ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12618000321246

Ethics application status

Approved

Date submitted

21/02/2018

Date registered

5/03/2018

Date last updated

24/03/2021

Date data sharing statement initially provided

19/02/2019

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

Secondary ID [1]

ACCT008

Secondary ID [2]

ASSG35

Secondary ID [3]

CLBH589XAU13T

Universal Trial Number (UTN)

U1111-1208-4010

Trial acronym

NORTH

Linked study record

Phase I study: ACTRN12609000978268

Health condition

Health condition(s) or problem(s) studied:

Osteosarcoma

Malignant Rhabdoid Tumour

Neuroblastoma

Atypical Teratoid/Rhabdoid Tumour (AT/RT)

Condition category

Condition code

Cancer

Children's - Other

Cancer

Children's - Brain

Cancer

Bone

Intervention/exposure

Study type

Interventional

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]

Treatment: Drugs

Comparator / control treatment

No Control Group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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

Timepoint [1]

Every 2 months for 12 months after intervention commencement (primary timepoint is 4 months)

Primary outcome [2]

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]

Weekly for 1 month and then monthly for 12 months after intervention commencement

Secondary outcome [1]

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

Timepoint [1]

Every 2 months for 12 months after treatment commencement

Secondary outcome [2]

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]

2 years after completion of treatment

Secondary outcome [3]

Overall Survival calculated as the time from registration to date of death

Timepoint [3]

2 years after completion of treatment

Eligibility

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

Gender

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

Treatment

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

Phase 2

Type of endpoint(s)

Safety/efficacy

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

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

2/04/2018

Actual

9/01/2019

Date of last participant enrolment

Anticipated

1/08/2021

Actual

Date of last data collection

Anticipated

1/08/2023

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,QLD,SA,TAS,WA,VIC

Recruitment hospital [1]

The Royal Childrens Hospital - Parkville

Recruitment hospital [2]

Sydney Children's Hospital - Randwick

Recruitment hospital [3]

The Children's Hospital at Westmead - Westmead

Recruitment hospital [4]

Womens and Childrens Hospital - North Adelaide

Recruitment hospital [5]

John Hunter Children's Hospital - New Lambton

Recruitment hospital [6]

Monash Children’s Hospital - Clayton

Recruitment hospital [7]

The Royal Adelaide Hospital - Adelaide

Recruitment hospital [8]

Princess Alexandra Hospital - Woolloongabba

Recruitment hospital [9]

Queensland Children's Hospital - South Brisbane

Recruitment hospital [10]

Peter MacCallum Cancer Centre - Melbourne

Recruitment hospital [11]

The Chris O’Brien Lifehouse - Camperdown

Recruitment hospital [12]

Perth Children's Hospital - Nedlands

Recruitment hospital [13]

Royal Hobart Hospital - Hobart

Recruitment postcode(s) [1]

3052 - Parkville

Recruitment postcode(s) [2]

2031 - Randwick

Recruitment postcode(s) [3]

2145 - Westmead

Recruitment postcode(s) [4]

5006 - North Adelaide

Recruitment postcode(s) [5]

2305 - New Lambton

Recruitment postcode(s) [6]

3168 - Clayton

Recruitment postcode(s) [7]

5000 - Adelaide

Recruitment postcode(s) [8]

4102 - Woolloongabba

Recruitment postcode(s) [9]

4101 - South Brisbane

Recruitment postcode(s) [10]

3000 - Melbourne

Recruitment postcode(s) [11]

2050 - Camperdown

Recruitment postcode(s) [12]

6009 - Nedlands

Recruitment postcode(s) [13]

7000 - Hobart

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Auckland, Christchurch

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

NHMRC

Address [1]

16 Marcus Clarke St,
Canberra City,
ACT 2600

Country [1]

Australia

Primary sponsor type

Other Collaborative groups

Name

Australian and New Zealand Children’s Haematology and Oncology Group (ANZCHOG)

Address

27-31 Wright Street, Clayton VIC 3168

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Sydney Children’s Hospitals Network Human Research Ethics Committee

Ethics committee address [1]

Corner Hawkesbury Road and Hainsworth Street
Locked Bag 4001 Westmead NSW 2145 Sydney Australia
DX 8213 Parramatta

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

10/10/2017

Approval date [1]

22/01/2018

Ethics approval number [1]

HREC/17/SCHN/425

Ethics committee name [2]

Central Health and Disability Ethics Committee

Ethics committee address [2]

Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington 6011

Ethics committee country [2]

New Zealand

Date submitted for ethics approval [2]

05/07/2018

Approval date [2]

28/08/2018

Ethics approval number [2]

18/CEN/129

Summary

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

Contacts

Principal investigator

Name

Dr Jayesh Desai

Address

Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne, VIC, 3000
AUSTRALIA

Country

Australia

Phone

+613 8559 7379

Fax

Jayesh.Desai@petermac.org

Contact person for public queries

Name

Mrs Robyn Strong

Address

ANZCHOG
Hudson Institute of Medical Research
27-31 Wright St, Clayton 3168

Country

Australia

Phone

+613 8572 2684

Fax

+613 9902 4810

robyn.strong@hudson.org.au

Contact person for scientific queries

Name

Dr Jayesh Desai

Address

Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne, VIC, 3000
AUSTRALIA

Country

Australia

Phone

+61 3 8559 7379

Fax

Jayesh.Desai@petermac.org

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 other documents available

Summary results

No Results

Trial Review