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Trial record 1 of 2 for:    selinexor liposarcoma
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Selinexor in Advanced Liposarcoma (SEAL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02606461
Recruitment Status : Completed
First Posted : November 17, 2015
Results First Posted : December 7, 2021
Last Update Posted : January 23, 2023
Sponsor:
Information provided by (Responsible Party):
Karyopharm Therapeutics Inc

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Dedifferentiated Liposarcoma Drug: Selinexor Drug: Placebo Phase 2 Phase 3

Detailed Description:

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  • selinexor, will be withdrawn from further treatment and followed for survival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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 342 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2-3, Multicenter, Randomized, Double-blind Study of Selinexor (KPT-330) Versus Placebo in Patients With Advanced Unresectable Dedifferentiated Liposarcoma (DDLS)
Actual Study Start Date : January 4, 2016
Actual Primary Completion Date : October 28, 2020
Actual Study Completion Date : October 26, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Selinexor

Arm Intervention/treatment
Experimental: Phase 2 Double-blinded: Selinexor
Participants received a fixed blinding dose of 60 milligrams (mg) selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle until progressive disease (PD).
Drug: Selinexor
Selinexor 60mg
Other Name: KPT-330

Experimental: Phase 3 Double-blinded: Selinexor
Participants received a fixed blinding dose of 60 mg selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle until PD.
Drug: Selinexor
Selinexor 60mg
Other Name: KPT-330

Placebo Comparator: Phase 2 Double-blinded: Placebo Followed by Open Label- Selinexor
Participants received a fixed blinding dose of placebo matched to selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle until PD in double-blinded treatment period. Participants in the placebo group who had PD during the Phase 2 double-blinded treatment, will be elected to cross over to open-label selinexor.
Drug: Placebo
Other Name: sugar pill

Placebo Comparator: Phase 3 Double-blinded: Placebo Followed by Open Label- Selinexor
Participants received a fixed blinding dose of placebo matched to selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle until PD or development of unacceptable toxicity. Participants in the placebo group who had PD during the Phase 3 double-blinded treatment, will be elected to cross over to open-label selinexor.
Drug: Placebo
Other Name: sugar pill




Primary Outcome Measures :
  1. Phase 3 Double Blind: Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [ 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) ]
    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.

  2. Phase 3 Open Label: Progression-free Survival (PFS) as Per RECIST Version 1.1 [ 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) ]
    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.

  3. Phase 2 Double Blind: Progression-free Survival (PFS) as Per RECIST Version 1.1 [ 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) ]
    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.

  4. Phase 2 Open Label: Progression-free Survival (PFS) as Per RECIST Version 1.1 [ 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) ]
    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.


Secondary Outcome Measures :
  1. Phase 3 Double Blind: Overall Survival (OS) [ Time Frame: From date of randomization until death due to any cause, whichever occurred first (up to 70 months) ]
    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.

  2. Phase 3 Open Label: Overall Survival (OS) [ 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) ]
    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.

  3. Phase 2 Double Blind: Overall Survival (OS) [ Time Frame: From the date of randomization until death due to any cause, whichever occurred first (up to 70 months) ]
    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.

  4. Phase 2 Open Label: Overall Survival (OS) [ 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) ]
    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.

  5. Phase 3 Double Blind: Time-to-Progression (TTP) as Per RECIST Version 1.1 [ 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) ]
    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.

  6. Phase 3 Open Label: Time-to-Progression (TTP) as Per RECIST Version 1.1 [ 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) ]
    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.

  7. Phase 2 Double Blind: Time-to-Progression (TTP) as Per RECIST Version 1.1 [ 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) ]
    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.

  8. Phase 2 Open Label: Time-to-Progression (TTP) as Per RECIST Version 1.1 [ 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) ]
    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.

  9. Phase 3 Double Blind: Overall Response Rate (ORR) [ Time Frame: From date of randomization until the documentation of CR or PR (up to 70 months) ]
    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.

  10. Phase 3 Open Label: Overall Response Rate (ORR) [ Time Frame: From date of randomization in the Phase 3 open label period until the documentation of CR or PR (up to 70 months) ]
    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.

