Optimal Precision TherapIes to CustoMISE Care in Childhood and Adolescent Cancer

Australian & New Zealand Children's Haematology/Oncology Group

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Recurrent Cancer; Childhood Solid Tumor; Refractory Cancer; Childhood Cancer; Childhood Brain Tumor

Treatments: Drug: Paxalisib, Irinotecan, Temozolomide; Drug: Pimasertib

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06208657

OPTIMISE

Details and patient eligibility

About

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

Full 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.

Enrollment: 82 estimated patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

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 design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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82 participants in 1 patient group

Arm A Paxalisib

Experimental group

Description:

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

Treatment:

Drug: Pimasertib

Drug: Paxalisib, Irinotecan, Temozolomide