NORTHA Phase II Study of Panobinostat in Pediatric, Adolescent and Young Adult Patients With Solid Tumors Including Osteosarcoma, Malignant Rhabdoid Tumor/Atypical Teratoid Rhabdoid Tumors and Neuroblastoma

This is an open label, phase II, multi-centre study evaluating the anti-tumor activity of continuous, low dose of panobinostat in patients with recurrent or refractory solid tumors stratified by primary histology into osteosarcoma, malignant rhabdoid tumor/atypical teratoid rhabdoid tumor (MRT/ATRT), and neuroblastoma. Patients will be stratified at study entry by tumor type into three strata: osteosarcoma, MRT/ATRT and neuroblastoma \[osteosarcoma and neuroblastoma arms are closed to enrolment\]. Patients will be enrolled onto the study following completion of their conventional therapy including chemotherapy and/or radiation treatment and completion of a three-week wash out period. Panobinostat will then be administered as a continuous oral dose (starting at a de-escalated dose of 8mg/m2 per day), for up to 12 courses, a total of 48 weeks. The minimum dose is 2mg/m2 per day. Dosing will follow a dose de-escalation or escalation scheme for each stratum which will be determined by biological effect of the drug (measured in patient peripheral blood samples) and levels of toxicity (measured by dose limiting toxicity and adverse events observed). Dose levels for subsequent enrolments in each strata will be based on the de-escalated or escalated dose in each cohort. The final dose per strata will be that which achieves significant biological effect with acceptable toxicity that is maintained for a 4 week period. Patients or their parents/guardians will be required to maintain a drug diary to monitor drug usage throughout the trial. Patients will be followed for up to 2 years from completion of study therapy.