Optimal Precision TherapIes to CustoMISE Care in Childhood and Adolescent Cancer

January 5, 2024 updated by: Australian & New Zealand Children's Haematology/Oncology Group
A companion platform trial to test novel targeted agents based on the patient's tumor profile.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

82

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
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
Experimental: Arm B Pimasertib
Drug: Pimasertib Pimasertib 28mg/m2 oral, twice daily, 28 day cycle, 26 cycles
Drug: Pimasertib
Pimasertib 28mg/m2 oral, twice daily, 28 day cycle, 26 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants treated with molecularly-targeted agents in each treatment arm.
Time Frame: 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.
5 Years
Recommended phase II dose for each treatment arm
Time Frame: 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.
3 Years
Objective Response Rate (ORR) for each treatment arm.
Time Frame: 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.
5 Years

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Australian & New Zealand Children's Haematology/Oncology Group

Collaborators

The Hospital for Sick Children
Kazia Therapeutics Limited
Day One Biopharmaceuticals, Inc.
Medical Research Future Fund
C17 Council
Children's Cancer Institute Australia (CCIA)

Investigators

  • Study Chair: David Ziegler, Prof, Sydney Children's Hospital - Australian Study Chair
  • Study Chair: Daniel Morgenstern, Dr, The Hospital for Sick Children - Canadian Study Chair

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2024

Primary Completion (Estimated)

December 1, 2030

Study Completion (Estimated)

December 1, 2035

Study Registration Dates

First Submitted

December 12, 2023

First Submitted That Met QC Criteria

January 5, 2024

First Posted (Actual)

January 17, 2024

Study Record Updates

Last Update Posted (Actual)

January 17, 2024

Last Update Submitted That Met QC Criteria

January 5, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OPTIMISE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Plan to Share IPD: Neither the complete nor any part of the results of the study carried out under this protocol, nor any of the information provided by the Sponsor for the purposes of performing the study, will be published or passed on to any third party without the consent of the Study Committee.

The pseudonymized data will be shared for transparency reasons in the context of publications and after publication with other physicians and scientists (national and international academia) to promote and accelerate research on causes and treatment development of oncological diseases.

Requests for access to pseudonymized patient data for other scientific purposes will be reviewed by the Study Committee. A positive statement of the respective ethic committee and a signed data protection commitment are requested. Results of scientific research based on the study data may be used for academic teaching, research and scientific publications or presentations at scientific meetings.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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