MCRN 005 – The BOSTON Trial
Karyopharm Therapeutics has turned to Canada to lead a global Phase III randomized clinical trial (NCT03110562) that will evaluate the efficacy and safety of selinexor (KPT-330), an oral Selective Inhibitor of Nuclear Export (SINE™) compound.
This pivotal trial is led by Dr. Nizar Bahlis from the Arnie Charbonneau Cancer Institute of the University of Calgary in Alberta. The study will compare the combination of selinexor, bortezomib (Velcade®) and dexamethasone (SVd) versus the combination bortezomib and dexamethasone (Vd) in patients with relapsed or refractory myeloma who have had 1-3 prior lines of therapy.
BOSTON was designed based on data from the ongoing Phase II (MCRN 002) STOMP trial that has shown encouraging response data in the SVd combination arm, compared to historical response rates with the retreatment of a proteasome inhibitor (such as bortezomib) and dexamethasone alone. The results also included patients who were refractory to proteasome inhibitors. According to data presented at the 2016 American Society of Hematology annual meeting, SVd is well tolerated and its toxicity is manageable and similar to selinexor or bortezomib alone (monotherapy). The results also confirmed that selinexor demonstrates synergistic effects when combined with bortezomib.
The first Canadian patient was dosed with this regimen June 7, 2017 and a total of 362 patients will be recruited over the course of the trial across North America, Australia and Europe.
The following centres are open for patient recruitment:
- Calgary – Tom Baker Cancer Centre
- Edmonton – Cross Cancer Institute
- Halifax – Queen Elizabeth II Health Sciences Centre
- Montreal – Maisonneuve-Rosemont Hospital
- Montreal – Royal Victoria Hospital/McGill University
- Quebec City – Pavillon Hôtel-Dieu de Québec
- Toronto – Princess Margaret Cancer Centre
- Saskatoon - Saskatoon Cancer Centre
- Vancouver – Vancouver General Hospital
How Selinexor Works
Selinexor binds with and inhibits the nuclear export protein XPO1 (also called CRM1), resulting in the accumulation of tumour suppressor protein inside cells. This leads to the reinitiation (and amplification) of the cell’s ability to suppress tumours, possibly by stimulating selective cell death (apoptosis) in cancer (myeloma) cells, generally sparing normal cells.