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Completed

NCT Number: NCT02606461

Selinexor in Advanced Liposarcoma

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).

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Key information

Conditions

Dedifferentiated Liposarcoma Liposarcoma Neoplasms Neoplasms by Histologic Type Neoplasms, Adipose Tissue Neoplasms, Connective and Soft Tissue Sarcoma

Age range

12 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

UCL Saint-Luc, Brussels, Belgium

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About this study

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  • selinexor, will be withdrawn from further treatment and followed for survival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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients ≥12 years of age
  • Body surface area (BSA) ≥ 1.2 m2
  • Histologic evidence of DDLS at any time prior to randomization AND current evidence of DDLS requiring treatment
  • Must have measurable disease per RECIST v1.1 Response Criteria
  • 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
  • Must have had at least 2 prior lines of systemic therapy for liposarcoma (not to exceed 5 prior lines)
  • 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

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

Treatment and study plan

Selinexor

Drug

Selinexor 60mg

Other names: KPT-330

Placebo

Drug

Other names: sugar pill

Primary outcomes

  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 outcomes

  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).

Sponsors and collaborators

Lead sponsor

Karyopharm Therapeutics Inc

Industry

Registry information

Official study title

A Phase 2-3, Multicenter, Randomized, Double-blind Study of Selinexor (KPT-330) Versus Placebo in Patients With Advanced Unresectable Dedifferentiated Liposarcoma (DDLS)

Acronym: SEAL

Important dates

Study start
2016
Primary completion
2020
Study completion
2021
First posted
Nov 17, 2015
Registry last updated
Jan 23, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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