Childhood CancerPhase 1/2NCT06208657
Optimal Precision TherapIes to CustoMISE Care in Childhood and Adolescent Cancer
A Phase 1/2 study testing Paxalisib, Opdualag and Irinotecan (drug) in people with Childhood Cancer and Childhood Solid Tumor, run by Australian & New Zealand Children's Haematology/Oncology Group at 14 sites in 2 countries.
Trial summary
A companion platform trial to test novel targeted agents based on the patient's tumor profile. Read more about this study
- Who is it for?
- Ages 0 to 21 years
- Conditions the study is for
- Childhood Cancer, Childhood Solid Tumor, Childhood Brain Tumor
- What is being tested?
- Paxalisib, Opdualag and Irinotecan (drug)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 14 sitesin 2 countries
- Study dates
- 10 Jul 2024to Dec 2035
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
- 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.
- Patients must be enrolled on a precision medicine study (i.e. PROFYLE, ZERO or equivalent as agreed with Study Chair).
- Patients enrolled in a Phase I cohort must have either evaluable or measurable disease.
- 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.
- 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.
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- Performance status: Karnofsky performance status (for patients > 16 years of age) or Lansky play score (for patients ≤ 16 years of age) ≥ 50%.
- Life expectancy ≥ 6 weeks.
- 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.
- Adequate organ function.
- Able to comply with scheduled follow-up and with management of toxicity.
- Females of childbearing potential must have a negative serum or urine pregnancy test.
- Fertile males must agree to use adequate contraception during the study and following completion of treatment.
- Provide a signed and dated informed consent form.
Who cannot join
- Patients with symptomatic central nervous system (CNS) primary or metastatic tumours who are neurologically unstable or require increasing doses of corticosteroids or local CNS-directed therapy to control their CNS disease. Patients on stable doses of corticosteroids for at least 7 days prior to receiving study drug may be included.
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, or malabsorption syndrome) - only for arms that include orally administered therapeutic agents.
- Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality), unstable ischemia, congestive heart failure within 12 months of screening.
- Known active viral hepatitis or human immunodeficiency virus (HIV) infection or any other uncontrolled infection.
- Major surgery within 21 days of the first dose of investigational drug. Gastrostomy, ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumour biopsy and insertion of central venous access devices are not considered major surgery, but for these procedures, a 48-hour interval must be maintained before the first dose of the investigational drug is administered.
- Known hypersensitivity to any study drug or component of the formulation.
- Pregnant or nursing (lactating) females.
- 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 drug(s).
Trial locations and contacts
14 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
International Study Manager contact
14 sites in 2 countries
Australia9 sites, 9 recruiting
- Recruiting
Women's and Children's Hospital
Adelaide, South Australia
Amy Rudge, amy.rudge@sa.gov.au
- Recruiting
Queensland Children's Hospital
Brisbane, Queensland
Trang Le, trang.le2@health.qld.gov.au
- Recruiting
Royal Hobart Hospital
Hobart, Tasmania, 7000
David Nolan, david.nolan@ths.tas.gov.au
- Recruiting
Monash Children's Hospital
Melbourne, Victoria
Amanda St John, Amanda.StJohn@monashhealth.org
- Recruiting
The Royal Children's Hospital
Melbourne, Victoria
Kahlia Fox, clinicaltrialsmanager@rch.org.au
- Recruiting
John Hunter Children's Hospital
Newcastle, New South Wales
Rebecca Jensen, Rebecca.Jensen@health.nsw.gov.au
- Recruiting
Perth Children's Hospital
Perth, Western Australia
Jennifer McConnell, jennifer.mcconnell@health.wa.gov.au
- Recruiting
Sydney Children's Hospital, Randwick
Sydney, New South Wales
Sandra Montez, Sandra.Montez@health.nsw.gov.au
- Recruiting
The Children's Hospital at Westmead
Sydney, New South Wales
Annie Yeung, Annie.Yeung@health.nsw.gov.au
Canada5 sites, 5 recruiting
- Not yet recruiting
Stollery Children's Hospital
Edmonton
Farah Hassan, farah.hassan@albertahealthservices.ca
- Recruiting
CHU Sainte Justine
Montreal
Annie Lahaye, annie.lahaye.hsj@ssss.gouv.qc.ca
- Not yet recruiting
Children's Hospital of Eastern Ontario
Ottawa
Isabelle Laforest, ilaforest@cheo.on.ca
- Recruiting
The Hospital for Sick Children
Toronto
Aiman Siddiqi, aiman.siddiqi@sickkids.ca
- Recruiting
BC Children's Hospital
Vancouver
Peter Subrt, psubrt@bcchr.ca
About this study
A companion platform trial to test novel targeted agents based on the patient's tumor profile.
