The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR

Registration number
Ethics application status
Date submitted
Date registered
Date last updated
Date data sharing statement initially provided
Date results information initially provided
Type of registration
Prospectively registered

Titles & IDs
Public title
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.
Scientific title
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.
Secondary ID [1] 293872 0
Secondary ID [2] 303304 0
Secondary ID [3] 303305 0
Universal Trial Number (UTN)
Trial acronym
Linked study record
Phase I study: ACTRN12609000978268

Health condition
Health condition(s) or problem(s) studied:
Osteosarcoma 306338 0
Malignant Rhabdoid Tumour 306339 0
Neuroblastoma 306340 0
Atypical Teratoid/Rhabdoid Tumour (AT/RT) 306723 0
Condition category
Condition code
Cancer 305424 305424 0 0
Children's - Other
Cancer 305929 305929 0 0
Children's - Brain
Cancer 305930 305930 0 0

Study type
Description of intervention(s) / exposure
This is an open label, phase II, multicentre study evaluating the anti-tumour activity of continuous, low dose of panobinostat in patients with refractory solid tumours stratified by primary histology into osteosarcoma, malignant rhabdoid tumour/atypical teratoid rhabdoid tumour (MRT/ATRT), and neuroblastoma.

Patients will be stratified at study entry by tumour type into 3 strata: osteosarcoma, neuroblastoma and MRT/ATRT.

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 daily oral dose (starting at 10mg/m2 per day), for up to a year. Minimum dose is 2mg/m2 per day, maximum dose is 16mg/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 event 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.

Participants (or their parent/guardian) will be required to maintain a daily drug dosing form to monitor drug usage throughout the trial.
Intervention code [1] 300152 0
Treatment: Drugs
Comparator / control treatment
No Control Group
Control group

Primary outcome [1] 304573 0
Efficacy as measured by Clinical Benefit Rate (percentage of patients with stable disease or better using MRI/CT imaging)
Timepoint [1] 304573 0
Every 2 months for 12 months after intervention commencement (primary timepoint is 4 months)
Primary outcome [2] 304577 0
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
Timepoint [2] 304577 0
Weekly for 1 month and then monthly for 12 months after intervention commencement
Secondary outcome [1] 342438 0
Clinical Benefit Rate: Percentage of patients with stable disease or better using functional imaging (MIBG or FDG-PET).
Timepoint [1] 342438 0
Every 2 months for 12 months after treatment commencement
Secondary outcome [2] 342447 0
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.
Timepoint [2] 342447 0
2 years after completion of treatment
Secondary outcome [3] 342448 0
Overall Survival calculated as the time from registration to date of death
Timepoint [3] 342448 0
2 years after completion of treatment

Key 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.
Minimum age
No limit
Maximum age
39 Years
Both males and females
Can healthy volunteers participate?
Key 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
Purpose of the study
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?

Intervention assignment
Single group
Other design features
Phase 2
Type of endpoint/s
Statistical methods / analysis
The target enrolment is 20 participants per strata: 1) Osteosarcoma, 2) Neuroblastoma and 3) MRT/ATRT.

The study will employ a Simon two-stage minimax design (Simon, et al , 1989). Stage 2 will proceed if disease stability at 4 months is observed in three or more of the first nine patients in that strata and less than 30% of patients experience a dose limiting toxicity at the final dose level.

The Clinical Benefit Rate (percentage of participants with stable disease or better) will be calculated with a 95% CI. Time to progression (TTP) will be calculated as the time from registration to date of event defined as the first documented progression or death resulting from underlying cancer. TTP and Overall Survival will be estimated by the Kaplan-Meier survival analysis.

