Personalised, Rational, Efficacy-driven Cancer Drug Dosing Via an Artificial Intelligence SystEm - CURATE.AI (PRECISE CURATE.AI Trial)
Trial ID: NCT04522284
Status: UNKNOWN
Study type: INTERVENTIONAL
Phase: PHASE1; PHASE2
Start date: 2020-08-20
Completion date: 2023-08-01
Sponsor: National University Hospital, Singapore
Collaborators: The N.1 Institute for Health (N.1)
Conditions: Solid Tumor
Interventions: CURATE.AI; Capecitabine; XELOX; XELIRI; Ibrutinib
Locations: National University Hospital; Ng Teng Fong General Hospital
Countries: Singapore; Singapore
Enrollment: 20
Age range: 21 Years - 99 Years
Sex: ALL

Summary:
In the current clinical context, drug dosing in oncology is dictated by toxicity. The optimal dosages of drugs in combinatory regimens for solid tumours are not clear, and the typical physician's decision on dose adjustment is a clinical judgement based on the degree of toxicity experienced by the patient. CURATE.AI - a small data, AI-derived technology platform - allows personalised guidance of an individual's dose modulations based only on that individual's data. Additionally, CURATE.AI is mechanism-independent, and dynamically adapts to changes experienced by the subject, providing dynamic dose optimisation throughout the duration of the subject's treatment. This study aims to demonstrate the feasibility of applying CURATE.AI in standard of care settings for treatment of solid tumours. An additional objective is to explore tumour markers in serial measurements at weekly frequency of probing, with modulated doses.

Eligibility criteria:
Inclusion Criteria:

1. General Inclusion Criteria

   1. Males and females ≥ 21 years of age.
   2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
   3. Patients must meet the following clinical laboratory criteria within 21 days of starting treatment:

      1. Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet ≥ 50,000/mm3
      2. Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN or ≤ 5 ULN if involvement of the liver.
      3. Calculated creatinine clearance ≥ 30mL/min or creatinine \< 1.5 x ULN

   Exclusion Criteria:
2. General Exclusion Criteria

   1. Patients who are lactating or pregnant.
   2. Major surgery within 28 days prior to start of the treatment.
   3. Active congestive heart failure (New York Heart Association \[NYHA\] Class III or IV), symptomatic ischaemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 4 months prior to informed consent obtained.
   4. Patients with clinically significant hypersensitivity to one or more of the selected regimen's constituent drug(s) (e.g. patient's with clinically significant hypersensitivity to oxaliplatin may not be enrolled on the XELOX regimen, but may be allowed on the XELIRI regimen).
   5. Contraindication to any of the required concomitant drugs or supportive treatments.
   6. Any clinically significant medical disease or psychiatric condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.
3. Specific Recruitment Criteria for Cohort 1: Capecitabine in solid tumours

i. Specific Inclusion Criteria

1. Metastatic solid tumours not for curative intent therapy;
2. Planned for treatment with the following chemotherapy regimens: XELOX, XELIRI or single agent capecitabine.
3. Patients must have raised tumour marker above upper limit of local laboratory normal (e.g. CEA, CA19-9).

ii. Specific Exclusion Criteria Nil

d. Specific Recruitment Criteria for Cohort 2: Ibrutinib in Waldenström macroglobulinaemia

i. Specific Inclusion Criteria

1. Waldenström macroglobulinaemia (either newly diagnosed or relapsed) as defined by the World Health Organisation 2016 diagnostic criteria.
2. Immunofixation confirms immunoglobulin M paraprotein and total IgM \> 2 x ULN.

ii. Specific Exclusion Criteria

1. Systemic anti-lymphoma therapy within 3 weeks of enrolment. Steroids at a dose equivalent of prednisolone 30mg per day are allowed provided this is discontinued 72 hours prior to commencement of drug dosing on trial.
2. Need to withhold rituximab in view of the risk of IgM flare (applies to patients treated with rituximab-based regimens).
3. Platelet transfusion within 7 days of screening.
4. Granulocyte colony stimulating factor within 7 days of screening.

Outcomes:
Percentage of participants in whom we successfully apply CURATE.AI profile.