None listed
Conditions
Brief summary
This is a study examining the use of a new anti-cancer drug called LBH589 in children with solid and central nervous system (CNS) tumours. It is only for children where a tumour does not respond to initial conventional therapies (refractory). At this time there is no standard treatment available for many children who have a refractory solid or CNS tumour. Faulty regulation of a cell protein (enzyme) in the body called a histone deacetylase (HDAC) is known to be present in many human cancers. It changes cell structures and weakens the activity of good cancer killing genes. LBH589 is a new investigational drug that can increase the activity of these good genes by reacting with the HDAC cell protein. It is hoped it will help kill the tumour. Research studies in the laboratory using LBH589 have shown a strong response against tumour cells. In addition LBH589 has shown anti-tumour activity in studies of adult cancer patients. LBH589 is now being investigated in clinical trials of solid and haematological tumours in adults. LBH589 is an investigational or experimental anti-cancer agent that has not yet been approved by either the Food and Drug Administration (FDA) or the Therapeutic Goods Administration (TGA). The drug has however been shown to be safe when given to adults on the schedule that will be used in this study. This study is assessing the dose levels that can be safely tolerated in children with solid and CNS tumours.
Interventions
This is an open label, Phase I, multicentre study evaluating the maximum tolerated dose of LBH589 (Panobinostat) in paediatric patients with refractory solid tumours including CNS tumours.
Patients will be separated into one of two groups depending on age and registered into escalating dose levels.
Group 1: patients < 12 years of age including infants
Group 2: patients >= 12 years - < 18 years
A course of treatment is 3 weeks and LBH589 will be administered intravenously (i.v.) weekly as a 30 mi
This is an open label, Phase I, multicentre study evaluating the maximum tolerated dose of LBH589 (Panobinostat) in paediatric patients with refractory solid tumours including CNS tumours. Patients will be separated into one of two groups depending on age and registered into escalating dose levels. Group 1: patients < 12 years of age including infants Group 2: patients >= 12 years - < 18 years A course of treatment is 3 weeks and LBH589 will be administered intravenously (i.v.) weekly as a 30 min infusion for week 1 and week 2 with week 3 for rest and evaluation. The starting dose is 15mg/m2 and inter-patient dose escalation or reductions will occur, in successive cohorts, at increments of 5mg/m2 with corresponding dose levels of 20mg/m2, 25mg/m2, 30 mg/m2 in cohorts of 3-6 patients until an MTD is reached. Patients may be recruited sequentially to the appropriate age range independent of recruitment to the other age range. Therefore these two recruitment groups will be run in parallel with an independent MTD dosing level being established for each group. Treatment can be continued for up to 17 courses or for up to 12 months.
Sponsors
Australian and New Zealand Children's Haematology and Oncology Group (ANZCHOG)
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
0 to 17 Years
Healthy volunteers
No
Inclusion criteria
* Patients must be < 18 years of age. * Patient must have been histologically diagnosed with refractory solid tumours (including CNS) at time of diagnosis or relapse. * Patient disease is refractory to conventional therapy or absence of conventional therapy available. * Karnosfsky performance level of >=60% for patients > 10yr of age, OR Lansky performance levels >=60% for patients <=10yr of age. * Life expectancy of >= 8 weeks. * Fully recovered from acute toxic effects of all prior chemotherapy, immunotherapy or radiotherapy prior to entering study. * Fully recovered (ie. No evidence of graft versus host disease) from stem cell transplant (SCT). * Patients with CNS tumours who are receiving dexamethasone are on a stable/decreasing dose for at least 1 week. * Adequate bone marrow (BM) function tested within 1 week of registration – peripheral blood absolute neutrophil count (ANC) > 1000/ul (or 1 x 109/mL); Platelet > 100 000/ul (or 100 x 109/mL); haemoglobin > 8gm/dL (or >80 g/L). * Adequate Renal function tested within 1 week of registration – age-adjusted normal serum creatinine or glomerular filtration rate (GFR) >70ml/min/1.73m2. * Adequate Liver function tested within 1 week of registration – total bilirubin <=1.5 x Institutional Upper Limit of Normal (IULN) for age, serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase(ALT)) <=5 x IULN for age, and albumin >= 2g/dL (20g/L). * Adequate Cardiac Function tested within 2 weeks of registration – shortening fraction of > 27% by echocardiogram OR ejection fraction of >= 50% by gated radionuclide study * Adequate Pulmonary function tested within 2 weeks of registration with no evidence of dyspnoea at rest, no exercise intolerance and pulse oximetry (SaO2) >94% * Adequate CNS function – seizure free for 2 months prior to study entry * Adequate serum calcium, magnesium and potassium concentrations tested within 1 week of registration – all must be >= Institutional Lower Limit of Normal (ILLN) for age with or without supplementation. * If female and postmenarchal, 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 guardians 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 (small port) within 2 weeks. * Have received craniospinal radiotherapy within 3 months. * Have received >50% radiation of the pelvis within 3 months. * Have received other substantial BM radiation within 6 weeks. * Have received allogeneic stem cell transplant within 6 months. * 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 while on study. * Are receiving Metronidazole and/or Disulfiram * Have uncontrolled Sepsis. * Have previously received LBH589. * Have symptoms of congestive heart failure, uncontrolled cardiac rhythm disturbance, or a QTc >= 450msec.
Outcome results
None listed