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

NCT04897880 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: ACCT008/ASSG35ACTRN12618000321246
• Study Type: interventional
• Target: 25
• Locations: 3 countries
• Sites: 11

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• Event free survival

  Estimated 2-year Event free survival (EFS). EFS is calculated as the time from study enrolment to first documented disease progression, relapse or second malignancy, or death from any cause.

  Up to 2 years after study enrolment

• Overall Survival

  Estimated 2-year Overall Survival (OS). OS is calculated as the time from study enrolment to death from any cause.

  Up to 2 years after study enrolment

• Safety: Adverse events summarised by grade and type

  Graded and defined by CTCAE Version 4

  From 1 week to 12 months after intervention commencement

Secondary Outcomes (1)

• Efficacy as measured by Clinical Benefit Rate

  At 6 and 12 months after intervention commencement

Other Outcomes (1)

• Comparison between trial participants and historical control data

  OS and EFS survival up to 2 years after study enrolment

Study Arms (3)

Osteosarcoma [arm closed]

EXPERIMENTAL

Drug: Panobinostat

Malignant Rhabdoid Tumor/Atypical Teratoid Rhabdoid Tumor

EXPERIMENTAL

Drug: Panobinostat

Neuroblastoma [arm closed]

EXPERIMENTAL

Drug: Panobinostat

Interventions

Panobinostat DRUG

Panobinostat capsules, 10mg, starting at a de-escalated dose of 8mg/m2 per day

Also known as: Farydak®

Malignant Rhabdoid Tumor/Atypical Teratoid Rhabdoid Tumor; Neuroblastoma [arm closed]; Osteosarcoma [arm closed]

Eligibility Criteria

• Age: Up to 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Australian & New Zealand Children's Haematology/Oncology Group: lead
• National Health and Medical Research Council, Australia: collaborator
• Secura Bio, Inc.: collaborator

Study Sites (11)

The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

John Hunter Children's Hospital

New Lambton, New South Wales, 2305, Australia

Location

Sydney Children's Hospital

Randwick, New South Wales, 2031, Australia

Location

The Children's Hospital at Westmead

Westmead, New South Wales, 2145, Australia

Location

Women's and Children's Hospital

North Adelaide, South Australia, 5006, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

Monash Children's Hospital

Clayton, Victoria, 3168, Australia

Location

The Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

Perth Children's Hospital

Nedlands, Western Australia, 6009, Australia

Location

Starship Children's Hospital

Grafton, Auckland, 1023, New Zealand

Location

Christchurch Hospital

Christchurch, 8011, New Zealand

Location

MeSH Terms

Conditions

Rhabdoid Tumor; Brain Neoplasms

Interventions

Panobinostat

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2021
• First Posted: May 24, 2021
• Study Start: January 9, 2019
• Primary Completion: May 8, 2024
• Study Completion: May 8, 2024
• Last Updated: February 24, 2025

Record last verified: 2025-02

Locations

AU (8); NZ (2); US (1)