Selinexor in Advanced Liposarcoma
SEAL
A Phase 2-3, Multicenter, Randomized, Double-blind Study of Selinexor (KPT-330) Versus Placebo in Patients With Advanced Unresectable Dedifferentiated Liposarcoma (DDLS)
2 other identifiers
interventional
342
10 countries
71
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jan 2016
Longer than P75 for phase_2
71 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 13, 2015
CompletedFirst Posted
Study publicly available on registry
November 17, 2015
CompletedStudy Start
First participant enrolled
January 4, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 28, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
October 26, 2021
CompletedResults Posted
Study results publicly available
December 7, 2021
CompletedJanuary 23, 2023
January 1, 2023
4.8 years
October 13, 2015
November 8, 2021
January 5, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
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.
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.
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.
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.
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)
From date of randomization until death due to any cause, whichever occurred first (up to 70 months)
Phase 3 Open Label: Overall Survival (OS)
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)
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)
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
From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 70 months)
- +17 more secondary outcomes
Study Arms (4)
Phase 2 Double-blinded: Selinexor
EXPERIMENTALParticipants 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
EXPERIMENTALParticipants 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 COMPARATORParticipants 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 COMPARATORParticipants 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.
Interventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (71)
Cedars-Sinai Medical Center
Los Angeles, California, 90048, United States
University of California, Los Angeles
Los Angeles, California, 90095, United States
Sarcoma Oncology Center
Santa Monica, California, 90403, United States
Stanford University
Stanford, California, 94305, United States
University of Colorado-Denver
Denver, Colorado, 80202, United States
Yale Cancer Center
New Haven, Connecticut, 06520-8032, United States
Mayo Clinic
Jacksonville, Florida, 32224, United States
Northwestern Memorial Hospital
Chicago, Illinois, 60611, United States
Johns Hopkins
Baltimore, Maryland, 21231, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Mayo Clinic Rochester
Rochester, Minnesota, 55905, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Columbia University Medical Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Northwell Health Physicians Partners
New York, New York, 11042, United States
Duke Institute of Cancer
Durham, North Carolina, 27710, United States
James Cancer Center, Ohio State University
Columbus, Ohio, 43210-1240, United States
Oregon Health and Science
Portland, Oregon, 97239, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19106, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
University of Pittsburgh Medical Center (UPMC)
Pittsburgh, Pennsylvania, 15232, United States
Vanderbilt
Nashville, Tennessee, 37232, United States
MD Anderson
Houston, Texas, 77030, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
UZ Brussel
Brussels, 1090, Belgium
UCL Saint-Luc
Brussels, 1200, Belgium
UZ Gent
Ghent, 9000, Belgium
Cross Cancer Center - Alberta Health Services
Edmonton, Alberta, T6G1Z2, Canada
The Ottawa Hospital Cancer
Ottawa, Ontario, Canada
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
McGill University
Montreal, Quebec, H4A3J1, Canada
Institut Bergonie
Bordeaux, 33076, France
Oscar Lambret Center
Lille, 59020, France
Centre Leon Berard
Lyon, 96373, France
Timone University Hospital
Marseille, 13385, France
Institut Régional du Cancer de Montpellier (ICM)
Montpellier, 34298, France
CLCC Antoine Lacassagne
Nice, 06789, France
Institut Curie
Paris, 75248, France
Institut Claudius Regaud
Toulouse, 31059, France
Institut Gustave Roussy
Villejuif, 94110, France
Helios Hospital Berlin-Buch
Berlin, 13125, Germany
Technische Universitaet Dresden Med. Fakultaet Carl Gustav Carus Med. Klinik u. Poliklinik I
Dresden, 01307, Germany
National Center for Tumor Diseases, Univeristy Hospital Heidelberg
Heidelberg, 69120, Germany
University Hospital Mannheim
Mannheim, 68167, Germany
Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie Klinikum rechts der Isar der TU Muenchen
München, 81675, Germany
Soroka University Medical Center
Beersheba, 84101, Israel
Hadassah Medical Center
Jerusalem, 91120, Israel
Rabin Medical Center
Petah Tikva, 4941492, Israel
Sheba Medical Center
Ramat Gan, 52621, Israel
Tel Aviv Sourasky Medical
Tel Aviv, 64239, Israel
Assaf Harofe Medical Center
Ẕerifin, 7030000, Israel
Candiolo Cancer Institute
Candiolo, 10060, Italy
Istituto Nazionale dei Tumori, Milan
Milan, 20133, Italy
U.O.C. Oncologia Medica Oncology Department
Palermo, 90127, Italy
Policlinico Universitario Campus Biomedico
Roma, 00128, Italy
"Germans Trias Pujol" University Hospital
Badalona, 41013, Spain
Vall d´hebron University Hospital
Barcelona, 08035, Spain
Hospital Sant Pau Barcelona
Barcelona, 08041, Spain
Hospital ICO Bellvitge
Barcelona, 08908, Spain
Hospital Universitario Clínico San Carlos
Madrid, 28040, Spain
Hospital Universitario Virgen Del Rocio
Seville, 41013, Spain
Hospital La Fe Valencia
Valencia, 46026, Spain
Sahlgrenska Universitetssjukhuset
Gothenburg, 413 45, Sweden
Skane University Hospital
Lund, 221 85, Sweden
Onkologiska Kliniken
Stockholm, 171 76, Sweden
Cambridge University Hospitals NHS Foundation Trust
Cambridge, CB2 0QQ, United Kingdom
University College London Hospitals
London, NW1 2BU, United Kingdom
The Royal Marsden NHS Foundation Trust
London, SW3 6JJ, United Kingdom
The Christie
Manchester, M20 4BX, United Kingdom
Related Publications (1)
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.
PMID: 35394800DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Karyopharm Medical Information
- Organization
- Karyopharm Therapeutics Inc
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 13, 2015
First Posted
November 17, 2015
Study Start
January 4, 2016
Primary Completion
October 28, 2020
Study Completion
October 26, 2021
Last Updated
January 23, 2023
Results First Posted
December 7, 2021
Record last verified: 2023-01