Clinical trial NCT02606461: Selinexor in Advanced Liposarcoma
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Dedifferentiated Liposarcoma
Keywords: Advanced unresectable dedifferentiated liposarcoma
selinexor
KCP-330
Karyopharm
Phase 2 / 3
dedifferentiated liposarcoma
Liposarcoma
Lead sponsor: Karyopharm Therapeutics Inc
Sponsor class: INDUSTRY
First posted: 2015-11-17
Enrollment: 342
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).

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* selinexor, will be withdrawn from further treatment and followed for survival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

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Phase 3 Double Blind: Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: 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)
measure: Phase 3 Open Label: Progression-free Survival (PFS) as Per RECIST Version 1.1
timeFrame: 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)
measure: Phase 2 Double Blind: Progression-free Survival (PFS) as Per RECIST Version 1.1
timeFrame: From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 57 months)
measure: Phase 2 Open Label: Progression-free Survival (PFS) as Per RECIST Version 1.1
timeFrame: 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:
measure: Phase 3 Double Blind: Overall Survival (OS)
timeFrame: From date of randomization until death due to any cause, whichever occurred first (up to 70 months)
measure: Phase 3 Open Label: Overall Survival (OS)
timeFrame: From date of randomization in phase 3 open label period until death due to any cause, whichever occurred first (up to 70 months)
measure: Phase 2 Double Blind: Overall Survival (OS)
timeFrame: From the date of randomization until death due to any cause, whichever occurred first (up to 70 months)
measure: Phase 2 Open Label: Overall Survival (OS)
timeFrame: From date of randomization in the Phase 2 open-label period until death due to any cause, whichever occurred first (up to 70 months)
measure: Phase 3 Double Blind: Time-to-Progression (TTP) as Per RECIST Version 1.1
timeFrame: From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 70 months)
measure: Phase 3 Open Label: Time-to-Progression (TTP) as Per RECIST Version 1.1
timeFrame: 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)
measure: Phase 2 Double Blind: Time-to-Progression (TTP) as Per RECIST Version 1.1
timeFrame: From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 70 months)
measure: Phase 2 Open Label: Time-to-Progression (TTP) as Per RECIST Version 1.1
timeFrame: 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)
measure: Phase 3 Double Blind: Overall Response Rate (ORR)
timeFrame: From date of randomization until the documentation of CR or PR (up to 70 months)
measure: Phase 3 Open Label: Overall Response Rate (ORR)
timeFrame: From date of randomization in the Phase 3 open label period until the documentation of CR or PR (up to 70 months)
measure: Phase 2 Double Blind: Overall Response Rate (ORR)
timeFrame: From date of randomization until the documentation of CR or PR (up to 70 months)
measure: Phase 2 Open Label: Overall Response Rate (ORR)
timeFrame: From date of randomization in the Phase 2 open-label period until the documentation of CR or PR (up to 70 months)
measure: Phase 3 Double Blind: Duration of Response (DOR)
timeFrame: From first occurrence of CR or PR until the first date of PD (up to 70 months)
measure: Phase 3 Double Blind: Progression-free Survival (PFS) as Per Investigator Assessment
timeFrame: 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)
measure: Phase 3 Double Blind: Time to Next Treatment (TTNT)
timeFrame: Time from randomization to the first new antineoplastic therapy or death due to any cause (up to 70 months)
measure: Phase 2 Double Blind: Time to Next Treatment (TTNT)
timeFrame: Time from randomization to the first new antineoplastic therapy or death due to any cause (up to 70 months)
measure: Phase 3 Double Blind: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: From start of study drug administration up to 70 months
measure: Phase 3 Open Label: Number of Participants With TEAEs and Serious TEAEs
timeFrame: From start of study drug administration up to 70 months
measure: Phase 2 Double Blind: Number of Participants With TEAEs and Serious TEAEs
timeFrame: From start of study drug administration up to 70 months
measure: Phase 2 Open Label: Number of Participants With TEAEs and Serious TEAEs
timeFrame: From start of study drug administration up to 70 months
measure: Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30)
timeFrame: Baseline up to Day 1387
measure: Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30)
timeFrame: Baseline up to Day 379
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Denver
country: United States
facility: University of Colorado-Denver
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Northwell Health Physicians Partners
state: New York
city: Durham
country: United States
facility: Duke Institute of Cancer
state: North Carolina
city: Columbus
country: United States
facility: James Cancer Center, Ohio State University
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC)
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt
state: Tennessee
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Brussels
country: Belgium
facility: UZ Brussel
city: Brussels
country: Belgium
facility: UCL Saint-Luc
city: Ghent
country: Belgium
facility: UZ Gent
city: Edmonton
country: Canada
facility: Cross Cancer Center - Alberta Health Services
state: Alberta
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montréal
country: Canada
facility: McGill University
state: Quebec
city: Bordeaux,
country: France
facility: Institut Bergonie
city: Lille Cedex 307
country: France
facility: Oscar Lambret Center
city: Lyon Cedex
country: France
facility: Centre Leon Berard
city: Marseille Cedex 5
country: France
facility: Timone University Hospital
city: Montpellier
country: France
facility: Institut Régional du Cancer de Montpellier (ICM)
city: Nice
country: France
facility: CLCC Antoine Lacassagne
city: Paris
country: France
facility: Institut Curie
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Helios Hospital Berlin-Buch
city: Dresden
country: Germany
facility: Technische Universitaet Dresden Med. Fakultaet Carl Gustav Carus Med. Klinik u. Poliklinik I
city: Heidelberg
country: Germany
facility: National Center for Tumor Diseases, Univeristy Hospital Heidelberg
city: Mannheim
country: Germany
facility: University Hospital Mannheim
city: Muenchen
country: Germany
facility: Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie Klinikum rechts der Isar der TU Muenchen
city: Be'er Sheva
country: Israel
facility: Soroka University Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical
city: Zerifin
country: Israel
facility: Assaf Harofe Medical Center
city: Candiolo
country: Italy
facility: Candiolo Cancer Institute
city: Milano
country: Italy
facility: Istituto Nazionale dei Tumori, Milan
city: Palermo
country: Italy
facility: U.O.C. Oncologia Medica Oncology Department
city: Roma
country: Italy
facility: Policlinico Universitario Campus Biomedico
city: Badalona
country: Spain
facility: "Germans Trias Pujol" University Hospital
city: Barcelona
country: Spain
facility: Vall d´hebron University Hospital
city: Barcelona
country: Spain
facility: Hospital Sant Pau Barcelona
city: Barcelona
country: Spain
facility: Hospital ICO Bellvitge
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Valencia
country: Spain
facility: Hospital La Fe Valencia
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Lund
country: Sweden
facility: Skane University Hospital
city: Stockholm
country: Sweden
facility: Onkologiska Kliniken
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London Hospitals
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie
Study officials:
References:
citation: 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.