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

Rhabdoid Tumor Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04897880
• Other study ID #: ACCT008/ASSG35
• Secondary ID: ACTRN12618000321
• Status: Terminated
• Phase: Phase 2
• Start date: January 9, 2019
• Est. completion date: December 24, 2021

Study information

• Verified date: June 2022
• Source: Australian & New Zealand Children's Haematology/Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: December 24, 2021
• Est. primary completion date: December 24, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 39 Years

Eligibility

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.

Related Conditions & MeSH terms

• Atypical Teratoid/Rhabdoid Tumor
• Brain Neoplasms
• Malignant Rhabdoid Tumor
• Neoplasms
• Recurrent Brain Tumor, Childhood
• Rhabdoid Tumor

Intervention

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

Locations

Country	Name	City	State
Australia	Monash Children's Hospital	Clayton	Victoria
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Perth Children's Hospital	Nedlands	Western Australia
Australia	John Hunter Children's Hospital	New Lambton	New South Wales
Australia	Women's and Children's Hospital	North Adelaide	South Australia
Australia	The Royal Children's Hospital	Parkville	Victoria
Australia	Sydney Children's Hospital	Randwick	New South Wales
Australia	The Children's Hospital at Westmead	Westmead	New South Wales
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Starship Children's Hospital	Grafton	Auckland
United States	The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center	Durham	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Australian & New Zealand Children's Haematology/Oncology Group	National Health and Medical Research Council, Australia, Secura Bio, Inc.

Countries where clinical trial is conducted

United States,  Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy as measured by Clinical Benefit Rate (percentage of patients with stable disease or better using MRI/CT imaging)		4 months after intervention commencement
Primary	Safety, as assessed by incidence of adverse events graded according to the NCI-CTCAE, version 4.0		1 week to 12 months after intervention commencement
Secondary	Clinical Benefit Rate: Percentage of patients with stable disease or better using functional imaging (MIBG or FDG-PET).		Every 2 months for 12 months after treatment commencement
Secondary	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.		2 years after completion of treatment
Secondary	Overall Survival calculated as the time from registration to date of death		2 years after completion of treatment