Read the 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.
- Conditions
- Childhood Cancer, Childhood Solid Tumor, Childhood Brain Tumor, Recurrent Cancer, Refractory Cancer
- Being tested
- Paxalisib, Opdualag, Irinotecan (drug), Temozolomide (TMZ)
- Keywords
- children, basket trial, platform study, pediatric, solid tumor, paediatric, solid tumour, CNS tumor, CNS tumour, lymphoma
- Medical subject headings
- Neoplasms, Recurrence, Central Nervous System Neoplasms, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaxalisibDrug
Paxalisib starting at 21mg/m2 oral, daily, 28 day cycle, 13 cycles.
OpdualagDrug
Opdualag, a fixed-dose combination of Nivolumab 480mg and Relatlimab 160mg, intravenous, on day 1, 28 day cycle, 26 cycles
Irinotecan (drug)Drug
Irinotecan starting at 50mg/m2/day, intravenous, on days 1-5, 28 day cycle, 13 cycles.
Temozolomide (TMZ)Drug
Temozolomide starting at 150mg/m2/day, oral, on days 1-5, 28 day cycle, 13 cycles.
| Study group | Role | What they receive |
|---|---|---|
| Arm A Paxalisib | Experimental | Drug: Irinotecan, Drug: Temozolomide, Drug: Paxalisib. Irinotecan starting at 50mg/m2/day, intravenous, on days 1-5, 28 day cycle, 13 cycles.
Temozolomide starting at 150mg/m2/day, oral, on days 1-5, 28 day cycle, 13 cycles.
Paxalisib starting at 21mg/m2 oral, daily, 28 day cycle, 13 cycles. Receives: Drug: Paxalisib; Drug: Irinotecan (drug); Drug: Temozolomide (TMZ) |
| Arm C Opdualag | Experimental | Drug: Opdualag, a fixed dose combination of Nivolumab and Relatlimab Opdualag, a fixed-dose combination of Nivolumab 480mg and Relatlimab 160mg, intravenous, on day 1, 28 day cycle, 26 cycles. Receives: Drug: Opdualag |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 5 Years
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.
Measured: 3 Years
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.
Measured: 5 Years
Secondary outcomes (4)
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.
Measured: 5 Years
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.
Measured: 5 Years
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.
Measured: 5 Years
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.
Measured: 5 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2024
- Study start10 Jul 2024
- Primary completionDec 2030 (estimated)
- Study completionDec 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Childhood CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Australian & New Zealand Children's Haematology/Oncology Group
- Sponsor type
- University, hospital or other
- Collaborators
- The Hospital for Sick Children, Medical Research Future Fund, Kazia Therapeutics Limited, C17 Council, Bristol-Myers Squibb, Stand Up To Cancer
- Responsible party
- Sponsor
- Investigators
- David Ziegler, Prof, Study chair, Sydney Children's Hospital - Australian Study ChairDaniel Morgenstern, Dr, Study chair, The Hospital for Sick Children - Canadian Study Chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06208657
- Sponsor's protocol ID
- OPTIMISE
- Other IDs
- ANZCHOG2204
- Status last verified
- Jan 2026
- First submitted
- 12 Dec 2023
- Last updated
- 28 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.