A Study of Panobinostat in Pediatric Patients With Solid Tumors Including MRT/ATRT

Brief Title

A Study of Panobinostat in Pediatric Patients With Solid Tumors Including MRT/ATRT

Official Title

A 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

Brief Summary

      This trial is evaluating the anti-tumor activity and side effects of panobinostat in treating
      patients with osteosarcoma, malignant rhabdoid tumor/atypical teratoid rhabdoid tumor
      (MRT/ATRT), and neuroblastoma.

Detailed Description

      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

      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.

Study Phase

Phase 2

Study Type


Primary Outcome

Efficacy as measured by Clinical Benefit Rate (percentage of patients with stable disease or better using MRI/CT imaging)

Secondary Outcome

 Clinical Benefit Rate: Percentage of patients with stable disease or better using functional imaging (MIBG or FDG-PET).


Rhabdoid Tumor



Study Arms / Comparison Groups

 Osteosarcoma [arm closed]


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

January 9, 2019

Completion Date

December 24, 2021

Primary Completion Date

December 24, 2021

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must be < 40 years of age.

          -  Patient must have been histologically diagnosed with osteosarcoma, neuroblastoma or
             MRT/ATRT at time of diagnosis or relapse. [osteosarcoma and neuroblastoma arms are
             closed to recruitment].

          -  Patient disease is refractory to conventional therapy, in the case of osteosarcoma,
             neuroblastoma and MRT/ATRT or there is an absence of effective conventional therapy
             available in the case of ATRT. Patients must have stable disease (SD) or better
             following treatment with salvage therapy.

          -  Karnofsky performance level greater than or equal to 60% for patients 16 years of age
             and greater, OR Lansky performance levels greater than or equal to 60% for patients
             less than 16 years of age.

          -  Life expectancy of greater than 8 weeks.

          -  Fully recovered from acute toxic effects of all prior chemotherapy, immunotherapy or
             radiotherapy prior to entering study.

          -  Patients with CNS tumours who are receiving dexamethasone are on a stable/decreasing
             dose for at least 1 week.

          -  Adequate BM function

          -  Adequate renal function

          -  Adequate liver function

          -  Adequate cardiac function

          -  Adequate pulmonary function

          -  Adequate CNS function - seizure free for at least 2 months

          -  Adequate serum calcium, magnesium and potassium concentrations

          -  If female and post-menarchal, pregnancy test must be negative.

          -  If of reproductive potential, have agreed to use effective contraceptive method.

          -  If female and lactating, have agreed not to breastfeed.

          -  Patient and/or their legal guardian have signed a written informed consent form.

        Exclusion Criteria:

          -  Have received myelosuppressive chemotherapy and/or biologic therapy within 3 weeks (4
             weeks if prior nitrosourea).

          -  Have received local palliative radiotherapy within 2 weeks.

          -  Have received craniospinal radiotherapy within 3 weeks.

          -  Have received greater than or equal to 50% radiation of the pelvis within 6 weeks.

          -  Have received other substantial BM radiation within 6 weeks.

          -  Have received growth factor(s) within 1 week.

          -  Are receiving enzyme inducing anticonvulsant therapy.

          -  Are receiving medications associated with prolongation of QTc interval

          -  Are receiving hydrochlorothiazide.

          -  Are receiving metronidazole and/or disulfiram

          -  Have uncontrolled sepsis.

          -  Have previously received panobinostat.

          -  Have symptoms of congestive heart failure, uncontrolled cardiac rhythm disturbance, or
             a QTc greater than or equal to 450msec.




N/A - 39 Years

Accepts Healthy Volunteers



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Location Countries


Location Countries


Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

Australian & New Zealand Children's Haematology/Oncology Group


 National Health and Medical Research Council, Australia

Study Sponsor

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Verification Date

June 2022