Solid TumorPhase 1/2NCT04522284
PRECISE CURATE.AI Pilot Clinical Trial
A Phase 1/2 study testing CURATE.AI, Capecitabine and XELOX in people with Solid Tumor, run by National University Hospital, Singapore at 2 sites in Singapore.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 99 years
- Conditions the study is for
- Solid Tumor
- What is being tested?
- CURATE.AI, Capecitabine and XELOX
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesSingapore
- Study dates
- 20 Aug 2020to 1 Aug 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- General Inclusion Criteria
- 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
Who cannot join
- General Exclusion Criteria
- 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.
Show all 22Show fewer
- 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
- Specific Inclusion Criteria
- 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).
- Specific Exclusion Criteria Nil
- Specific Recruitment Criteria for Cohort 2: Ibrutinib in Waldenström macroglobulinaemia
- Specific Inclusion Criteria
- 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.
- Specific Exclusion Criteria
- 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).
- Platelet transfusion within 7 days of screening.
- Granulocyte colony stimulating factor within 7 days of screening.
Trial locations and contacts
2 sites in 1 country.
Michelle Au contact
Singapore2 sites, 2 recruiting
- Recruiting
National University Hospital
Singapore, 119074
Cheng Ean Chee, Dr
Wei Peng Yong, Dr
- Recruiting
Ng Teng Fong General Hospital
Singapore
Raghav Sundar, 67162000, raghav_sundar@nuhs.edu.sg
Hui Sin Tan, Hui_Sin_TAN@nuhs.edu.sg
About this study
Official title: Personalised, Rational, Efficacy-driven Cancer Drug Dosing Via an Artificial Intelligence SystEm - CURATE.AI (PRECISE CURATE.AI Trial)
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.
Read the detailed description
Cancer patients are given drug combinations that promote cancer cell elimination. The final drug concentration in the body must fall within a narrow range that maximises cancer elimination while minimizing toxic side effects. The complexity of this task increases significantly with the number of drugs given in combination due to increasing parameters and stochastic behaviour of a biological system. Currently, the established approach is to select maximum tolerated doses (MTD) - the highest drug doses that do not cause unacceptable side effects. Treatment efficacy does not guide dose selection. Combined with limited personalisation, this dosing strategy often results in suboptimal outcomes of the treatment.
CURATE.AI is an AI-derived, mechanism-independent, small data technology platform for personalised, dynamic dosing. CURATE.AI uses a quadratic equation to generate individualised CURATE.AI profile and dosing recommendation based on only that individual's medical data: drug doses and the corresponding response marker (e.g. blood tumour markers). Profile recalibration via CURATE.AI facilitates dynamic dosing and personalised care throughout the treatment duration, aimed at achieving the highest efficacy within pre-specified safe dose ranges.
CURATE.AI is an indication-agnostic platform that has already been applied clinically for a range of indications including in oncology. CURATE.AI can be applied to indications that demonstrate regularly measured dose-dependent relationship between the treatment dose and the treatment response (i.e. biomarker level). Currently, the gold standard of monitoring treatment response in solid tumour is via radiology (using criteria such as RECIST), which is usually done at the end of a few cycles of systemic therapy and therefore not suitable to be used as a CURATE.AI input signal for drug dose adjustment between cycles.. Additionally, haematological neoplasms often cannot be monitored with imaging. Waldenström macroglobulinaemia treatment response is assessed using an adaptation of the response criteria from the Eighth International Workshop on Waldenström macroglobulinaemia (IWWM-8) that includes blood markers. Blood-based tumour markers, e.g. carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) and immunoglobulin M (IgM) markers, are more suitable to be implemented into CURATE.AI. Apart from these traditional tumour markers, recent advances in genomic sequencing have led to the application of plasma circulating tumour DNA (ctDNA) level as a novel marker of tumour burden. In addition, the serum free light chain (sFLC) has been widely used to assess treatment response for patients with multiple myeloma and other plasma cell dyscrasias, and has shown potential as a novel marker for disease burden in Waldenström macroglobulinaemia. Therefore, serial ctDNA and sFLC measurements, may be an appropriate input for CURATE.AI.
This Pilot Clinical Trial aims to set foundation to investigate the applicability and feasibility of the CURATE.AI platform within the current clinical setting for guided dosing of various systemic therapies commonly used for solid and haematological neoplasms
Individualised CURATE.AI profiles will be generated based on each participant's response to a set of drug doses. Subsequently, the personalised CURATE.AI profile will be used to recommend the efficacy-driven dose. CURATE.AI will operate only within the safety range for each drug prespecified for each participant.
This Pilot Clinical Trial and feasibility study will inform the investigators on the logistical and practical aspects of performing a large-scale randomised study and on the suitability of CURATE.AI for guided dosing of a wider range of chemotherapy regimens. An additional objective is to explore the utility of CEA, CA19-9, Ig M, ctDNA and sFLC as tumour markers in serial measurements at weekly frequency of probing, with modulated doses. ctDNA and sFLC will be also explored as an input for CURATE.AI to generate dose recommendations, however this analysis will not be used to prospectively guide dosing.
