Optimal Precision TherapIes to CustoMISE Care in Childhood and Adolescent Cancer

Study Purpose

A companion platform trial to test novel targeted agents based on the patient's tumor profile.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	0 Years - 21 Years
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. 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. 2. 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. 3. Patients must be enrolled on a precision medicine study (i.e. PROFYLE, ZERO or equivalent as agreed with Study Chair. 4. Patients enrolled in a Phase I cohort must have either evaluable or measurable disease. 5. Patients enrolled in a Phase II cohort must have measurable disease. Evaluable and measurable disease are defined by standard imaging criteria for the patient's tumor type. 6. Disease evaluations, laboratory tests, and other clinical assessments that are considered standard of care may be undertaken at the patient's local oncology treatment centre with results transferred to study site for evaluation. 7. Performance status: Karnofsky performance status (for patients > 16 years of age) or Lansky play score (for patients ≤ 16 years of age) ≥ 50%. 8. Life expectancy ≥ 6 weeks. 9. Patients must have fully recovered from the acute toxic effects of all prior anticancer therapy and must meet the following minimum duration from prior anticancer-directed therapy prior to enrolment. 10. Adequate organ function. 11. Able to comply with scheduled follow-up and with management of toxicity. 12. Females of childbearing potential must have a negative serum or urine pregnancy test. 13. Fertile males must agree to use adequate contraception during the study and following completion of treatment. 14. Provide a signed and dated informed consent form.

Exclusion Criteria:

1. Patients with symptomatic CNS primary or metastatic tumors who are neurologically unstable or require increasing doses of corticosteroids or local CNS-directed therapy to control their CNS disease. 2. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs. 3. Clinically significant, uncontrolled heart disease. 4. Known active viral hepatitis or human immunodeficiency virus (HIV) infection or any other uncontrolled infection. 5. Presence of any ≥Grade 2 treatment-related toxicity. 6. Major surgery within 21 days of the first dose of investigational drug. 7. Known hypersensitivity to any study drug or component of the formulation. 8. Pregnant or nursing (lactating) females. 9. Any other concomitant serious medical condition or organ dysfunction that in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the investigational drugs.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06208657
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1/Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Australian & New Zealand Children's Haematology/Oncology Group
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	David Ziegler, ProfDaniel Morgenstern, Dr
Principal Investigator Affiliation	Sydney Children's Hospital - Australian Study ChairThe Hospital for Sick Children - Canadian Study Chair
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other, Industry
Overall Status	Not yet recruiting
Countries	Australia, Canada
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Childhood Cancer, Childhood Solid Tumor, Childhood Brain Tumor, Recurrent Cancer, Refractory Cancer

Additional Details

Both Australia (Zero Childhood Cancer) and Canada (PROFYLE) have developed precision oncology programs for the pediatric population through which samples from childhood/adolescent cancers undergo in depth genetic profiling. OPTIMISE is a companion platform trial, which will link patients to novel targeted agents based on their tumor profile. The trial will have multiple basket arms based on the most common genetically altered pathways the investigators have identified in these childhood cancers. Each arm of the trial will be histopathology agnostic and test a rational, novel combination therapy, to maximise potential clinical benefit.

Arms & Interventions

Arms

Experimental: Arm A Paxalisib

Drug: Irinotecan Drug: Temozolomide Drug: Paxalisib Irinotecan 50mg/m2/day, intravenous, on days 1-5, 28 day cycle, 13 cycles Temozolomide 150mg/m2/day, oral, on days 1-5, 28 day cycle, 13 cycles Paxalisib 21mg/m2 oral, daily, 28 day cycle, 13 cycles

Experimental: Arm B Pimasertib

Drug: Pimasertib Pimasertib 28mg/m2 oral, twice daily, 28 day cycle, 26 cycles

Interventions

Drug: - Paxalisib, Irinotecan, Temozolomide

Irinotecan 50mg/m2/day, intravenous, on days 1-5, 28 day cycle, 13 cycles Temozolomide 150mg/m2/day, oral, on days 1-5, 28 day cycle, 13 cycles Paxalisib 21mg/m2 oral, daily, 28 day cycle, 13 cycles

Drug: - Pimasertib

Pimasertib 28mg/m2 oral, twice daily, 28 day cycle, 26 cycles

Contact a Trial Team

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