Optimal Precision TherapIes to CustoMISE Care in Childhood and Adolescent Cancer

Overview

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.

Interventions

• Drug Paxalisib
  Paxalisib starting at 21mg/m2 oral, daily, 28 day cycle, 13 cycles.
• Drug Opdualag
  Opdualag, a fixed-dose combination of Nivolumab 480mg and Relatlimab 160mg, intravenous, on day 1, 28 day cycle, 26 cycles
• Drug Irinotecan (drug)
  Irinotecan starting at 50mg/m2/day, intravenous, on days 1-5, 28 day cycle, 13 cycles.
• Drug Temozolomide (TMZ)
  Temozolomide starting at 150mg/m2/day, oral, on days 1-5, 28 day cycle, 13 cycles.

Primary outcome measures

• Number of participants treated with molecularly-targeted agents in each treatment arm. [Time frame: 5 Years]
• Recommended phase II dose for each treatment arm [Time frame: 3 Years]
• Objective Response Rate (ORR) for each treatment arm. [Time frame: 5 Years]

Secondary outcome measures (4)

• Overall Clinical Benefit Rate (CBR) for each treatment arm [Time frame: 5 Years]
• Progression Free Survival (PFS) for each treatment arm. [Time frame: 5 Years]
• Incidence of treatment-emergent adverse events for each treatment arm. [Time frame: 5 Years]
• Maximum Concentration (Cmax) of molecularly-targeted agents for each treatment arm. [Time frame: 5 Years]

Eligibility criteria

Inclusion criteria

• 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.
• 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.

Exclusion criteria

• 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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Australia · 9 centers

• John Hunter Children's Hospital — Newcastle
• Sydney Children's Hospital, Randwick — Sydney
• The Children's Hospital at Westmead — Sydney
• Queensland Children's Hospital — Brisbane
• Women's and Children's Hospital — Adelaide
• Royal Hobart Hospital — Hobart
• Monash Children's Hospital — Melbourne
• The Royal Children's Hospital — Melbourne
• … and 1 more center

Canada · 5 centers

• Stollery Children's Hospital — Edmonton
• CHU Sainte Justine — Montreal
• Children's Hospital of Eastern Ontario — Ottawa
• The Hospital for Sick Children — Toronto
• BC Children's Hospital — Vancouver

Identifiers

NCT: NCT06208657 · OPTIMISE · ANZCHOG2204

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