- Conditions
- Solid Tumor
- Being tested
- CURATE.AI, Capecitabine, XELOX, XELIRI, Ibrutinib
- Keywords
- Cancer, Artificial Intelligence, CURATE.AI, XELOX, Xeliri, Xeloda, Capecitabine, Chemotherapy, Phenotypic Personalized Medicine, Ibrutinib, Waldenström macroglobulinaemia
- Medical subject headings
- Neoplasms, Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CURATE.AIDevice
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.
CapecitabineDrug
Also called XELODA
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.
XELOXDrug
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.
XELIRIDrug
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.
IbrutinibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Device: CURATE.AI; Drug: Capecitabine; Drug: XELOX; Drug: XELIRI; Drug: Ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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:
- Error/variance (biological/analytical) is sufficiently small to allow accurate predictions
- Profile can be generated sufficiently early for the participant to potentially benefit;
- Dose-dependent relationship is observed;
- Profile is actionable (i.e. fulfils the clinical investigator's pre-specified safety requirements);
- Systemic changes in the participant which require profile recalibration are rare or readily assimilated into the CURATE.AI algorithm.
Measured: Up to 12 months
Secondary outcomes (5)
Patient adherence
Percentage of participants who always adhered to the prescribed dose whenever they took their medication, as measured by the standardised pharmacovigilance protocol. Based on percentages, outcomes will be classified as Green (>90%) / Yellow (10-90%) / Red (<10%).
Measured: Up to 12 months
Timely delivery of CURATE.AI recommendations to the clinician
Percentage of CURATE.AI recommendations provided in time for the next chemotherapy cycle, across all participants and cycles. Based on percentages, outcomes will be classified as Green (100%) / Yellow (10-99%) / Red (<10%).
Measured: Up to 12 months
CURATE.AI relevance
Percentage of dosing events across all participants and cycles in which CURATE.AI recommendation is considered in the clinical decision-making process. Based on percentages, outcomes will be classified as Green (100%) / Yellow (10-99%) / Red (<10%).
Measured: Up to 12 months
Physician adherence
Percentage of CURATE.AI recommended doses that were used by the clinical investigator. Based on percentages, outcomes will be classified as Green (>70%) / Yellow (10-70%) / Red (<10%).
Measured: Up to 12 months
Clinically significant dose changes
Percentage of participants in whom the CURATE.AI-guided cumulative dose is substantially (≥10%) different from the projected standard-of-care cumulative dose. Based on percentages, outcomes will be classified as Green (>20%) / Yellow (1-20%) / Red (0%).
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2020
- Study start20 Aug 2020
- Primary completion1 Aug 2023 (estimated)
- Study completion1 Aug 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- The N.1 Institute for Health (N.1)
- Responsible party
- Sponsor
- Investigators
- Raghav Sundar, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04522284
- Sponsor's protocol ID
- 2020/00334
- Status last verified
- Mar 2023
- First submitted
- 2 Aug 2020
- Last updated
- 29 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Thummel KE, Lin YS. Sources of interindividual variability. Methods Mol Biol. 2014;1113:363-415. doi: 10.1007/978-1-62703-758-7_17.
PubMed 24523121Blasiak 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.
PubMed 31771394Rashid 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.
PubMed 30089632Ho D. Artificial intelligence in cancer therapy. Science. 2020 Feb 28;367(6481):982-983. doi: 10.1126/science.aaz3023. No abstract available.
PubMed 32108102Zarrinpar 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.
PubMed 27053773Tan 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.
PubMed 34713106
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Personalised, Rational, Efficacy-driven Cancer Drug Dosing Via an Artificial Intelligence SystEm - CURATE.AI (PRECISE CURATE.AI Trial)
- ClinicalTrials.gov ID
- NCT04522284
- Acronym / sponsor ID
- 2020/00334
- Conditions
- Solid Tumor
- Keywords
- Cancer, Artificial Intelligence, CURATE.AI, XELOX, Xeliri, Xeloda, Capecitabine, Chemotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Collaborators
- The N.1 Institute for Health (N.1)
- Study start
- 20 Aug 2020 (actual)
- Primary completion
- 1 Aug 2023 (estimated)
- Study completion
- 1 Aug 2023 (estimated)
- First posted
- 21 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Cancer patients are given drug combinations that promote cancer cell elimination. The final drug concentration in the body must fall within a narrow range that maximises cancer elimination while minimizing toxic side effects. The complexity of this task increases significantly with the number of drugs given in combination due to increasing parameters and stochastic behaviour of a biological system. Currently, the established approach is to select maximum tolerated doses (MTD) - the highest drug doses that do not cause unacceptable side effects. Treatment efficacy does not guide dose selection. Combined with limited personalisation, this dosing strategy often results in suboptimal outcomes of the treatment.
