be aimed at identifying the RP2D and toxicity profile of this new selinexor dosing schedule.
In Arm B patients will be treated with Selinexor 40mg in the morning, 20mg in the afternoon and 20mg at night on days 1, 8, 15 and 22 of a 28-day cycle. The hope is that this alternate dosing schedule will improve the tolerability of this formulation of selinexor without impacting its clinical benefit.
Intervention and mode of delivery:
In Arm A patients will receive Selinexor orally as described above. The initial 3 patients will be enrolled to the first Selinexor dose level of 2.5mg (DL1). Three patients will be assessed per cohort for at least 1 cycle and dose escalation or de-escalation rules will follow 3+3 dosing. The first dose of study treatment for the first two patients will be staggered by 7 days. Intra-patient dose escalation is not permitted at any time during the treatment plan.
In Arm B also patients will receive selinexor orally as described above.
Duration of Intervention and Evaluation:
Treatment in both arms with Selinexor will be repeated on a 28-day cycle until radiographic or symptomatic progression on imaging or the development of unacceptable toxicity. Patients will be restaged every 2 cycles until unacceptable toxicity or disease progression. Subsequent follow-up for disease progression will continue by telephone or review of patient medical records for up to 2 years after the completion of trial treatment.
Number of Patients:
A total of up to 36 patients will be accrued in Arm A. Up to 20 patients will be enrolled in Arm B with an anticipated accrual period of 12 to 18 months.
Definition of dose limiting toxicity (DLT):
DLT is defined as any of the following occurring in the first 28 days of each dose level that is considered at least possibly related to drug administration:
≥ 4 missed doses (out of 16) due to a toxicity that is at least possibly study drug related.
Discontinuation of a patient due a toxicity that is at least possibly study drug related before completing cycle 1
Non-Hematologic:
Grade ≥ 3 nausea/vomiting, dehydration or diarrhea while taking optimal supportive medications Grade 3 fatigue lasting for ≥ 7 days while taking optimal supportive care and with correction of dehydration, anorexia, anemia, endocrine, or electrolyte abnormalities.
Grade 3 AST or ALT elevation lasting longer than 7 days OR Grade 3 AST or ALT elevation in the setting of bilirubin elevation > 2x ULN (> 2X baseline for patients with Gilbert's syndrome) OR any grade 4 AST or ALT elevation.
Any other clinically significant Grade ≥ 3 non-hematological toxicity except alopecia or electrolyte abnormalities correctable with supportive therapy Any cardiac disorder ≥ CTCAE Grade 3
Hematologic:
Grade 4 neutropenia [absolute neutrophil count (ANC) \< 0.5x109/L] on Cycle 2 Day 1 that does not resolve to G1 within 7 days Grade 4 neutropenia [absolute neutrophil count (ANC) \< 0.5x109/L] within the first 28 days lasting ≥ 7 days Grade 3 Febrile neutropenia Grade ≥ 3 thrombocytopenia associated with clinically significant bleeding Grade 4 thrombocytopenia within the first 28 days (platelets \< 25x109/L) lasting > 7days
Other:
Any hematologic or non-hematologic toxicity that results in the inability to administer day 1 of the next planned cycle within 14 days of the planned end of the previous cycle.
Treatment related death During the dose escalation portion of the study, patients who missed >1 dose of Selinexor during Cycle 1 for reasons unrelated to study drug are not evaluable for DLT and will be replaced.
Treatment Discontinuation Criteria:
Disease progression Noncompliance with protocol Need for treatment with medications not allowed by the study protocol Consent withdrawal Intercurrent illness Incidence or severity of AEs Investigator discretion
Duration:
The treatment period for an individual patient is expected to be approximately between 2 and 12 months, however there is no maximum treatment duration.
Study procedures:
For Arm A the starting dose of Selinexor will be 2.5mg given 4 days on 3 days off on a weekly basis as part of a 28-day cycle. For Arm B patients will receive oral Selinexor 40 mg in the morning, 20 mg in the afternoon, 20 mg in the evening. Patients will be assessed for response after ever 2 cycles. Treatment will be given until disease progression or unacceptable toxicity.
Safety data:
Overall safety profile as per NCI CTCAE version 5.
Concomitant Medications:
Patients will receive best supportive care, including anti-emetics, appetite stimulants and growth factors, blood product transfusions, antimicrobials and (as appropriate) granulocyte colony-stimulating factors (G-CSF) for neutropenia and/or neutropenic infection, erythropoietin for anemia, and/or platelet-stimulating factors for thrombocytopenia. Patients will not be dosed with G-CSF in the first cycle for primary prophylaxis of febrile neutropenia.
