NCT01341834

Safety and Tolerability Study of RAD001 and LBH589 in All Solid Tumors With Enrichment for EBV Driven Tumors

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

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 49 (actual)
• Sponsor: National Cancer Centre, Singapore · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is: 1. 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). 2. To determine the pharmacokinetic profile of RAD001 in combination with two schedules of LBH589. 3. 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.

Detailed description

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.

Conditions

• Nasopharyngeal Carcinoma, Lymphomas, Any EBV+ Solid Tumour

Interventions

Type	Name	Description
DRUG	LBH589 and RAD001	Dose escalation of LBH589 tablets (5 and 10 mg) and RAD001 tablets (2.5, 5 mg and 10mg)

Timeline

• Start date: 2010-03-01
• Primary completion: 2016-06-01
• Completion: 2018-12-01
• First posted: 2011-04-26
• Last updated: 2018-04-24

Locations

1 site across 1 country: Singapore