This is a randomized, multicenter, double-blind, placebo-controlled, Phase 2-3 study of patients diagnosed with advanced unresectable dedifferentiated liposarcoma. Approximately 342 total patients will be randomized to study treatment (selinexor or placebo).
In the Phase 2 portion of the study, 57 patients were randomized to selinexor (60 mg) or placebo at a 1:1 allocation ratio. In the Phase 3 portion of the study, approximately 285 patients will be randomized to selinexor (60 mg) or placebo with a 2:1 allocation ratio. Patients who progress during the blinded portion of the study will be unblinded and if receiving: * placebo, may cross over to open-label selinexor (60mg twice-weekly) * selinexor, will be withdrawn from further treatment and followed for survival Study treatment will be given twice-weekly on Day 1 and Day 3 during Weeks 1-6 of each six-week (42 day) cycle until disease progression or intolerability. Treatment will continue until one or more of the following occurs: * Disease progression, as defined by RECIST v1.1 Response Criteria * Clinical progression, as determined by the treating physician * Unacceptable adverse events (AEs) or failure to tolerate study treatment * Patient withdrawal * Patient discontinuation due to non-compliance
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
342
Phase 3 Double Blind: Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
PFS was defined as the time from the date of randomization until the first date of Independent Review Committee (IRC)-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20% increase in the sum of the longest diameter (SLD), taking as reference the smallest sum of the longest diameter (SLD) recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From the date of randomization until the first date of disease progression, or death due to any cause whichever occurred first (up to 57 months)
Phase 3 Open Label: Progression-free Survival (PFS) as Per RECIST Version 1.1
PFS was defined as the time from the date of randomization in the Phase 3 open-label period until the first date of IRC-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From the date of randomization in the Phase 3 open label period until the first date of disease progression, or death due to any cause whichever occurred first (up to 57 months)
Phase 2 Double Blind: Progression-free Survival (PFS) as Per RECIST Version 1.1
PFS was defined as the time from date of randomization until the first date of IRC-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 57 months)
Phase 2 Open Label: Progression-free Survival (PFS) as Per RECIST Version 1.1
PFS was defined as the time from date of randomization in the Phase 2 open-label period until the first date of IRC-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
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Cedars-Sinai Medical Center
Los Angeles, California, United States
University of California, Los Angeles
Los Angeles, California, United States
Sarcoma Oncology Center
Santa Monica, California, United States
Stanford University
Stanford, California, United States
University of Colorado-Denver
Denver, Colorado, United States
Yale Cancer Center
New Haven, Connecticut, United States
Mayo Clinic
Jacksonville, Florida, United States
Northwestern Memorial Hospital
Chicago, Illinois, United States
Johns Hopkins
Baltimore, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
...and 61 more locations
Time frame: From date of randomization in the Phase 2 open label period until the first date of PD or death due to any cause, whichever occurred first (up to 57 months)
Phase 3 Double Blind: Overall Survival (OS)
OS was defined as the duration (in months) from the date of randomization to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier.
Time frame: From date of randomization until death due to any cause, whichever occurred first (up to 70 months)
Phase 3 Open Label: Overall Survival (OS)
OS was defined as the duration (in months) from the date of randomization in the Phase 3 open-label period to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier.
Time frame: From date of randomization in phase 3 open label period until death due to any cause, whichever occurred first (up to 70 months)
Phase 2 Double Blind: Overall Survival (OS)
OS was defined as the duration (in months) from the date of randomization to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier.
Time frame: From the date of randomization until death due to any cause, whichever occurred first (up to 70 months)
Phase 2 Open Label: Overall Survival (OS)
OS was defined as the duration (in months) from the date of randomization in the Phase 2 open-label period to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier.
