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Selinexor in Advanced Liposarcoma (SEAL)

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ClinicalTrials.gov Identifier: NCT02606461
Recruitment Status : Active, not recruiting
First Posted : November 17, 2015
Results First Posted : December 7, 2021
Last Update Posted : December 7, 2021
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  • selinexor, will be withdrawn from further treatment and followed for survival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
Estimated Study Completion Date : December 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 cycle (42 days) up to 13 months 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 cycle (42 days) up to 38 months 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 cycle (42 days) up to 13 months 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 cycle (42 days) up to 14 months 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 56 months) ]
    Progression-free survival (PFS) was defined as the time from the 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 percent (%) increase in the 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 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 56 months) ]
    Progression-free survival (PFS) was defined as the time from 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 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 56 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 2 Double Blind: Overall Survival (OS) [ Time Frame: From the date of randomization until death due to any cause, whichever occurred first (up to 56 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.

  3. 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 56 months) ]
    TTP was defined as the time from date of randomization until determined progressive disease (PD) as per RECIST version. 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

  4. 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 56 months) ]
    TTP was defined as the time from date of randomization until determined progressive disease (PD) as per RECIST version. 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

  5. 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 56 Months ]
    Adverse events are 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. 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 are defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both Serious and non-serious TEAEs.

  6. Phase 2 Double Blind: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [ Time Frame: From start of study drug administration up to 56 Months ]
    Adverse events are 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. 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 are defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both Serious and non-serious TEAEs.

  7. Phase 3 Double Blind: Change From Baseline in Quality-of-Life Questionnaire 30 Item (QLQ-C30) [ Time Frame: Baseline up to Day 1135 ]
    The QLQ-C30 was a 30-item questionnaire developed to assess the quality of life of cancer patients. 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) scale. Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms. A negative change from baseline score indicates less functioning.



Information from the National Library of Medicine

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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 two (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 less than or equal 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
Investigators
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Study Director: Michael Kauffman, MD, Ph.D 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

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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: December 7, 2021
Last Verified: November 2021
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