A companion platform trial to test novel targeted agents based on the patient's tumor profile.
Patients must be diagnosed with a solid tumor, CNS tumor or lymphoma that has progressed despite standard therapy, or for which no effective standard therapy exists.
Age <21 years at inclusion; patients 21 years and older may be included after approval by the Study Chair if they have a pediatric type recurrent/refractory malignancy.
Patients must be enrolled on a precision medicine study (i.e. PROFYLE, ZERO or equivalent as agreed with Study Chair).
Patients enrolled in a Phase I cohort must have either evaluable or measurable disease.
Patients with symptomatic central nervous system (CNS) primary or metastatic tumours who are neurologically unstable or require increasing doses of corticosteroids or local CNS-directed therapy to control their CNS disease. Patients on stable doses of corticosteroids for at least 7 days prior to receiving study drug may be included.
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, or malabsorption syndrome) - only for arms that include orally administered therapeutic agents.
Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality), unstable ischemia, congestive heart failure within 12 months of screening.
Known active viral hepatitis or human immunodeficiency virus (HIV) infection or any other uncontrolled infection.
Parallel
Paxalisib
DrugPaxalisib starting at 21mg/m2 oral, daily, 28 day cycle, 13 cycles.
Opdualag
DrugOpdualag, a fixed-dose combination of Nivolumab 480mg and Relatlimab 160mg, intravenous, on day 1, 28 day cycle, 26 cycles
Irinotecan (drug)
DrugIrinotecan starting at 50mg/m2/day, intravenous, on days 1-5, 28 day cycle, 13 cycles.
Temozolomide (TMZ)
DrugTemozolomide starting at 150mg/m2/day, oral, on days 1-5, 28 day cycle, 13 cycles.
Number of participants treated with molecularly-targeted agents in each treatment arm.
Number of CAYA participants (children, adolescents and young adults) with advanced solid tumours (including CNS tumors and non-Hodgkin lymphomas) where molecular sequencing data was used to allocate treatment arms of molecularly-targeted agents.
Recommended phase II dose for each treatment arm
Recommended phase II dose of a novel single agent or combination treatment in CAYA participants, determined by dose-limiting toxicities reported as per CTCAE V5.0.
Objective Response Rate (ORR) for each treatment arm.
ORR defined as complete response and partial response, as measured by RECIST, RAPNO, INRC or RECIL in CAYA participants treated with molecularly-targeted agents.
Overall Clinical Benefit Rate (CBR) for each treatment arm
CBR defined as complete response and partial response and stable disease, as measured by RECIST, RAPNO, INRC or RECIL in CAYA participants treated with molecularly-targeted agents.
Progression Free Survival (PFS) for each treatment arm.
PFS in CAYA participants from initiation of treatment with molecularly-targeted agents to the occurrence of disease progression, as measured by RECIST, RAPNO, INRC or RECIL, or death.
Incidence of treatment-emergent adverse events for each treatment arm.
Safety and tolerability of molecularly-targeted agents as measured by incidence of treatment-emergent adverse events reported as per CTCAE V5.0 in CAYA participants.
Maximum Concentration (Cmax) of molecularly-targeted agents for each treatment arm.
Cmax in plasma after the first dose of molecularly-targeted agents in CAYA participants.
Click on the lead sponsor to view all of their trials.
Australian & New Zealand Children's Haematology/Oncology Group
Lead sponsor
The Hospital for Sick Children
Collaborator
Medical Research Future Fund
Collaborator
Kazia Therapeutics Limited
Collaborator
C17 Council
Collaborator
Bristol-Myers Squibb
Collaborator
Stand Up To Cancer
Collaborator
