None listed
Conditions
Brief summary
This a multicentre phase II clinical trial to establish if low dose continuous Panobinostat is effective and safe in patients with relapsed or refractory cancer. Who is it for? You may be eligible for this study if you are less than 40 years old and have relapsed or refractory osteosarcoma, rhabdoid tumour and/or neuroblastoma. Study details All participants will receive oral Panobinostat for up to 12 months after completing their conventional therapy. Participants will have physical examinations, blood tests, urine tests, ECGs and imaging, including MRI/CT, MIBG or FDG-PET (depending on tumour type). This study will test the effectiveness of this new drug in paediatric, adolescent and young adult patients in cases where treatment options are limited.
Interventions
This is an open label, phase II, multicentre study evaluating the anti-tumour activity of continuous, low dose of panobinostat in patients with refractory solid tumours stratified by primary histology into osteosarcoma, malignant rhabdoid tumour/atypical teratoid rhabdoid tumour (MRT/ATRT), and neuroblastoma.
Patients will be stratified at study entry by tumour type into 3 strata: osteosarcoma, neuroblastoma and MRT/ATRT.
Patients will be enrolled onto the study following completion of their
This is an open label, phase II, multicentre study evaluating the anti-tumour activity of continuous, low dose of panobinostat in patients with refractory solid tumours stratified by primary histology into osteosarcoma, malignant rhabdoid tumour/atypical teratoid rhabdoid tumour (MRT/ATRT), and neuroblastoma. Patients will be stratified at study entry by tumour type into 3 strata: osteosarcoma, neuroblastoma and MRT/ATRT. 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 daily oral dose (starting at 10mg/m2 per day), for up to a year. Minimum dose is 2mg/m2 per day, maximum dose is 16mg/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 event 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. Participants (or their parent/guardian) will be required to maintain a daily drug dosing form to monitor drug usage throughout the trial.
Sponsors
Australian and New Zealand Children’s Haematology and Oncology Group (ANZCHOG)
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
No minimum to 39 Years
Healthy volunteers
No
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.
Outcome results
None listed