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

NCT ID: NCT04897880

Last Updated: 2025-02-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-09
• Study Completion Date: 2024-05-08

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.

Conditions

Rhabdoid Tumor; Atypical Teratoid/Rhabdoid Tumor; Malignant Rhabdoid Tumor; Recurrent Brain Tumor, Childhood

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Osteosarcoma [arm closed]

Group Type: EXPERIMENTAL

Panobinostat

Intervention Type: DRUG

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

Malignant Rhabdoid Tumor/Atypical Teratoid Rhabdoid Tumor

Group Type: EXPERIMENTAL

Panobinostat

Intervention Type: DRUG

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

Neuroblastoma [arm closed]

Group Type: EXPERIMENTAL

Panobinostat

Intervention Type: DRUG

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

Interventions

Panobinostat

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

Intervention Type: DRUG

Other Intervention Names

Farydak®

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.

• Maximum Eligible Age: 39 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Health and Medical Research Council, Australia

OTHER

Sponsor Role: collaborator

Secura Bio, Inc.

INDUSTRY

Sponsor Role: collaborator

Australian & New Zealand Children's Haematology/Oncology Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

Durham, North Carolina, United States

John Hunter Children's Hospital

New Lambton, New South Wales, Australia

Sydney Children's Hospital

Randwick, New South Wales, Australia

The Children's Hospital at Westmead

Westmead, New South Wales, Australia

Women's and Children's Hospital

North Adelaide, South Australia, Australia

Royal Hobart Hospital

Hobart, Tasmania, Australia

Monash Children's Hospital

Clayton, Victoria, Australia

The Royal Children's Hospital

Parkville, Victoria, Australia

Perth Children's Hospital

Nedlands, Western Australia, Australia

Starship Children's Hospital

Grafton, Auckland, New Zealand

Christchurch Hospital

Christchurch, , New Zealand

Countries

United States; Australia; New Zealand

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ACTRN12618000321246

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACCT008/ASSG35

Identifier Type: -

Identifier Source: org_study_id