- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04897880
A Study of Panobinostat in Pediatric Patients With Solid Tumors Including MRT/ATRT (NORTH)
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 Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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New South Wales
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New Lambton, New South Wales, Australia, 2305
- John Hunter Children's Hospital
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Randwick, New South Wales, Australia, 2031
- Sydney Children's Hospital
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Westmead, New South Wales, Australia, 2145
- The Children's Hospital at Westmead
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South Australia
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North Adelaide, South Australia, Australia, 5006
- Women's and Children's Hospital
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Tasmania
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Hobart, Tasmania, Australia, 7000
- Royal Hobart Hospital
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Victoria
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Clayton, Victoria, Australia, 3168
- Monash Children's Hospital
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Parkville, Victoria, Australia, 3052
- The Royal Children's Hospital
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Western Australia
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Nedlands, Western Australia, Australia, 6009
- Perth Children's Hospital
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Christchurch, New Zealand, 8011
- Christchurch Hospital
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Auckland
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Grafton, Auckland, New Zealand, 1023
- Starship Children's Hospital
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North Carolina
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Durham, North Carolina, United States, 27710
- The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Osteosarcoma [arm closed]
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Panobinostat capsules, 10mg, starting at a de-escalated dose of 8mg/m2 per day
Other Names:
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EXPERIMENTAL: Malignant Rhabdoid Tumor/Atypical Teratoid Rhabdoid Tumor
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Panobinostat capsules, 10mg, starting at a de-escalated dose of 8mg/m2 per day
Other Names:
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EXPERIMENTAL: Neuroblastoma [arm closed]
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Panobinostat capsules, 10mg, starting at a de-escalated dose of 8mg/m2 per day
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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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
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4 months after intervention commencement
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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
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1 week to 12 months after intervention commencement
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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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
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Every 2 months for 12 months after treatment commencement
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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
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2 years after completion of treatment
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Overall Survival calculated as the time from registration to date of death
Time Frame: 2 years after completion of treatment
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2 years after completion of treatment
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neoplasms by Histologic Type
- Neoplasms by Site
- Central Nervous System Neoplasms
- Nervous System Neoplasms
- Neoplasms, Complex and Mixed
- Neoplasms
- Brain Neoplasms
- Rhabdoid Tumor
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Histone Deacetylase Inhibitors
- Panobinostat
Other Study ID Numbers
- ACCT008/ASSG35
- ACTRN12618000321246 (REGISTRY: Australian New Zealand Clinical Trials Registry)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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