  11. Phase 2 Double Blind: Overall Response Rate (ORR) [ Time Frame: From date of randomization until the documentation of CR or PR (up to 70 months) ]
    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.

  12. Phase 2 Open Label: Overall Response Rate (ORR) [ Time Frame: From date of randomization in the Phase 2 open-label period until the documentation of CR or PR (up to 70 months) ]
    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.

  13. Phase 3 Double Blind: Duration of Response (DOR) [ Time Frame: From first occurrence of CR or PR until the first date of PD (up to 70 months) ]
    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.

  14. Phase 3 Double Blind: Progression-free Survival (PFS) as Per Investigator Assessment [ 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) ]
    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.

  15. Phase 3 Double Blind: Time to Next Treatment (TTNT) [ Time Frame: Time from randomization to the first new antineoplastic therapy or death due to any cause (up to 70 months) ]
    TTNT was defined as time since randomization until the first new antineoplastic therapy or death due to any cause, whichever occurs first.

  16. Phase 2 Double Blind: Time to Next Treatment (TTNT) [ Time Frame: Time from randomization to the first new antineoplastic therapy or death due to any cause (up to 70 months) ]
    TTNT was defined as time since randomization until the first new antineoplastic therapy or death due to any cause, whichever occurs first.

  17. Phase 3 Double Blind: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [ Time Frame: From start of study drug administration up to 70 months ]
    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.

  18. Phase 3 Open Label: Number of Participants With TEAEs and Serious TEAEs [ Time Frame: From start of study drug administration up to 70 months ]
    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.

  19. Phase 2 Double Blind: Number of Participants With TEAEs and Serious TEAEs [ Time Frame: From start of study drug administration up to 70 months ]
    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.

  20. Phase 2 Open Label: Number of Participants With TEAEs and Serious TEAEs [ Time Frame: From start of study drug administration up to 70 months ]
    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.

  21. Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) [ Time Frame: Baseline up to Day 1387 ]
    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).

  22. Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) [ Time Frame: Baseline up to Day 379 ]
    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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients ≥12 years of age
  2. Body surface area (BSA) ≥ 1.2 m2
  3. Histologic evidence of DDLS at any time prior to randomization AND current evidence of DDLS requiring treatment
  4. Must have measurable disease per RECIST v1.1 Response Criteria
  5. Radiologic evidence of disease progression within 6 months prior to randomization. If the patient received other intervening therapy after documented disease progression, further disease progression must be documented after the completion of the intervening therapy
  6. Must have had at least 2 prior lines of systemic therapy for liposarcoma (not to exceed 5 prior lines)
  7. If patient received any previous systemic therapy, the last dose must have been ≥ 21 days prior to randomization (or ≥ 5 half-lives of that drug, whichever is shorter) with all clinically significant therapy-related toxicities having resolved to ≤ Grade 1

Exclusion Criteria:

  1. Patients with pure well-differentiated liposarcoma (WDLS), myxoid/round cell or pleomorphic tumor histologic subtypes
  2. Known active hepatitis B (HepB), hepatitis C (HepC) or human immunodeficiency virus (HIV) infection
  3. Known central nervous system metastases

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02606461


Locations
Show Show 71 study locations
Sponsors and Collaborators
Karyopharm Therapeutics Inc
  Study Documents (Full-Text)

Documents provided by Karyopharm Therapeutics Inc:
Study Protocol  [PDF] May 21, 2020
Statistical Analysis Plan  [PDF] September 20, 2020

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Karyopharm Therapeutics Inc
ClinicalTrials.gov Identifier: NCT02606461    
Other Study ID Numbers: KCP-330-020
2015-003594-14 ( EudraCT Number )
First Posted: November 17, 2015    Key Record Dates
Results First Posted: December 7, 2021
Last Update Posted: January 23, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Karyopharm Therapeutics Inc:
Advanced unresectable dedifferentiated liposarcoma
selinexor
KCP-330
Karyopharm
Phase 2 / 3
dedifferentiated liposarcoma
Liposarcoma
Additional relevant MeSH terms:
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Liposarcoma
Neoplasms, Adipose Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma