Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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 evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04897880
Recruitment Status : Recruiting
First Posted : May 24, 2021
Last Update Posted : August 23, 2021
Sponsor:
Collaborators:
National Health and Medical Research Council, Australia
Secura Bio, Inc.
Information provided by (Responsible Party):
Australian & New Zealand Children's Haematology/Oncology Group

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.

Condition or disease Intervention/treatment Phase
Rhabdoid Tumor Atypical Teratoid/Rhabdoid Tumor Malignant Rhabdoid Tumor Recurrent Brain Tumor, Childhood Drug: Panobinostat Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 9, 2019
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2025


Arm Intervention/treatment
Experimental: Osteosarcoma [arm closed] Drug: Panobinostat
Panobinostat capsules, 10mg, starting at a de-escalated dose of 8mg/m2 per day
Other Name: Farydak®

Experimental: Malignant Rhabdoid Tumor/Atypical Teratoid Rhabdoid Tumor Drug: Panobinostat
Panobinostat capsules, 10mg, starting at a de-escalated dose of 8mg/m2 per day
Other Name: Farydak®

Experimental: Neuroblastoma [arm closed] Drug: Panobinostat
Panobinostat capsules, 10mg, starting at a de-escalated dose of 8mg/m2 per day
Other Name: Farydak®




Primary Outcome Measures :
  1. 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 ]
  2. 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 Measures :
  1. 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 ]
  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. [ Time Frame: 2 years after completion of treatment ]
  3. Overall Survival calculated as the time from registration to date of death [ Time Frame: 2 years after completion of treatment ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 39 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04897880


Contacts
Layout table for location contacts
Contact: David M Ashley, MBBS (Hon), FRACP, PhD (919) 684-5301 pedsneuronc@duke.edu
Contact: Ashley Walter, RN, MSN (919) 684-5301 pedsneuronc@duke.edu

Locations
Layout table for location information
United States, North Carolina
The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Australia, New South Wales
John Hunter Children's Hospital Active, not recruiting
New Lambton, New South Wales, Australia, 2305
Sydney Children's Hospital Active, not recruiting
Randwick, New South Wales, Australia, 2031
The Children's Hospital at Westmead Active, not recruiting
Westmead, New South Wales, Australia, 2145
Australia, South Australia
Women's and Children's Hospital Active, not recruiting
North Adelaide, South Australia, Australia, 5006
Australia, Tasmania
Royal Hobart Hospital Active, not recruiting
Hobart, Tasmania, Australia, 7000
Australia, Victoria
Monash Children's Hospital Active, not recruiting
Clayton, Victoria, Australia, 3168
The Royal Children's Hospital Active, not recruiting
Parkville, Victoria, Australia, 3052
Australia, Western Australia
Perth Children's Hospital Active, not recruiting
Nedlands, Western Australia, Australia, 6009
New Zealand
Starship Children's Hospital Active, not recruiting
Grafton, Auckland, New Zealand, 1023
Christchurch Hospital Active, not recruiting
Christchurch, New Zealand, 8011
Sponsors and Collaborators
Australian & New Zealand Children's Haematology/Oncology Group
National Health and Medical Research Council, Australia
Secura Bio, Inc.
Layout table for additonal information
Responsible Party: Australian & New Zealand Children's Haematology/Oncology Group
ClinicalTrials.gov Identifier: NCT04897880    
Other Study ID Numbers: ACCT008/ASSG35
ACTRN12618000321246 ( Registry Identifier: Australian New Zealand Clinical Trials Registry )
First Posted: May 24, 2021    Key Record Dates
Last Update Posted: August 23, 2021
Last Verified: August 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Australian & New Zealand Children's Haematology/Oncology Group:
Rhabdoid Tumor
Atypical Teratoid/Rhabdoid Tumor
Malignant Rhabdoid Tumor
Recurrent Brain Tumor, Childhood
Ashley
Pro00107447
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Brain Neoplasms
Rhabdoid Tumor
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplasms, Complex and Mixed
Neoplasms by Histologic Type
Panobinostat
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action