Dedifferentiated LiposarcomaPhase 2/3SEALNCT02606461
Selinexor in Advanced Liposarcoma
A Phase 2/3 study testing Selinexor in people with Dedifferentiated Liposarcoma, run by Karyopharm Therapeutics Inc at 71 sites in 10 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Dedifferentiated Liposarcoma
- What is being tested?
- Selinexor
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 342 participants
- Where
- 71 sitesin 10 countries
- Study dates
- 4 Jan 2016to 26 Oct 2021
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
71 sites in 10 countries.
71 sites in 10 countries
United States26 sites
University of Michigan
Ann Arbor, Michigan, 48109
Johns Hopkins
Baltimore, Maryland, 21231
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Northwestern Memorial Hospital
Chicago, Illinois, 60611
James Cancer Center, Ohio State University
Columbus, Ohio, 43210-1240
University of Colorado-Denver
Denver, Colorado, 80202
Duke Institute of Cancer
Durham, North Carolina, 27710
MD Anderson
Houston, Texas, 77030
Mayo Clinic
Jacksonville, Florida, 32224
Cedars-Sinai Medical Center
Los Angeles, California, 90048
University of California, Los Angeles
Los Angeles, California, 90095
Vanderbilt
Nashville, Tennessee, 37232
Yale Cancer Center
New Haven, Connecticut, 06520-8032
Columbia University Medical Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Northwell Health Physicians Partners
New York, New York, 11042
University of Pennsylvania
Philadelphia, Pennsylvania, 19106
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
University of Pittsburgh Medical Center (UPMC)
Pittsburgh, Pennsylvania, 15232
Oregon Health and Science
Portland, Oregon, 97239
Mayo Clinic Rochester
Rochester, Minnesota, 55905
Sarcoma Oncology Center
Santa Monica, California, 90403
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
Washington University School of Medicine
St Louis, Missouri, 63110
Stanford University
Stanford, California, 94305
France9 sites
Institut Bergonie
Bordeaux, 33076
Oscar Lambret Center
Lille, 59020
Centre Leon Berard
Lyon, 96373
Timone University Hospital
Marseille, 13385
Institut Régional du Cancer de Montpellier (ICM)
Montpellier, 34298
CLCC Antoine Lacassagne
Nice, 06789
Institut Curie
Paris, 75248
Institut Claudius Regaud
Toulouse, 31059
Institut Gustave Roussy
Villejuif, 94110
Spain7 sites
"Germans Trias Pujol" University Hospital
Badalona, 41013
Vall d´hebron University Hospital
Barcelona, 08035
Hospital Sant Pau Barcelona
Barcelona, 08041
Hospital ICO Bellvitge
Barcelona, 08908
Hospital Universitario Clínico San Carlos
Madrid, 28040
Hospital Universitario Virgen Del Rocio
Seville, 41013
Hospital La Fe Valencia
Valencia, 46026
Israel6 sites
Soroka University Medical Center
Beersheba, 84101
Hadassah Medical Center
Jerusalem, 91120
Rabin Medical Center
Petah Tikva, 4941492
Sheba Medical Center
Ramat Gan, 52621
Tel Aviv Sourasky Medical
Tel Aviv, 64239
Assaf Harofe Medical Center
Ẕerifin, 7030000
Germany5 sites
Helios Hospital Berlin-Buch
Berlin, 13125
Technische Universitaet Dresden Med. Fakultaet Carl Gustav Carus Med. Klinik u. Poliklinik I
Dresden, 01307
National Center for Tumor Diseases, Univeristy Hospital Heidelberg
Heidelberg, 69120
University Hospital Mannheim
Mannheim, 68167
Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie Klinikum rechts der Isar der TU Muenchen
München, 81675
Canada4 sites
Cross Cancer Center - Alberta Health Services
Edmonton, Alberta, T6G1Z2
McGill University
Montreal, Quebec, H4A3J1
The Ottawa Hospital Cancer
Ottawa, Ontario
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
Italy4 sites
Candiolo Cancer Institute
Candiolo, 10060
Istituto Nazionale dei Tumori, Milan
Milan, 20133
U.O.C. Oncologia Medica Oncology Department
Palermo, 90127
Policlinico Universitario Campus Biomedico
Roma, 00128
United Kingdom4 sites
Cambridge University Hospitals NHS Foundation Trust
Cambridge, CB2 0QQ
University College London Hospitals
London, NW1 2BU
The Royal Marsden NHS Foundation Trust
London, SW3 6JJ
The Christie
Manchester, M20 4BX
Belgium3 sites
UZ Brussel
Brussels, 1090
UCL Saint-Luc
Brussels, 1200
UZ Gent
Ghent, 9000
Sweden3 sites
Sahlgrenska Universitetssjukhuset
Gothenburg, 413 45
Skane University Hospital
Lund, 221 85
Onkologiska Kliniken
Stockholm, 171 76
About this study
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)
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).