Recruitment status
Active, not recruiting
Date of first participant enrolment
Date of last participant enrolment
Date of last data collection
Sample size
Accrual to date
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 9882 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [2] 9884 0
Sydney Children's Hospital - Randwick
Recruitment hospital [3] 9885 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [4] 9886 0
Womens and Childrens Hospital - North Adelaide
Recruitment hospital [5] 9887 0
John Hunter Children's Hospital - New Lambton
Recruitment hospital [6] 13194 0
Monash Children’s Hospital - Clayton
Recruitment hospital [7] 13195 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [8] 13196 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [9] 13197 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [10] 13198 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [11] 13199 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [12] 18523 0
Perth Children's Hospital - Nedlands
Recruitment hospital [13] 18524 0
Royal Hobart Hospital - Hobart
Recruitment postcode(s) [1] 18687 0
2031 - Randwick
Recruitment postcode(s) [2] 25754 0
2050 - Camperdown
Recruitment postcode(s) [3] 18688 0
2145 - Westmead
Recruitment postcode(s) [4] 18690 0
2305 - New Lambton
Recruitment postcode(s) [5] 25753 0
3000 - Melbourne
Recruitment postcode(s) [6] 18685 0
3052 - Parkville
Recruitment postcode(s) [7] 25749 0
3168 - Clayton
Recruitment postcode(s) [8] 25752 0
4101 - South Brisbane
Recruitment postcode(s) [9] 25751 0
4102 - Woolloongabba
Recruitment postcode(s) [10] 25750 0
5000 - Adelaide
Recruitment postcode(s) [11] 18689 0
5006 - North Adelaide
Recruitment postcode(s) [12] 32862 0
6009 - Nedlands
Recruitment postcode(s) [13] 32863 0
7000 - Hobart
Recruitment outside Australia
Country [1] 21290 0
New Zealand
State/province [1] 21290 0
Auckland, Christchurch
Country [2] 24667 0
United States of America
State/province [2] 24667 0
North Carolina

Funding & Sponsors
Funding source category [1] 298490 0
Government body
Name [1] 298490 0
Country [1] 298490 0
Primary sponsor type
Other Collaborative groups
Australian and New Zealand Children’s Haematology and Oncology Group (ANZCHOG)
27-31 Wright Street, Clayton VIC 3168
Secondary sponsor category [1] 297633 0
Name [1] 297633 0
Address [1] 297633 0
Country [1] 297633 0

Ethics approval
Ethics application status
Ethics committee name [1] 299477 0
Sydney Children’s Hospitals Network Human Research Ethics Committee
Ethics committee address [1] 299477 0
Corner Hawkesbury Road and Hainsworth Street
Locked Bag 4001 Westmead NSW 2145 Sydney Australia
DX 8213 Parramatta
Ethics committee country [1] 299477 0
Date submitted for ethics approval [1] 299477 0
Approval date [1] 299477 0
Ethics approval number [1] 299477 0
Ethics committee name [2] 302705 0
Central Health and Disability Ethics Committee
Ethics committee address [2] 302705 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington 6011
Ethics committee country [2] 302705 0
New Zealand
Date submitted for ethics approval [2] 302705 0
Approval date [2] 302705 0
Ethics approval number [2] 302705 0

Brief summary
This a multicentre phase II clinical trial to establish if low dose continuous Panobinostat is effective and safe in patients with relapsed or refractory cancer.

Who is it for?
You may be eligible for this study if you are less than 40 years old and have relapsed or refractory osteosarcoma, rhabdoid tumour and/or neuroblastoma.

Study details
All participants will receive oral Panobinostat for up to 12 months after completing their conventional therapy. Participants will have physical examinations, blood tests, urine tests, ECGs and imaging, including MRI/CT, MIBG or FDG-PET (depending on tumour type).

This study will test the effectiveness of this new drug in paediatric, adolescent and young adult patients in cases where treatment options are limited.
Trial website
Trial related presentations / publications
Public notes

Principal investigator
Name 80542 0
Dr Jayesh Desai
Address 80542 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne, VIC, 3000

Country 80542 0
Phone 80542 0
+613 8559 7379
Fax 80542 0
Email 80542 0
Contact person for public queries
Name 80543 0
Mrs Robyn Strong
Address 80543 0
Hudson Institute of Medical Research
27-31 Wright St, Clayton 3168
Country 80543 0
Phone 80543 0
+613 8572 2684
Fax 80543 0
+613 9902 4810
Email 80543 0
Contact person for scientific queries
Name 80544 0
Dr Jayesh Desai
Address 80544 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne, VIC, 3000
Country 80544 0
Phone 80544 0
+61 3 8559 7379
Fax 80544 0
Email 80544 0

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
Aggregate results will be made available publicly

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIAtypical Teratoid Rhabdoid Tumours Are Susceptible to Panobinostat-Mediated Differentiation Therapy2021