If clinically indicated and as required by protocol, patients may receive red blood cell or platelet transfusions, acetaminophen, serotonin (5-HT3) receptor subtype antagonists (e.g., ondansetron) megestrol acetate, and olanzapine in addition to ondansetron. Patients intolerant to 5-HT3 antagonists may receive D2-antagonists instead. Additional anti-nausea and anti-anorexia agents may be given as needed. Patients may continue to receive baseline medication(s), and may receive concomitant medications that are medically necessary as standard care to treat co-morbid diseases, AEs, and intercurrent illnesses.
Concurrent therapy with any other approved or investigative anticancer therapy is not allowed.
Pharmacokinetic and Pharmacodynamic assessments:
PK will be determined at various times following administration of Selinexor in Arm A.
Pharmacokinetics:
In the metronomic arm for the first 3 patients in each dose level, blood samples just before Selinexor administration (C1D1), and at 1hr, 2hr, 4hr, 24hr and a trough level pre C2 will be collected.
Response:
Objective disease response assessment will be made according to standard, international RECIST 1.1 criteria for solid tumors.
Safety Variables and Analysis:
The safety and tolerability of Selinexor will be evaluated by means of drug related DLT, AE reports, physical examinations, and clinically significant laboratory safety evaluations. NCI CTCAE version 5.0 will be used for grading of AEs.
Investigators will provide their assessment of causality as: unrelated, possibly related, or probably or definitely related for all AEs.
1,607 studies on the registry are indexed under Sarcoma; 366 are open to participants now.
This study's enrollment of 56 is above the median of 40 across 1,255 interventional studies indexed under Sarcoma.
Browse Sarcoma studies →University Health Network, Toronto is the lead sponsor of 1,438 studies on the registry; 297 are open to participants now.
Of its 17 completed or terminated interventional studies of FDA-regulated products, 3 (18%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients must have confirmed locally advanced/unresectable or STS
Patients must fall into one of the three following categories:
Adequate hematopoietic function within 7 days prior to C1D1:
i. At least a 2-week interval from the last red blood cell (RBC) transfusion prior to the Screening hemoglobin assessment, and
ii. At least a 1-week interval from the last platelet transfusion prior to the Screening platelet assessment.
iii. However, patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study.
Adequate hepatic function within 28 days prior to C1D1:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
Selinexor
Also known as: KPT-330, XPOVIO
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.
Time frame: 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.
Time frame: Up to 28 days
Progression-Free Survival (PFS) of metronomic Selinexor
The Kaplan-Meier product limit method will be used to estimate PFS of the median PFS and PFS rates at clinically relevant time point will be provided with the 95% CI.
Time frame: 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
Defined as the proportion of patients who achieved a complete response (disappearance of all target tumors) or a partial response (PR) (≥30% decrease in the sum of longest diameters of target tumors) based on RECIST Version 1.1. The ORR, along with exact two-sided 95% confidence intervals based on binomial distribution will be reported.
Time frame: 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
Defined as the proportion of patients who achieved a complete response (disappearance of all target tumors) or a partial response (≥30% decrease in the sum of the longest diameters of target tumors) or stable disease (Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD) for greater than 16 weeks based on RECIST Version 1.1. The CBR, along with exact two-sided 95% confidence intervals based on binomial distribution will be reported.
Time frame: 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
Descriptive statistics will be used to summarize Selinexor concentration at each sampling time point and Cmax. Only the first 3 patients per dose level will be included for Cmax analysis.
Time frame: 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
Descriptive statistics will be used to summarize AUC of Selinexor. Only the first 3 patients per dose level will be included for AUC analysis.
Time frame: 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).
Characterization of the toxicity of metronomic Selinexor
Analyses will be performed for all patients having received at least one dose of study drug. The study will use the NCI CTCAE v5.0. Serious adverse events, AEs, AEs leading to withdrawal/dose interruptions/dose modification will be summarized using descriptive statistics.
Time frame: Up to 14 days after completion of study treatment
Quality of life assessment using Quality of Life Questionnaire
To better define the toxicity of Selinexor, patient reported outcomes using 'European Organization for Research and Treatment of Cancer' (EORTC) 'Quality of Life Questionnaire' (QLQ-C30) will be investigated. The score ranges from 1 to 4, with 1 being the worst outcome and 4 being the best. Mean score of individual item numbers of interest will be analyzed with descriptive and mixed effect model methods.
Time frame: Screening and then pre-dose Cycles 1, 6, and 12 (each cycle is 28 days).
Plan to share: No
No publications or documents are linked to this record.
Ran from Mar 2021 to primary completion in May 2025, 49 months.
Of 89 non-industry phase 1 interventional studies under Sarcoma, half reached primary completion within 62 months of starting (the median), counting those still running; a quarter within 34 and three quarters within 77. This study's 49 months is below that.
Counting every sponsor, half of 161 studies reached it within 56 months; a quarter within 35 and three quarters within 72.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in May 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Selinexor
University Health Network, Toronto →