Read the 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
- Conditions
- Dedifferentiated Liposarcoma
- Being tested
- Selinexor, Placebo
- Keywords
- Advanced unresectable dedifferentiated liposarcoma, selinexor, KCP-330, Karyopharm, Phase 2 / 3, dedifferentiated liposarcoma, Liposarcoma
- Medical subject headings
- Liposarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SelinexorDrug
Also called KPT-330
Selinexor 60mg
PlaceboDrug
Also called sugar pill
| Study group | Role | What they receive |
|---|---|---|
| Phase 2 Double-blinded: Selinexor | Experimental | 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). Receives: Drug: Selinexor |
| Phase 3 Double-blinded: Selinexor | Experimental | 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. Receives: Drug: Selinexor |
| Phase 2 Double-blinded: Placebo Followed by Open Label- Selinexor | Placebo comparator | 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. Receives: Drug: Placebo |
| Phase 3 Double-blinded: Placebo Followed by Open Label- Selinexor | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Secondary outcomes (22)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: Baseline up to Day 379
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2015 (estimated)
- Study start4 Jan 2016
- Primary completion28 Oct 2020
- Study completion26 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Dedifferentiated LiposarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 342 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karyopharm Therapeutics Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02606461
- Sponsor's protocol ID
- KCP-330-020
- Other IDs
- 2015-003594-14, 2015
- Acronym
- SEAL
- Status last verified
- Jan 2023
- First submitted
- 13 Oct 2015
- Last updated
- 23 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Gounder MM, Razak AA, Somaiah N, Chawla S, Martin-Broto J, Grignani G, Schuetze SM, Vincenzi B, Wagner AJ, Chmielowski B, Jones RL, Riedel RF, Stacchiotti S, Loggers ET, Ganjoo KN, Le Cesne A, Italiano A, Garcia Del Muro X, Burgess M, Piperno-Neumann S, Ryan C, Mulcahy MF, Forscher C, Penel N, Okuno S, Elias A, Hartner L, Philip T, Alcindor T, Kasper B, Reichardt P, Lapeire L, Blay JY, Chevreau C, Valverde Morales CM, Schwartz GK, Chen JL, Deshpande H, Davis EJ, Nicholas G, Groschel S, Hatcher H, Duffaud F, Herraez AC, Beveridge RD, Badalamenti G, Eriksson M, Meyer C, von Mehren M, Van Tine BA, Gotze K, Mazzeo F, Yakobson A, Zick A, Lee A, Gonzalez AE, Napolitano A, Dickson MA, Michel D, Meng C, Li L, Liu J, Ben-Shahar O, Van Domelen DR, Walker CJ, Chang H, Landesman Y, Shah JJ, Shacham S, Kauffman MG, Attia S. Selinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial. J Clin Oncol. 2022 Aug 1;40(22):2479-2490. doi: 10.1200/JCO.21.01829. Epub 2022 Apr 8.
PubMed 35394800
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02606461
- Acronym / sponsor ID
- SEAL / KCP-330-020
- Conditions
- Dedifferentiated Liposarcoma
- Keywords
- Advanced unresectable dedifferentiated liposarcoma, selinexor, KCP-330, Karyopharm, Phase 2 / 3, dedifferentiated liposarcoma, Liposarcoma
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 342 participants (actual)
- Lead sponsor
- Karyopharm Therapeutics IncIndustry (pharma, biotech, devices)
- Study start
- 4 Jan 2016 (actual)
- Primary completion
- 28 Oct 2020 (actual)
- Study completion
- 26 Oct 2021 (actual)
- First posted
- 17 Nov 2015 (estimated)
- Results
- Posted 7 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase 2 Double-blinded: Selinexor | Experimental | Drug: SelinexorParticipants 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). |
| Phase 3 Double-blinded: Selinexor | Experimental | Drug: SelinexorParticipants 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. |
| Phase 2 Double-blinded: Placebo Followed by Open Label- Selinexor | Placebo comparator | Drug: PlaceboParticipants 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. |
| Phase 3 Double-blinded: Placebo Followed by Open Label- Selinexor | Placebo comparator | Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SelinexorAlso: KPT-330Selinexor 60mg | Drug | Phase 2 Double-blinded: Selinexor, Phase 3 Double-blinded: Selinexor |
| PlaceboAlso: sugar pill | Drug | Phase 2 Double-blinded: Placebo Followed by Open Label- Selinexor, Phase 3 Double-blinded: Placebo Followed by Open Label- Selinexor |
Primary outcome
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.
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.
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.
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.
22 secondary outcomes
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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
Phase 3 Open Label: Number of Participants With TEAEs and 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
Time frame: From start of study drug administration up to 70 months
Phase 2 Open Label: Number of Participants With TEAEs and 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)
Time frame: Baseline up to Day 1387
Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30)
Time frame: Baseline up to Day 379
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35394800Gounder MM, Razak AA, Somaiah N, Chawla S, Martin-Broto J, Grignani G, Schuetze SM, Vincenzi B, Wagner AJ, Chmielowski B, Jones RL, Riedel RF, Stacchiotti S, Loggers ET, Ganjoo KN, Le Cesne A, Italiano A, Garcia Del Muro X, Burgess M, Piperno-Neumann S, Ryan C, Mulcahy MF, Forscher C, Penel N, Okuno S, Elias A, Hartner L, Philip T, Alcindor T, Kasper B, Reichardt P, Lapeire L, Blay JY, Chevreau C, Valverde Morales CM, Schwartz GK, Chen JL, Deshpande H, Davis EJ, Nicholas G, Groschel S, Hatcher H, Duffaud F, Herraez AC, Beveridge RD, Badalamenti G, Eriksson M, Meyer C, von Mehren M, Van Tine BA, Gotze K, Mazzeo F, Yakobson A, Zick A, Lee A, Gonzalez AE, Napolitano A, Dickson MA, Michel D, Meng C, Li L, Liu J, Ben-Shahar O, Van Domelen DR, Walker CJ, Chang H, Landesman Y, Shah JJ, Shacham S, Kauffman MG, Attia S. Selinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial. J Clin Oncol. 2022 Aug 1;40(22):2479-2490. doi: 10.1200/JCO.21.01829. Epub 2022 Apr 8.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
71 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Selinexor in people with Dedifferentiated Liposarcoma, run by Karyopharm Therapeutics Inc at 71 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 71 sites in United States, France, Spain, Israel, Germany and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02606461, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2023.