A phase 2-3, multicenter, Randomized, Double-Blind Study of selinexor (KPT-330) versus placebo in Patients with Advanced Unresectable Dedifferentiated Liposarcoma (DDLS)
Johns Hopkins Kimmel Cancer Center in Baltimore
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 WHO Response Criteria, or death due to any cause; up to approximately 30 months.
Inclusion Criteria:1.Patients equal to 12 years of age2.Body surface area (BSA) equal to 1.2 m23.Histologic evidence of DDLS at any time prior to randomization AND current evidence of DDLS requiring treatment4.Must have measurable disease by the bidimensional WHO Response Criteria5.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 therapy6.Must have had at least one (1) prior line of systemic therapy for liposarcoma (no maximum number)7.If patient received any previous systemic therapy, the last dose must have been equal to 21 days prior to randomization (or equal to 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 1Exclusion 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
In the Phase 2 portion of the study, approximately 50 patients will be randomized to selinexor (60 mg) or placebo at a 1:1 allocation ratio.In the Phase 3 portion of the study, approximately 195 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be unblinded and if receiving:•placebo, may cross over to open-label selinexor (60mg twice weekly)•selinexor, will be withdrawn from further treatment and followed for survivalStudy treatment will be given twice weekly on Day 1 and Day 3 during Weeks 1-6 of each six-week (42 day) cycle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 WHO 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
12/06/2019 05:03 AM