CURATE.AI is an AI-derived, mechanism-independent, small data technology platform for personalised, dynamic dosing. CURATE.AI uses a quadratic equation to generate individualised CURATE.AI profile and dosing recommendation based on only that individual's medical data: drug doses and the corresponding response marker (e.g. blood tumour markers). Profile recalibration via CURATE.AI facilitates dynamic dosing and personalised care throughout the treatment duration, aimed at achieving the highest efficacy within pre-specified safe dose ranges.
CURATE.AI is an indication-agnostic platform that has already been applied clinically for a range of indications including in oncology. CURATE.AI can be applied to indications that demonstrate regularly measured dose-dependent relationship between the treatment dose and the treatment response (i.e. biomarker level). Currently, the gold standard of monitoring treatment response in solid tumour is via radiology (using criteria such as RECIST), which is usually done at the end of a few cycles of systemic therapy and therefore not suitable to be used as a CURATE.AI input signal for drug dose adjustment between cycles.. Additionally, haematological neoplasms often cannot be monitored with imaging. Waldenström macroglobulinaemia treatment response is assessed using an adaptation of the response criteria from the Eighth International Workshop on Waldenström macroglobulinaemia (IWWM-8) that includes blood markers. Blood-based tumour markers, e.g. carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) and immunoglobulin M (IgM) markers, are more suitable to be implemented into CURATE.AI. Apart from these traditional tumour markers, recent advances in genomic sequencing have led to the application of plasma circulating tumour DNA (ctDNA) level as a novel marker of tumour burden. In addition, the serum free light chain (sFLC) has been widely used to assess treatment response for patients with multiple myeloma and other plasma cell dyscrasias, and has shown potential as a novel marker for disease burden in Waldenström macroglobulinaemia. Therefore, serial ctDNA and sFLC measurements, may be an appropriate input for CURATE.AI.
This Pilot Clinical Trial aims to set foundation to investigate the applicability and feasibility of the CURATE.AI platform within the current clinical setting for guided dosing of various systemic therapies commonly used for solid and haematological neoplasms
Individualised CURATE.AI profiles will be generated based on each participant's response to a set of drug doses. Subsequently, the personalised CURATE.AI profile will be used to recommend the efficacy-driven dose. CURATE.AI will operate only within the safety range for each drug prespecified for each participant.
This Pilot Clinical Trial and feasibility study will inform the investigators on the logistical and practical aspects of performing a large-scale randomised study and on the suitability of CURATE.AI for guided dosing of a wider range of chemotherapy regimens. An additional objective is to explore the utility of CEA, CA19-9, Ig M, ctDNA and sFLC as tumour markers in serial measurements at weekly frequency of probing, with modulated doses. ctDNA and sFLC will be also explored as an input for CURATE.AI to generate dose recommendations, however this analysis will not be used to prospectively guide dosing.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| CURATE.AI | Experimental | Device: CURATE.AI, Drug: Capecitabine, Drug: XELOX, Drug: XELIRI, Drug: Ibrutinib- 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). |
Who may qualify
- Ages
- 21 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- General Inclusion Criteria
Key exclusion criteria (22 listed)
- General Exclusion Criteria
- Specific Recruitment Criteria for Cohort 1: Capecitabine in solid tumours
- Specific Inclusion Criteria
- Metastatic solid tumours not for curative intent therapy;
- Planned for treatment with the following chemotherapy regimens: XELOX, XELIRI or single agent capecitabine.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CURATE.AIEfficacy 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. | Device | CURATE.AI |
| CapecitabineAlso: XELODATreatment 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. | Drug | CURATE.AI |
| XELOXTreatment 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. | Drug | CURATE.AI |
| XELIRITreatment 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. | Drug | CURATE.AI |
| IbrutinibTreatment 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. | Drug | CURATE.AI |
Primary outcome
Percentage of participants in whom we successfully apply CURATE.AI profile.
Time frame: Up to 12 months
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.
5 secondary outcomes
Patient adherence
Time frame: Up to 12 months
Timely delivery of CURATE.AI recommendations to the clinician
Time frame: Up to 12 months
CURATE.AI relevance
Time frame: Up to 12 months
Physician adherence
Time frame: Up to 12 months
Clinically significant dose changes
Time frame: Up to 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2023.
- Results publication: PubMed 24523121Thummel KE, Lin YS. Sources of interindividual variability. Methods Mol Biol. 2014;1113:363-415. doi: 10.1007/978-1-62703-758-7_17.
- Results publication: PubMed 31771394Blasiak 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.
- Results publication: PubMed 30089632Rashid 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.
- Results publication: PubMed 32108102Ho D. Artificial intelligence in cancer therapy. Science. 2020 Feb 28;367(6481):982-983. doi: 10.1126/science.aaz3023. No abstract available.
- Results publication: PubMed 27053773Zarrinpar 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.
- Derived from this study: PubMed 34713106Tan 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.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michelle Au contact
Raghav Sundar principal investigator
National University Hospital, Singapore
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CURATE.AI, Capecitabine and XELOX in people with Solid Tumor, run by National University Hospital, Singapore at 2 sites in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Raghav Sundar (+65 6779 5555, raghav_sundar@nuhs.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of participants in whom we successfully apply CURATE.AI profile. (time frame: Up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04522284, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2023.