Personalised azacitidine combination therapy using AI-guided drug selection and dosing

Optimizing and Personalising Azacitidine Combination Therapy for Treating Solid Tumours Using the Quadratic Phenotypic Optimization Platform (QPOP) and an Artificial Intelligence-based Platform (CURATE.AI)

This study tests whether AI tools can pick the best azacitidine drug combination and personalise dosing for adults with certain solid tumours using each person's biopsy sample.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 21 Years to 99 Years
• Sex: All
• Sponsor: National University Hospital, Singapore (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Singapore)
• Trial ID: NCT05381038 on ClinicalTrials.gov

What this trial studies

This pilot trial uses an ex vivo drug screen (QPOP) on a participant's tumour biopsy to identify promising azacitidine-based drug combinations from a pre-specified pool. For the combination selected by QPOP, CURATE.AI is then used to build an individualised dosing profile based on the participant's measured responses to a set of doses. The approach aims to optimise both which drugs are given and at what doses, rather than relying on standard maximum tolerated doses. The trial is conducted at a single centre and combines laboratory-driven selection with clinical dose-guidance in early phase 1–2 testing.

Who should consider this trial

Good fit: Adults aged 21 or older with ECOG performance status 0–2 who have breast or gastric cancer where docetaxel, paclitaxel or irinotecan is indicated, have adequate organ function, and have undergone a QPOP drug screen indicating potential benefit from combining azacitidine with a taxane or irinotecan.

Not a fit: Patients without an available tumour biopsy for ex vivo testing, with poor organ function or performance status above 2, or whose QPOP screen does not indicate azacitidine combination benefit are unlikely to gain from this approach.

Why it matters

Potential benefit: If successful, the approach could deliver more effective and less toxic personalised combination treatments by matching drug choice and dose to each patient's tumour response.

How similar studies have performed: Early-phase reports and case-series using CURATE.AI and ex vivo combination-selection methods have shown promising signals, but large-scale randomized evidence is still lacking.

Eligibility criteria

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 of ≤ 5 ULN if involvement of the liver.
   3. Calculated creatinine clearance ≥ 30 mL/min or creatinine \< 1.5 x ULN.
4. Diagnosed with breast or gastric cancer, where docetaxel, paclitaxel or irinotecan is indicated for palliative therapy.
5. Patients who have undergone QPOP drug screen (e.g. under QGAIN (2019/00924) or NGAIN trial (2021/00009) where the drug screen indicated potential benefit of combining azacitidine with taxane or irinotecan.
6. Patients must have raised response marker above upper limit of local laboratory normal (e.g. CEA and/or CA19-9, CA 15-3, CA 125, AFP, and methylation markers such as but not limited to DNMT).

Exclusion Criteria:

1. Patients who are lactating or pregnant.
2. Patients with clinically significant hypersensitivity to one or more of the selected regimen's constituent drug(s) (e.g. patients with clinically significant hypersensitivity to irinotecan may not be enrolled on azacitidine + irinotecan, but may be allowed on azacitidine + paclitaxel or azacitidine + docetaxel).
3. Contraindication to any of the required concomitant drugs or supportive treatments.
4. Any clinically significant medical disease or psychiatric condition that, in the co-investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.
5. Major surgery within 28 days prior to start of the treatment.
6. 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.
7. Patients who previously underwent chemotherapy treatment with either docetaxel, paclitaxel and/or irinotecan may still be able to enrol into treatment with the same drug in combination with azacitidine provided they fulfil all other criteria and approval is sought by PI and Sponsor (e.g. patients previously treated with paclitaxel and are enroling for treatment with paclitaxel + azacitidine).
8. Patients with clinical suspicion or diagnosis of Gilbert's syndrome will not be allowed to enrol with azacitidine + irinotecan, but may be allowed to enrol for treatment with azacitidine + docetaxel or azacitidine + paclitaxel provided they fulfil all other criteria.

Where this trial is running

Singapore

• National University Hospital — Singapore, Singapore (Recruiting)

Study contacts

• Principal investigator: Wei Peng Yong — National University Hospital, Singapore
• Study coordinator: Wei Peng Yong

Conditions Solid Tumor; Gastrointestinal Cancer; Breast Cancer; QPOP; Cancer; Artificial Intelligence; CURATE.AI; Chemotherapy