Personalised, Rational, Efficacy-Driven Cancer Drug Dosing via an Artificial Intelligence SystEm (PRECISE): A Protocol for the PRECISE CURATE.AI Pilot Clinical Trial

Abstract

Introduction: Oncologists have traditionally administered the maximum tolerated doses of drugs in chemotherapy. However, these toxicity-guided doses may lead to suboptimal efficacy. CURATE.AI is an indication-agnostic, mechanism-independent and efficacy-driven personalised dosing platform that may offer a more optimal solution. While CURATE.AI has already been applied in a variety of clinical settings, there are no prior randomised controlled trials (RCTs) on CURATE.AI-guided chemotherapy dosing for solid tumours. Therefore, we aim to assess the technical and logistical feasibility of a future RCT for CURATE.AI-guided solid tumour chemotherapy dosing. We will also collect exploratory data on efficacy and toxicity, which will inform RCT power calculations. Methods and analysis: This is an open-label, single-arm, two-centre, prospective pilot clinical trial, recruiting adults with metastatic solid tumours and raised baseline tumour marker levels who are planned for palliative-intent, capecitabine-based chemotherapy. As CURATE.AI is a small data platform, it will guide drug dosing for each participant based only on their own tumour marker levels and drug doses as input data. The primary outcome is the proportion of participants in whom CURATE.AI is successfully applied to provide efficacy-driven personalised dosing, as judged based on predefined considerations. Secondary outcomes include the timeliness of dose recommendations, participant and physician adherence to CURATE.AI-recommended doses, and the proportion of clinically significant dose changes. We aim to initially enrol 10 participants from two hospitals in Singapore, perform an interim analysis, and consider either cohort expansion or an RCT. Recruitment began in August 2020. This pilot clinical trial will provide key data for a future RCT of CURATE.AI-guided personalised dosing for precision oncology. Ethics and dissemination: The National Healthcare Group (NHG) Domain Specific Review Board has granted ethical approval for this study (DSRB 2020/00334). We will distribute our findings at scientific conferences and publish them in peer-reviewed journals. Trial registration number: NCT04522284.

Keywords: PRECISE CURATE.AI pilot clinical trial; artificial intelligence; chemotherapy; clinical decision support system; clinical trials; oncology; personalised medicine; precision medicine.

Conflict of interest statement

DH, ABl, and TK are inventors of pending and issued patents pertaining to artificial intelligence-based drug development and personalised medicine. DH and TK are shareholders of KYAN Therapeutics, which has licensed intellectual property pertaining to AI-based drug development. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Tan, Teo, Tadeo, Peng, Soh, Du, Luo, Bandla, Sundar, Ho, Kee and Blasiak.

Figures

Figure 1

Internal workflow for optimising combination therapy modulation with CURATE.AI for solid tumours, including scenarios that may lead to recalibration.

Figure 2

Overall trial schedule for 3 weeks long cycles. BI: Baseline investigations as per standard-of-care, including collection of demographics, medical/treatment history, vital signs, and conducting complete physical examination including performance status evaluation, blood tests [haematology, serum chemistries, tumour marker(s)] and imaging as clinically required. BD: Mandatory blood draws done every 3 weeks for the measurement of tumour marker(s) between Days 17–20 of each cycle, alongside serum chemistries and haematology as per standard-of-care. BD*: Additional blood draws for measurements of tumour markers(s), done once weekly (once between Days 4–7, and another between Days 11–14) performed solely for the purposes of the trial, and are necessary for cycles 1–2 of chemotherapy. Additional blood draws in subsequent cycles will be limited to one draw, if at all. CT*: Computed tomography scans performed approximately every two or three cycles as per standard-of-care. End of study: upon completion of all chemotherapy cycles, or at 12 months, whichever is earlier for each participant.