A Safety and Tolerability Study of RAD001 (mTOR Inhibitor) in Combination With Two Dosing Schedules of LBH589B (Histone Deacetylase Inhibitor) in Solid Tumors/ Lymphomas With Enrichment for EBV-Driven Tumors
Dose escalation phase 1B of the study will evaluate the safety and tolerability of RAD001 in
combination with LBH589 in all solid tumors, lymphomas; and enriched for EBV driven tumors.
The phase 2 component will be a single arm, non-randomized study restricted to
nasopharyngeal carinoma only (endemic type).
A "3+3" dose escalation design will be adopted. Patients will start taking LBH589 three
times a week and will have a run in period of one week, followed by continous administration
of RAD001 from week 2. Pharmacokinetic assessments will be done on day 1 of LBH589
administration and day 1 of concurrent administration of LBH589 + RAD001. ON day 31, there
will be a one week drug holiday. This is done to explore the eliminaition kinetics from
steady state,as well as the durability of target modulation.
AEs of patients will be monitored closely. In the event of grade 3/4 toxicity, the cohort
will be expanded to 6. Dose escalation of LBH589/RAD001 may proceed until the maximum
tolerated dose (MTD)is reached. Once the MTD is established, an expasion cohort comprising
20 EBV driven tumors will open at two different LBH589 dose schedules.
Treatment will be continued until progression of disease, unacceptable toxcity, or
discontinuation criterion is met.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label
Safety and tolerability
Patients will be followed closely for toxicities in the first cycle where they would have weekly consultations visit. After the first cycle, consultation visits will be once every 2 weeks or once a month depending on how well the patient is tolerating the treatment. The following safety assesments will be done on every visit; Vital signs and physical examination Haematology and blood chemistry Cardiac monitoring EBV DNA titre (for patients with EBV Driven tumors recording of adverse events and serious adverse events.
Weekly evaluation for the first 5 weeks (DLT period), and continued follow up until patients come off trial due to toxicity or progressive disease
Daniel Tan Shao Weng
National Cancer Center Singapore
Singapore: Centralised Institutional Review Board B