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

Inclusion Criteria

• •1. Patients with histologically or cytologically confirmed solid malignancy or lymphoma that is metastatic or unresectable, and for which standard curative or palliative measures do not exist or are no longer effective.
• •For enrichment and dose expansion phase only:
• •Only patients with EBV-related tumors, including all nasopharyngeal carcinoma, as well as tumors known to be EBV-related which include (but are not limited to) gastric carcinoma (10-15%), lymphoma. These tumors (NPC excluded) should have:
• •i)EBER in situ hybridisation on paraffin samples/ circulating tumor cells; or ii)Elevated pre-treatment serum EBV viral titres
• •2. Patients who have had prior treatment with mTOR inhibitors and HDAC inhibitors will be allowed ONLY in the dose escalation phase
• •3. Age ≥ 21 years old.
• •4. Performance status of ≤ 2 (ECOG scale).
• •5. Target lesion on spiral CT or MRI scan must have at least one diameter \> 1 cm (on conventional CT scan the indicator lesion must have at least one diameter \> 2 cm) (for dose expansion).
• •6. Adequate bone marrow reserve: absolute granulocyte count \> 1 x 109/L, hemoglobin \> 8 g/dL and platelet count \>100,000/dL.
• •7. Adequate hepatic function (serum total bilirubin level \< 1.5 x ULN; alanine transaminase (ALT) and aspartate transaminase (AST) less than 3 times ULN.
• •8. Adequate renal function (creatinine \< 1.5 times ULN).
• •9. Normal ECG at baseline - with no significant conduction abnormalities and a QTc ≤ 450.
• •10. Left Ventricular Ejection Fraction ≥ 50% as assessed by MUGA scan or echocardiography at screening.
• •11. No concurrent use of investigational antineoplastic therapy.
• •12. No medical problems severe enough to prevent compliance with the study requirements
• •13. Negative pregnancy test (urinary β-HCG) at screening (applicable to women of child bearing potential who are sexually active).
• •14. Subjects must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.