Selinexor in Advanced Liposarcoma

NCT ID: NCT02606461

Last Updated: 2023-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 342 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-04
• Study Completion Date: 2021-10-26

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• selinexor, will be withdrawn from further treatment and followed for survival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

Conditions

Dedifferentiated Liposarcoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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 (42-day) cycle until progressive disease (PD).

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

Selinexor 60mg

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 (42-day) cycle until PD.

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

Selinexor 60mg

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 (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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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 (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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Selinexor

Selinexor 60mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

KPT-330; sugar pill

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

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karyopharm Therapeutics Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Cedars-Sinai Medical Center

Los Angeles, California, United States

University of California, Los Angeles

Los Angeles, California, United States

Sarcoma Oncology Center

Santa Monica, California, United States

Stanford University

Stanford, California, United States

University of Colorado-Denver

Denver, Colorado, United States

Yale Cancer Center

New Haven, Connecticut, United States

Mayo Clinic

Jacksonville, Florida, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

Johns Hopkins

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Mayo Clinic Rochester

Rochester, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

Columbia University Medical Center

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Northwell Health Physicians Partners

New York, New York, United States

Duke Institute of Cancer

Durham, North Carolina, United States

James Cancer Center, Ohio State University

Columbus, Ohio, United States

Oregon Health and Science

Portland, Oregon, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center (UPMC)

Pittsburgh, Pennsylvania, United States

Vanderbilt

Nashville, Tennessee, United States

MD Anderson

Houston, Texas, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

UZ Brussel

Brussels, , Belgium

UCL Saint-Luc

Brussels, , Belgium

UZ Gent

Ghent, , Belgium

Cross Cancer Center - Alberta Health Services

Edmonton, Alberta, Canada

The Ottawa Hospital Cancer

Ottawa, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

McGill University

Montreal, Quebec, Canada

Institut Bergonie

Bordeaux, , France

Oscar Lambret Center

Lille, , France

Centre Leon Berard

Lyon, , France

Timone University Hospital

Marseille, , France

Institut Régional du Cancer de Montpellier (ICM)

Montpellier, , France

CLCC Antoine Lacassagne

Nice, , France

Institut Curie

Paris, , France

Institut Claudius Regaud

Toulouse, , France

Institut Gustave Roussy

Villejuif, , France

Helios Hospital Berlin-Buch

Berlin, , Germany

Technische Universitaet Dresden Med. Fakultaet Carl Gustav Carus Med. Klinik u. Poliklinik I

Dresden, , Germany

National Center for Tumor Diseases, Univeristy Hospital Heidelberg

Heidelberg, , Germany

University Hospital Mannheim

Mannheim, , Germany

Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie Klinikum rechts der Isar der TU Muenchen

München, , Germany

Soroka University Medical Center

Beersheba, , Israel

Hadassah Medical Center

Jerusalem, , Israel

Rabin Medical Center

Petah Tikva, , Israel

Sheba Medical Center

Ramat Gan, , Israel

Tel Aviv Sourasky Medical

Tel Aviv, , Israel

Assaf Harofe Medical Center

Ẕerifin, , Israel

Candiolo Cancer Institute

Candiolo, , Italy

Istituto Nazionale dei Tumori, Milan

Milan, , Italy

U.O.C. Oncologia Medica Oncology Department

Palermo, , Italy

Policlinico Universitario Campus Biomedico

Roma, , Italy

"Germans Trias Pujol" University Hospital

Badalona, , Spain

Vall d´hebron University Hospital

Barcelona, , Spain

Hospital Sant Pau Barcelona

Barcelona, , Spain

Hospital ICO Bellvitge

Barcelona, , Spain

Hospital Universitario Clínico San Carlos

Madrid, , Spain

Hospital Universitario Virgen Del Rocio

Seville, , Spain

Hospital La Fe Valencia

Valencia, , Spain

Sahlgrenska Universitetssjukhuset

Gothenburg, , Sweden

Skane University Hospital

Lund, , Sweden

Onkologiska Kliniken

Stockholm, , Sweden

Cambridge University Hospitals NHS Foundation Trust

Cambridge, , United Kingdom

University College London Hospitals

London, , United Kingdom

The Royal Marsden NHS Foundation Trust

London, , United Kingdom

The Christie

Manchester, , United Kingdom

Countries

United States; Belgium; Canada; France; Germany; Israel; Italy; Spain; Sweden; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 35394800 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-003594-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KCP-330-020

Identifier Type: -

Identifier Source: org_study_id