Background: Selinexor is an oral Selective Inhibitor of Nuclear Export compound that
specifically blocks Chromosomal Region Maintenance protein 1.
Objective: To evaluate the safety and tolerability of escalating doses of selinexor plus 5-fluorouracil,
leucovorin and oxaliplatin (mFOLFOX6) in metastatic colorectal cancer (mCRC) patients.
Methods: In this multicenter phase I trial, mCRC patients, eligible for oxaliplatin-based treatment,
were enrolled to receive oral selinexor on days 1, 3, and 8 plus mFOLFOX6 every two weeks. Primary
endpoint was the maximum tolerated dose. Secondary endpoints were toxicity, overall response
rate, progression free survival, and overall survival.
Results: Overall, 10 patients were enrolled, who had prior treatment with oxaliplatin (6/10), irinotecan
(8/10), bevacizumab (6/10) or anti-EGFR therapy (5/10). Four consecutive patients received
40 mg selinexor plus mFOLFOX6. All four experienced dose-limiting toxicities and withdrew from
the study after a median of two cycles. Thus, this dose level was regarded as toxic and no further patients
were evaluated at this dose. Six patients were enrolled with 20 mg selinexor plus mFOLFOX6.
Despite better tolerability, four patients withdrew (patient wish) after the first cycle and only two patients
continued until disease progression. Most commonly reported treatment emergent adverse
events were nausea (80%), diarrhea (70%), vomiting (60%), fatigue (60%), anorexia (40%), and impaired
vision (40%). Due to the short treatment exposure, no relevant clinical activity was observed.
Conclusion: In patients with metastatic colorectal cancer, selinexor on this dose schedule plus
mFOLFOX6 was not tolerable. Other dosing schedules or combinations may be evaluated. Clinical
trial identifier NCT02384850.