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

Primary Purpose

Rhabdoid Tumor, Atypical Teratoid/Rhabdoid Tumor, Malignant Rhabdoid Tumor

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Panobinostat
Sponsored by
Australian & New Zealand Children's Haematology/Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rhabdoid Tumor focused on measuring Rhabdoid Tumor, Atypical Teratoid/Rhabdoid Tumor, Malignant Rhabdoid Tumor, Recurrent Brain Tumor, Childhood, Ashley, Pro00107447

Eligibility Criteria

undefined - 39 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center
  • John Hunter Children's Hospital
  • Sydney Children's Hospital
  • The Children's Hospital at Westmead
  • Women's and Children's Hospital
  • Royal Hobart Hospital
  • Monash Children's Hospital
  • The Royal Children's Hospital
  • Perth Children's Hospital
  • Starship Children's Hospital
  • Christchurch Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Osteosarcoma [arm closed]

Malignant Rhabdoid Tumor/Atypical Teratoid Rhabdoid Tumor

Neuroblastoma [arm closed]

Arm Description

Outcomes

Primary Outcome Measures

Efficacy as measured by Clinical Benefit Rate (percentage of patients with stable disease or better using MRI/CT imaging)
Safety, as assessed by incidence of adverse events graded according to the NCI-CTCAE, version 4.0

Secondary Outcome Measures

Clinical Benefit Rate: Percentage of patients with stable disease or better using functional imaging (MIBG or FDG-PET).
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.
Overall Survival calculated as the time from registration to date of death

Full Information

First Posted
May 6, 2021
Last Updated
June 5, 2022
Sponsor
Australian & New Zealand Children's Haematology/Oncology Group
Collaborators
National Health and Medical Research Council, Australia, Secura Bio, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04897880
Brief Title
A Study of Panobinostat in Pediatric Patients With Solid Tumors Including MRT/ATRT
Acronym
NORTH
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Terminated
Why Stopped
Drug supply
Study Start Date
January 9, 2019 (Actual)
Primary Completion Date
December 24, 2021 (Actual)
Study Completion Date
December 24, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Australian & New Zealand Children's Haematology/Oncology Group
Collaborators
National Health and Medical Research Council, Australia, Secura Bio, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rhabdoid Tumor, Atypical Teratoid/Rhabdoid Tumor, Malignant Rhabdoid Tumor, Recurrent Brain Tumor, Childhood
Keywords
Rhabdoid Tumor, Atypical Teratoid/Rhabdoid Tumor, Malignant Rhabdoid Tumor, Recurrent Brain Tumor, Childhood, Ashley, Pro00107447

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Osteosarcoma [arm closed]
Arm Type
Experimental
Arm Title
Malignant Rhabdoid Tumor/Atypical Teratoid Rhabdoid Tumor
Arm Type
Experimental
Arm Title
Neuroblastoma [arm closed]
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Panobinostat
Other Intervention Name(s)
Farydak®
Intervention Description
Panobinostat capsules, 10mg, starting at a de-escalated dose of 8mg/m2 per day
Primary Outcome Measure Information:
Title
Efficacy as measured by Clinical Benefit Rate (percentage of patients with stable disease or better using MRI/CT imaging)
Time Frame
4 months after intervention commencement
Title
Safety, as assessed by incidence of adverse events graded according to the NCI-CTCAE, version 4.0
Time Frame
1 week to 12 months after intervention commencement
Secondary Outcome Measure Information:
Title
Clinical Benefit Rate: Percentage of patients with stable disease or better using functional imaging (MIBG or FDG-PET).
Time Frame
Every 2 months for 12 months after treatment commencement
Title
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.
Time Frame
2 years after completion of treatment
Title
Overall Survival calculated as the time from registration to date of death
Time Frame
2 years after completion of treatment

10. Eligibility

Sex
All
Maximum Age & Unit of Time
39 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
John Hunter Children's Hospital
City
New Lambton
State/Province
New South Wales
ZIP/Postal Code
2305
Country
Australia
Facility Name
Sydney Children's Hospital
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
The Children's Hospital at Westmead
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Women's and Children's Hospital
City
North Adelaide
State/Province
South Australia
ZIP/Postal Code
5006
Country
Australia
Facility Name
Royal Hobart Hospital
City
Hobart
State/Province
Tasmania
ZIP/Postal Code
7000
Country
Australia
Facility Name
Monash Children's Hospital
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
The Royal Children's Hospital
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Perth Children's Hospital
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Starship Children's Hospital
City
Grafton
State/Province
Auckland
ZIP/Postal Code
1023
Country
New Zealand
Facility Name
Christchurch Hospital
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand

12. IPD Sharing Statement

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

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