PRECISE CURATE.AI Pilot Clinical Trial

NCT04522284 | Unknown Phase 1

• 1 other identifier: 2020/00334
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Solid Tumor

Keywords

Cancer; Artificial Intelligence; CURATE.AI; XELOX; Xeliri; Xeloda; Capecitabine; Chemotherapy; Phenotypic Personalized Medicine; Ibrutinib; Waldenström macroglobulinaemia

Outcome Measures

Primary Outcomes (1)

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

  CURATE.AI applicability: Percentage of participants in whom we successfully apply CURATE.AI profile. Based on percentages, outcomes will be classified as Green (\>70%) / Yellow (10-70%) / Red (\<10%). A decision on whether we "successfully apply" the CURATE.AI profile requires expert judgement and cannot be made based on a purely numerical process. The expert panel will consider the following factors with careful regard for the individual circumstances of each participant: 1. Error/variance (biological/analytical) is sufficiently small to allow accurate predictions 2. Profile can be generated sufficiently early for the participant to potentially benefit; 3. Dose-dependent relationship is observed; 4. Profile is actionable (i.e. fulfils the clinical investigator's pre-specified safety requirements); 5. Systemic changes in the participant which require profile recalibration are rare or readily assimilated into the CURATE.AI algorithm.

  Up to 12 months

Secondary Outcomes (5)

• Patient adherence

  Up to 12 months

• Timely delivery of CURATE.AI recommendations to the clinician

  Up to 12 months

• CURATE.AI relevance

  Up to 12 months

• Physician adherence

  Up to 12 months

• Clinically significant dose changes

  Up to 12 months

Other Outcomes (6)

• Percentage of trial participants with clinical progressive disease

  Up to 12 months

• Temporal variation in tumour marker level from baseline to trial conclusion.

  Up to 12 months

• Maximal reduction in tumour marker level measured as part of baseline investigations

  Up to 12 months

Study Arms (1)

CURATE.AI

EXPERIMENTAL

\- Cohort 1: Capecitabine in solid tumours. In this cohort, participants will receive the treatment in three-week cycles. Only the dose of capecitabine will be modulated with CURATE.AI, based on measurements of the tumour marker (CEA/CA19-9). CT scans for radiological assessment will be performed according to standard of care, usually after every 2 to 3 cycles of chemotherapy for Cohort 1 only. Cohort 2: Ibrutinib in Waldenström macroglobulinaemia In this cohort, participants will receive the treatment in four-week cycles. The total cumulative dose of Ibrutinib will be modulated with CURATE.AI, based on measurements of the tumour marker (IgM paraprotein).

Device: CURATE.AI; Drug: Capecitabine; Drug: XELOX; Drug: XELIRI; Drug: Ibrutinib

Interventions

CURATE.AI DEVICE

Efficacy and toxicity measurements at the end of each dosing cycle, together with an information on given drugs and their doses, and other patient data, will be used by CURATE.AI to recommend the dose of capecitabine and Ibrutinib for the next cycle. The clinical investigators will decide whether or not to administer or prescribe the dose recommendation from CURATE.AI.

CURATE.AI

Capecitabine DRUG

Treatment with the selected regimen will take up to a maximum duration of 12 months, in 3-week cycles. CURATE.AI dose recommendations will be generated before each chemotherapy cycle; fixed throughout the cycle; and within 1) the predetermined safety range (50% to 100% of dose used in standard of care treatment) and 2) subject-specific dosing range. Maximum total cumulative dose per cycle of capecitabine in the predetermined safety range is set at 100% of standard starting dose (i.e. , 1250mg/m2 twice daily for single agent capecitabine regimen). Minimum total cumulative dose per cycle of capecitabine in the predetermined safety range is set at 50% of the standard starting dose (i.e. 625mg/m2 twice daily for single agent capecitabine). Subject-specific dosing range may alter those numbers to suit the specific circumstances of the subject, thus giving the subject specific safe dosing range.

Also known as: XELODA

CURATE.AI

XELOX DRUG

Treatment with the selected regimen will take up to a maximum duration of 12 months, in 3-week cycles. CURATE.AI dose recommendations will be generated before each chemotherapy cycle; fixed throughout the cycle; and within 1) the predetermined safety range (50% to 100% of dose used in standard of care treatment) and 2) subject-specific dosing range. Maximum dose of capecitabine in the predetermined safety range is set at 100% of standard starting dose (i.e. 1000 mg/m2 twice daily for XELOX regimen). Minimum dose of capecitabine in the predetermined safety range is set at 50% of the standard starting dose (i.e. 500 mg/m2 twice daily for XELOX regimen). Subject-specific dosing range may alter those numbers to suit the specific circumstances of the subject, thus giving the subject specific safe dosing range. The doses of other drug in the XELOX regimen (oxaliplatin) will be held constant or adjusted at the clinical investigator's discretion, as per standard of care.

CURATE.AI

XELIRI DRUG

Treatment with the selected regimen will take up to a maximum duration of 12 months, in 3-week cycles. CURATE.AI dose recommendations will be generated before each chemotherapy cycle; fixed throughout the cycle; and within 1) the predetermined safety range (50% to 100% of dose used in standard of care treatment) and 2) subject-specific dosing range. Maximum dose of capecitabine in the predetermined safety range is set at 100% of standard starting dose (i.e. 1000 mg/m2 twice daily for XELIRI regimen). Minimum dose of capecitabine in the predetermined safety range is set at 50% of the standard starting dose (i.e. 500 mg/m2 twice daily for XELIRI regimen). Subject-specific dosing range may alter those numbers to suit the specific circumstances of the subject, thus giving the subject specific safe dosing range. The doses of other drug in the XELIRI regimen (irinotecan) will be held constant or adjusted at the clinical investigator's discretion, as per standard of care.

