Safety and Tolerability Study of RAD001 and LBH589 in All Solid Tumors With Enrichment for EBV Driven Tumors
The purpose of this study is:
- To determine the optimal recommended phase II dose of two investigational study drugs, LBH589 and RAD001, given in combination in all solid tumors (With enrichment for EBV-Driven tumors).
- To determine the pharmacokinetic profile of RAD001 in combination with two schedules of LBH589.
- To assess the preliminary anti-tumor activity of RAD001 and LBH589.
This study will also be exploring the hypothesis that HDACi and mTOR inhibitors abrogate the effects of key viral proteins, and switch the virus from a latent proliferative phase to a lytic phase. Immunologic correlates will also be examined to ascertain T-cell subpopulations and expression of HLA class molecules. DCE-MRI will be subsequently employed in dose expansion to examine antiangiogenic effects.
|Nasopharyngeal Carcinoma, Lymphomas, Any EBV+ Solid Tumour||Drug: LBH589 and RAD001||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
|Official Title:||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|
- Safety and tolerability [ Time Frame: Weekly evaluation for the first 5 weeks (DLT period), and continued follow up until patients come off trial due to toxicity or progressive disease ]
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.
- Tumor response [ Time Frame: Every 2 months until disease progression or withdrawal from study - average of 6 - 12 months ]Tumor response will be evaluated at the end of every 8-weeks of treatment. Treatment will continue until one of the following occur; disease progression, unacceptable toxicity, death, or withdrawal from study. Best response (according to RECIST), as well as progression free survival will be reported.
|Actual Study Start Date:||March 2010|
|Estimated Study Completion Date:||December 2018|
|Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
LBH589-RAD001, single arm dose finding study
Drug: LBH589 and RAD001
Dose escalation of LBH589 tablets (5 and 10 mg) and RAD001 tablets (2.5, 5 mg and 10mg)
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01341834
|National Cancer Center Singapore|
|Singapore, Singapore, 169690|
|Principal Investigator:||Daniel Tan Shao Weng||National Cancer Center Singapore|