Optimal Precision TherapIes to CustoMISE Care in Childhood and Adolescent Cancer

Childhood Cancer Clinical Trial

Official title:

Optimal Precision TherapIes to CustoMISE Care in Childhood and Adolescent Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06208657
• Other study ID #: OPTIMISE
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: March 2024
• Est. completion date: December 2035

Study information

• Verified date: January 2024
• Source: Australian & New Zealand Children's Haematology/Oncology Group
• Contact: National Study Coordinator
• Phone: +61293821730
• Email: SCHN-OPTIMISE[@]health.nsw.gov.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 82
• Est. completion date: December 2035
• Est. primary completion date: December 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 21 Years

Eligibility

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.

Related Conditions & MeSH terms

• Childhood Brain Tumor
• Childhood Cancer
• Childhood Solid Tumor
• Neoplasms
• Recurrence
• Recurrent Cancer
• Refractory Cancer

Intervention

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

Locations

Country	Name	City	State
Australia	Women's and Children's Hospital	Adelaide	South Australia
Australia	Queensland Children's Hospital	Brisbane	Queensland
Australia	Monash Children's Hospital	Melbourne	Victoria
Australia	Royal Children's Hospital	Melbourne	Victoria
Australia	John Hunter Children's Hospital	Newcastle	New South Wales
Australia	Perth Children's Hospital	Perth	Western Australia
Australia	Sydney Children's Hospital, Randwick	Sydney	New South Wales
Australia	The Children's Hospital at Westmead	Sydney	New South Wales
Canada	CHU Sainte Justine	Montréal
Canada	The Hospital for Sick Children	Toronto
Canada	BC Children's Hospital	Vancouver

Sponsors (7)

Lead Sponsor	Collaborator
Australian & New Zealand Children's Haematology/Oncology Group	C17 Council, Children's Cancer Institute Australia (CCIA), Day One Biopharmaceuticals, Inc., Kazia Therapeutics Limited, Medical Research Future Fund, The Hospital for Sick Children

Countries where clinical trial is conducted

Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	5 Years
Primary	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.	3 Years
Primary	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.	5 Years
Secondary	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.	5 Years
Secondary	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.	5 Years
Secondary	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.	5 Years
Secondary	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.	5 Years