CURATE.AI

Ibrutinib DRUG

Treatment with the selected regimen will take up to a maximum duration of 12 months, in 4-week cycles. CURATE.AI dose recommendations will be generated before each chemotherapy cycle; fixed throughout the cycle; and within 1) the predetermined safety range (50% to 100% of dose used in standard of care treatment) and 2) subject-specific dosing range. Maximum total cumulative dose per cycle of Ibrutinib in the predetermined safety range is set at 100% of standard starting dose (i.e. 420 mg once daily for 4 weeks, which constitutes the total of 11760 mg per cycle). Minimum total cumulative dose per cycle of Ibrutinib in the predetermined safety range is set at 50% of the standard starting dose (i.e. 280 mg once daily on alternative days with 140 mg once daily, which constitutes the total of 5880 mg per cycle). The dosing range may be altered to suit the specific circumstances of the participant, thus giving the participant-specific safe dosing range.

CURATE.AI

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females ≥ 21 years of age.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
• Patients must meet the following clinical laboratory criteria within 21 days of starting treatment:
• Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet ≥ 50,000/mm3
• 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.
• Calculated creatinine clearance ≥ 30mL/min or creatinine \< 1.5 x ULN

You may not qualify if:

• Patients who are lactating or pregnant.
• Major surgery within 28 days prior to start of the treatment.
• 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.
• 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).
• Contraindication to any of the required concomitant drugs or supportive treatments.
• 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.
• Specific Recruitment Criteria for Cohort 1: Capecitabine in solid tumours
• Metastatic solid tumours not for curative intent therapy;
• Planned for treatment with the following chemotherapy regimens: XELOX, XELIRI or single agent capecitabine.
• Patients must have raised tumour marker above upper limit of local laboratory normal (e.g. CEA, CA19-9).
• d. Specific Recruitment Criteria for Cohort 2: Ibrutinib in Waldenström macroglobulinaemia
• Waldenström macroglobulinaemia (either newly diagnosed or relapsed) as defined by the World Health Organisation 2016 diagnostic criteria.
• Immunofixation confirms immunoglobulin M paraprotein and total IgM \> 2 x ULN.
• 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.
• Need to withhold rituximab in view of the risk of IgM flare (applies to patients treated with rituximab-based regimens).

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• The N.1 Institute for Health (N.1): collaborator

Study Sites (2)

National University Hospital

Singapore, 119074, Singapore

RECRUITING

Ng Teng Fong General Hospital

Singapore, Singapore

RECRUITING

Related Publications (6)

• Thummel KE, Lin YS. Sources of interindividual variability. Methods Mol Biol. 2014;1113:363-415. doi: 10.1007/978-1-62703-758-7_17.

  PMID: 24523121 RESULT

• Blasiak A, Khong J, Kee T. CURATE.AI: Optimizing Personalized Medicine with Artificial Intelligence. SLAS Technol. 2020 Apr;25(2):95-105. doi: 10.1177/2472630319890316. Epub 2019 Nov 26.

  PMID: 31771394 RESULT

• Rashid MBMA, Toh TB, Hooi L, Silva A, Zhang Y, Tan PF, Teh AL, Karnani N, Jha S, Ho CM, Chng WJ, Ho D, Chow EK. Optimizing drug combinations against multiple myeloma using a quadratic phenotypic optimization platform (QPOP). Sci Transl Med. 2018 Aug 8;10(453):eaan0941. doi: 10.1126/scitranslmed.aan0941.

  PMID: 30089632 RESULT

• Ho D. Artificial intelligence in cancer therapy. Science. 2020 Feb 28;367(6481):982-983. doi: 10.1126/science.aaz3023. No abstract available.

  PMID: 32108102 RESULT

• Zarrinpar A, Lee DK, Silva A, Datta N, Kee T, Eriksen C, Weigle K, Agopian V, Kaldas F, Farmer D, Wang SE, Busuttil R, Ho CM, Ho D. Individualizing liver transplant immunosuppression using a phenotypic personalized medicine platform. Sci Transl Med. 2016 Apr 6;8(333):333ra49. doi: 10.1126/scitranslmed.aac5954.

  PMID: 27053773 RESULT

• Tan BKJ, Teo CB, Tadeo X, Peng S, Soh HPL, Du SX, Luo VWY, Bandla A, Sundar R, Ho D, Kee TW, Blasiak A. Personalised, Rational, Efficacy-Driven Cancer Drug Dosing via an Artificial Intelligence SystEm (PRECISE): A Protocol for the PRECISE CURATE.AI Pilot Clinical Trial. Front Digit Health. 2021 Apr 12;3:635524. doi: 10.3389/fdgth.2021.635524. eCollection 2021.

  PMID: 34713106 DERIVED

MeSH Terms

Conditions

Neoplasms; Waldenstrom Macroglobulinemia

Interventions

Capecitabine; XELOX; ibrutinib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Raghav Sundar

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Raghav Sundar

CONTACT

+65 6779 5555; raghav_sundar@nuhs.edu.sg

Michelle Au

CONTACT

Michelle_YX_AU@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multi-centre, one-arm, prospective pilot study of participants diagnosed with either solid organ or haematological neoplasm.The participants will be enrolled for the duration of their treatment with the selected regimens, XELOX, XELIRI and single agent capecitabine regimens or single-agent ibrutinib . At 12-month mark, the decision on the patient engagement with the study will be made by the principal investigator in consultation with the study sponsors and treating physician.

Study Record Dates

• First Submitted: August 2, 2020
• First Posted: August 21, 2020
• Study Start: August 20, 2020
• Primary Completion: August 1, 2023
• Study Completion: August 1, 2023
• Last Updated: March 29, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share

Locations

SG (2)