Selinexor in Advanced Liposarcoma (SEAL)

• ClinicalTrials.gov Identifier: NCT02606461
• Recruitment Status: Recruiting
• First Posted: November 17, 2015
• Last Update Posted: September 6, 2019
• Sponsor: Karyopharm Therapeutics Inc
• Information provided by (Responsible Party): Karyopharm Therapeutics Inc

Study Description

Brief Summary:

This is a randomized, multicenter, double-blind, placebo-controlled, Phase 2-3 study of patients diagnosed with advanced unresectable dedifferentiated liposarcoma. Approximately 279 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 222 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• selinexor, will be withdrawn from further treatment and followed for survival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 AEs or failure to tolerate study treatment
• Patient withdrawal
• Patient discontinuation due to non-compliance

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 279 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)
• Study Start Date: December 2015
• Estimated Primary Completion Date: November 2019
• Estimated Study Completion Date: November 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Selinexor 60mg; Phase 2: 57 patients were randomized to selinexor or placebo in a 1:1allocation. Phase 3: Approximately 222 patients will be randomized to selinexor (~148 patients) or placebo (~74 patients) in a 2:1 allocation.	Drug: Selinexor; Selinexor 60mg; Other Name: KPT-330
Placebo Comparator: Placebo; Phase 2: Approximately 57 patients were randomized to selinexor or placebo in a 1:1 allocation. Phase 3: Approximately 222 patients will be randomized to selinexor (~148 patients) or placebo (~74 patients) in a 2:1 allocation.	Drug: Placebo; Other Name: sugar pill

Outcome Measures

Primary Outcome Measures :

1. Assess and compare Progression-free Survival (PFS) of patients with advanced unresectable DDLS treated with selinexor (60 milligrams [mg]) or placebo. [ Time Frame: From the date of randomization until the first date of disease progression, per RECIST v1.1 Response Criteria, or death due to any cause; up to approximately 30 months. ]

Eligibility Criteria

• 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 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

Contacts and Locations

Contacts

Contact: Michael Kauffman, M.D., Ph.D.; Mkauffman@karyopharm.com

Contact: Sharon Shacham, PhD; sshacham@karyopharm.com

  Show 71 Study Locations

Sponsors and Collaborators

Karyopharm Therapeutics Inc

Investigators

• Study Director: Michael Kauffman, MD, Ph.D; Karyopharm Therapeutics Inc

More Information

• Responsible Party: Karyopharm Therapeutics Inc
• ClinicalTrials.gov Identifier: NCT02606461 History of Changes
• Other Study ID Numbers: KCP-330-020; 2015-003594-14 ( EudraCT Number )
• First Posted: November 17, 2015
• Last Update Posted: September 6, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Keywords provided by Karyopharm Therapeutics Inc:

Advanced unresectable dedifferentiated liposarcoma; selinexor; KCP-330; Karyopharm; Phase 2 / 3; dedifferentiated liposarcoma; Liposarcoma

Additional relevant MeSH terms:

Liposarcoma; Neoplasms, Adipose Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma