Selinexor in Advanced Liposarcoma (SEAL)

Karyopharm Therapeutics

Status and phase: Completed; Phase 3; Phase 2

Conditions: Dedifferentiated Liposarcoma

Treatments: Drug: Placebo; Drug: Selinexor

Study type: Interventional

Funder types: Industry

Identifiers

NCT02606461

KCP-330-020

2015-003594-14 (EudraCT Number)

Details and patient eligibility

About

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).

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• selinexor, will be withdrawn from further treatment and followed for survival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

Enrollment: 342 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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342 participants in 4 patient groups, including a placebo group

Phase 2 Double-blinded: Selinexor

Experimental group

Description:

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).

Treatment:

Drug: Selinexor

Phase 3 Double-blinded: Selinexor

Experimental group

Description:

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.

Treatment:

Drug: Selinexor

Phase 2 Double-blinded: Placebo Followed by Open Label- Selinexor

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Phase 3 Double-blinded: Placebo Followed by Open Label- Selinexor

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo