Clinical trial NCT06208657: Optimal Precision TherapIes to CustoMISE Care in Childhood and Adolescent Cancer
Official title: Optimal Precision TherapIes to CustoMISE Care in Childhood and Adolescent Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Childhood Cancer
Childhood Solid Tumor
Childhood Brain Tumor
Recurrent Cancer
Refractory Cancer
Keywords: children
basket trail
platform study
pediatric
solid tumor
paediatric
solid tumour
CNS tumor
CNS tumour
lymphoma
Lead sponsor: Australian & New Zealand Children's Haematology/Oncology Group
Sponsor class: OTHER
Collaborators: name: Children's Cancer Institute Australia (CCIA)
name: The Hospital for Sick Children
name: Medical Research Future Fund
name: Kazia Therapeutics Limited
name: C17 Council
First posted: 2024-01-17
Enrollment: 82
Sex: ALL
Minimum age (years): 0
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Number of participants treated with molecularly-targeted agents in each treatment arm.
timeFrame: 5 Years
measure: Recommended phase II dose for each treatment arm
timeFrame: 3 Years
measure: Objective Response Rate (ORR) for each treatment arm.
timeFrame: 5 Years
Secondary outcomes:
measure: Overall Clinical Benefit Rate (CBR) for each treatment arm
timeFrame: 5 Years
measure: Progression Free Survival (PFS) for each treatment arm.
timeFrame: 5 Years
measure: Incidence of treatment-emergent adverse events for each treatment arm.
timeFrame: 5 Years
measure: Maximum Concentration (Cmax) of molecularly-targeted agents for each treatment arm.
timeFrame: 5 Years
Other outcomes:
Locations:
city: Newcastle
country: Australia
facility: John Hunter Children's Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Sydney Children's Hospital, Randwick
state: New South Wales
city: Sydney
country: Australia
facility: The Children's Hospital at Westmead
state: New South Wales
city: Brisbane
country: Australia
facility: Queensland Children's Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Women's and Children's Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Monash Children's Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Perth
country: Australia
facility: Perth Children's Hospital
state: Washington
city: Montréal
country: Canada
facility: CHU Sainte Justine
city: Toronto
country: Canada
facility: The Hospital for Sick Children
city: Vancouver
country: Canada
facility: BC Children's Hospital
Study officials:
affiliation: Sydney Children's Hospital - Australian Study Chair
name: David Ziegler, Prof
role: STUDY_CHAIR
affiliation: The Hospital for Sick Children - Canadian Study Chair
name: Daniel Morgenstern, Dr
role: STUDY_CHAIR
References: