Phase II Single Agent Study of Selinexor (KPT-330) in Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC) and Prior Therapy with Abiraterone

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Investigator: Charles J. Ryan, MD
Sponsor: Karyopharm Therapeutics, Inc.

Location(s): United States

Description

Abiraterone acetate is now considered the standard of care for patients with metastatic castrate-resistant prostate cancer (mCRPC) in the pre-chemotherapy setting. Patients with primary or acquired abiraterone resistance typically have rapidly progressive, refractory disease for which limited treatment options are available. The development of new therapies in mCRPC requires a focus on patients with primary or acquired resistance to abiraterone. Patients with abiraterone-refractory mCRPC have a poor prognosis overall with median survival after progression of disease at approximately 19 months. While chemotherapy is a standard approach in this setting, it is refused by many patients and clinicians due to toxicity concerns.

Selinexor is a first in class Selective Inhibitor of Nuclear Export (SINE) that specifically blocks the karyopherin protein Exportin 1 (XPO1/Exportin 1). XPO1 is a key regulatory protein responsible for the nuclear export leading to functional inactivation of tumor suppressor proteins (TSPs) and is up-regulated 2-4 fold in all cancers studied to date. Selinexor, given orally, has demonstrated potent anti-cancer activity in animal models of prostate cancer including inhibition of PC3 driven bone metastasis.The goal of this trial is to evaluate the potential for a progression free survival benefit associated with Selinexor administration in patients with abiraterone-refractory mCRPC.

Single agent phase II open label study of Selinexor in patients with mCRPC with prior therapy with standard hormone ablation agents and abiraterone. A maximum of 54 evaluable patients will be accrued for this study, provided the early stopping criteria are not met.

The starting dose for all patients will be an oral dose of 65 mg/m2, given twice per week at least 48 hours apart. Tablets for Selinexor oral administration will be supplied in two (2) strengths: 10 and 25 mg of active ingredient per tablet. Dexamethasone will be coadministered at a dose of 2 mg twice daily on the day of dosing and the day after.

Patients will be followed for 30 days after completion of treatment or removal from study, or until death, whichever occurs first. Patients removed from study for unacceptable treatment related adverse event(s) will be followed until resolution or stabilization of all treatment related adverse events to Grade 2 or lower.