A Phase II Study of Panobinostat in Paediatric, Adolescent and Young Adult Patients with Solid Tumours Including Osteosarcoma, Malignant Rhabdoid Tumour/Atypical Teratoid Rhabdoid Tumours and Neuroblastoma.

Phase 2

Active, not recruiting

• Conditions: Osteosarcoma; Malignant Rhabdoid Tumour; Neuroblastoma; Atypical Teratoid/Rhabdoid Tumour (AT/RT); Cancer - Children's - Other; Cancer - Children's - Brain; Cancer - Bone

• Registration Number: ACTRN12618000321246
• Lead Sponsor: Australian and New Zealand Children’s Haematology and Oncology Group (ANZCHOG)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-03-05
• Last Update Posted: 27 February 2023

Recruitment & Eligibility

• Status: Active, not recruiting
• Sex: All
• Target Recruitment: 25

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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Efficacy as measured by Clinical Benefit Rate (percentage of patients with stable disease or better using MRI/CT imaging)[Every 2 months for 12 months after intervention commencement (primary timepoint is 4 months)<br>];Safety, as assessed by laboratory evaluations, electrocardiograms, physical examination, measurement of vital signs, performance status and body weight. Adverse events will be graded according to the NCI-CTCAE, version 4.0<br>[Weekly for 1 month and then monthly for 12 months after intervention commencement<br>]

Secondary Outcome Measures

Name	Time	Method
Clinical Benefit Rate: Percentage of patients with stable disease or better using functional imaging (MIBG or FDG-PET).[Every 2 months for 12 months after treatment commencement];Time to progression calculated as the time from registration to date of event defined as the first documented progression or death resulting from underlying cancer.[2 years after completion of treatment];Overall Survival calculated as the time from registration to date of death[2 years after completion of treatment]