Time frame: From date of randomization in the Phase 2 open-label period until death due to any cause, whichever occurred first (up to 70 months)
Phase 3 Double Blind: Time-to-Progression (TTP) as Per RECIST Version 1.1
TTP was defined as the time from date of randomization until ICR-determined PD per RECIST version 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 70 months)
Phase 3 Open Label: Time-to-Progression (TTP) as Per RECIST Version 1.1
TTP was defined as the time from date of randomization in the Phase 3 open-label period until ICR-determined PD per RECIST version 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From date of randomization in the Phase 3 open label period until the first date of PD or death due to any cause, whichever occurred first (up to 70 months)
Phase 2 Double Blind: Time-to-Progression (TTP) as Per RECIST Version 1.1
TTP was defined as the time from date of randomization until ICR-determined PD as per RECIST version 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 70 months)
Phase 2 Open Label: Time-to-Progression (TTP) as Per RECIST Version 1.1
TTP was defined as the time from date of randomization in the Phase 2 open-label period until ICR-determined PD per RECIST version 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From date of randomization in the Phase 2 open-label period until the first date of PD or death due to any cause, whichever occurred first (up to 70 months)
Phase 3 Double Blind: Overall Response Rate (ORR)
ORR was defined as the percentage of participants who achieved complete response (CR) or partial response (PR), per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From date of randomization until the documentation of CR or PR (up to 70 months)
Phase 3 Open Label: Overall Response Rate (ORR)
ORR was defined as the percentage of participants who achieved CR or PR, per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From date of randomization in the Phase 3 open label period until the documentation of CR or PR (up to 70 months)
Phase 2 Double Blind: Overall Response Rate (ORR)
ORR was defined as the percentage of participants who achieved CR or PR, per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From date of randomization until the documentation of CR or PR (up to 70 months)
Phase 2 Open Label: Overall Response Rate (ORR)
ORR was defined as the percentage of participants who achieved CR or PR, per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From date of randomization in the Phase 2 open-label period until the documentation of CR or PR (up to 70 months)
Phase 3 Double Blind: Duration of Response (DOR)
DOR was defined as the time from first occurrence of CR or PR until the first date of PD per RECIST version 1.1 or death. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From first occurrence of CR or PR until the first date of PD (up to 70 months)
Phase 3 Double Blind: Progression-free Survival (PFS) as Per Investigator Assessment
PFS was defined as the time from date of randomization until the first date of PD, per RECIST version 1.1, or death due to any cause as defined by the Investigator based on clinical and/or radiologic criteria. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From the date of randomization until the first date of disease progression, or death due to any cause whichever occurred first (up to 70 months)
Phase 3 Double Blind: Time to Next Treatment (TTNT)
TTNT was defined as time since randomization until the first new antineoplastic therapy or death due to any cause, whichever occurs first.
Time frame: Time from randomization to the first new antineoplastic therapy or death due to any cause (up to 70 months)
Phase 2 Double Blind: Time to Next Treatment (TTNT)
TTNT was defined as time since randomization until the first new antineoplastic therapy or death due to any cause, whichever occurs first.
Time frame: Time from randomization to the first new antineoplastic therapy or death due to any cause (up to 70 months)
Phase 3 Double Blind: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE was defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both serious and non-serious TEAEs.
Time frame: From start of study drug administration up to 70 months
Phase 3 Open Label: Number of Participants With TEAEs and Serious TEAEs
An adverse event was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both serious and non-serious TEAEs.
Time frame: From start of study drug administration up to 70 months
Phase 2 Double Blind: Number of Participants With TEAEs and Serious TEAEs
An adverse event was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both serious and non-serious TEAEs.
Time frame: From start of study drug administration up to 70 months
Phase 2 Open Label: Number of Participants With TEAEs and Serious TEAEs
An adverse event was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both serious and non-serious TEAEs.
Time frame: From start of study drug administration up to 70 months
Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30)
The QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of patients with cancer. QLQ-C30 contains 30 questions that include five functional scales (physical, role, emotional, social, and cognitive functioning); three symptom scales (fatigue, nausea/vomiting and pain); six single-item symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties); and global health status/quality of life (QoL). Most questions used a 4-point scale (from 1 'Not at all' to 4 'Very much'); 2 questions used a 7-point scale (from 1 'very poor' to 7 'Excellent'). Scores were averaged and transformed to a 0-100 scale. For the functional scales and the global health status/QoL, a higher score represents a better level of functioning (better health status); for the symptom scales/items, a higher score represents a higher level of symptomatology/problems (worse health status).
Time frame: Baseline up to Day 1387
Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30)
The QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of patients with cancer. QLQ-C30 contains 30 questions that include five functional scales (physical, role, emotional, social, and cognitive functioning); three symptom scales (fatigue, nausea/vomiting and pain); six single-item symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties); and global health status/quality of life (QoL). Most questions used a 4-point scale (from 1 'Not at all' to 4 'Very much'); 2 questions used a 7-point scale (from 1 'very poor' to 7 'Excellent'). Scores were averaged and transformed to a 0-100 scale. For the functional scales and the global health status/QoL, a higher score represents a better level of functioning (better health status); for the symptom scales/items, a higher score represents a higher level of symptomatology/problems (worse health status).
Time frame: Baseline up to Day 379