Optimal Precision TherapIes to CustoMISE Care in Childhood and Adolescent Cancer

Phase 1

Recruiting

• Conditions: Recurrent Cancer; Refractory Cancer; Childhood Cancer; Childhood Brain Tumor; Childhood Solid Tumor
• Interventions: Drug: Paxalisib, Irinotecan, Temozolomide

• Registration Number: NCT06208657
• Lead Sponsor: Australian & New Zealand Children's Haematology/Oncology Group

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2023-12-12
• Study First Submitted QC: 2024-01-05
• Study First Posted: 2024-01-17
• Study Start: 2024-07-10
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-19
• Last Update Posted: 2025-02-21
• Primary Completion: 2030-12
• Study Completion: 2035-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 82

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A Paxalisib	Paxalisib, Irinotecan, Temozolomide	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

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) for each treatment arm.	5 Years	ORR defined as complete response and partial response, as measured by RECIST, RAPNO, INRC or RECIL in CAYA participants treated with molecularly-targeted agents.
Number of participants treated with molecularly-targeted agents in each treatment arm.	5 Years	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	3 Years	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.

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS) for each treatment arm.	5 Years	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.
Overall Clinical Benefit Rate (CBR) for each treatment arm	5 Years	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.
Maximum Concentration (Cmax) of molecularly-targeted agents for each treatment arm.	5 Years	Cmax in plasma after the first dose of molecularly-targeted agents in CAYA participants.
Incidence of treatment-emergent adverse events for each treatment arm.	5 Years	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.

Trial Locations

Locations (11)

John Hunter Children's Hospital; 🇦🇺 Newcastle, New South Wales, Australia

Sydney Children's Hospital, Randwick; 🇦🇺 Sydney, New South Wales, Australia

The Children's Hospital at Westmead; 🇦🇺 Sydney, New South Wales, Australia

Queensland Children's Hospital; 🇦🇺 Brisbane, Queensland, Australia

Women's and Children's Hospital; 🇦🇺 Adelaide, South Australia, Australia

Monash Children's Hospital; 🇦🇺 Melbourne, Victoria, Australia

Royal Children's Hospital; 🇦🇺 Melbourne, Victoria, Australia

Perth Children's Hospital; 🇦🇺 Perth, Washington, Australia

CHU Sainte Justine; 🇨🇦 Montréal, Canada

The Hospital for Sick Children; 🇨🇦 Toronto, Canada

BC Children's Hospital; 🇨🇦 Vancouver, Canada