Stage II/III Colon CancerPhase 2NeoART-MNCT07095309
Safety and Effectiveness Study of Pre-operative Artesunate in Stage II/ III Colorectal Cancer
A Phase 2 study testing Artesunate in people with Stage II/III Colon Cancer and Bowel Cancer, run by Metanoic Health Ltd. at 6 sites in Malaysia.
Trial summary
TThis study evaluates the safety and effectiveness of pre-operative artesunate, given orally once a day for 14 days prior to surgery, in patients with Stage II/III colorectal cancer. Artesunate is an established antimalarial drug with an excellent safety profile. It is well tolerated, affordable, and widely available. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage II/III Colon Cancer, Bowel Cancer
- What is being tested?
- Artesunate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 6 sitesMalaysia
- Study dates
- 15 Aug 2025to 31 Jul 2033
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18 or over
- Histologically proven single primary site colorectal adenocarcinoma or high grade dysplasia plus unequivocal radiological evidence of invasive cancer
- Stage II/III colorectal cancer planned for surgical resection and no clinical indication for neoadjuvant preoperative chemotherapy/chemoradiation therapy
- WHO performance status 0,1 or 2
- Adequate full blood count: White Cell Count (WCC) >3.0 x 109 /l; Platelets >100 x 109/l; Haemoglobin (Hb) >80g/L
- Adequate renal function : Glomerular Filtration Rate >30ml/min by Cockcroft-Gault formula.
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- Adequate hepatobiliary function : Total bilirubin < 3 x Upper limit norm
- Female participants of childbearing potential must have a negative pregnancy test <72 hours prior to initiating study intervention and agree to avoid pregnancy using adequate, medically approved contraceptive precautions for up to 6 weeks after the last dose of study treatment interventions.
- Male participants with a partner of childbearing potential must agree to use adequate, medically approved contraceptive precautions during and for up to 6 weeks after the last dose of the study treatment intervention.
- Patient able and willing to provide written, informed consent for the study.
Who cannot join
- Contraindication to use of artesunate due to hypersensitivity
- Pregnancy or lactation
- Male or female participants unwilling to use an effective method of birth control (either hormonal in the form of the contraceptive pill or barrier method of birth control accompanied by the use of a proprietary spermicidal foam/gel or film) ; or agreement of true abstinence from time consent is signed until 6 weeks after the last dose of study treatment intervention (i.e. withdrawal, calendar, ovulation, symptothermal and post ovulation are not acceptable methods)
- History of hearing or balance problems
- History of immunosuppression
- Patient weight < 52 kg or > 110 kg
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- Other planned intervention, apart from standard of care
- Any other malignant disease diagnosis within the preceding 2 years with the exception of non-melanomatous skin cancer and carcinoma in situ
- Lactose intolerance
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Dr Nafeesa Mat Ali contact
6 sites in 1 country
Malaysia6 sites
Hospital Sultanah Bahiyah
Alor Star, Kedah, 05460
Dr Nil Amri Mohammad Kamil, +60172152964, drneil71@hotmail.com
Wan Muhana, wanmuhana@clinicalresearch.my
Hospital Kuala Lumpur
Kuala Lumpur, Kuala Lumpur, 50586
Dr Mohana Raj, +60172152964, Mohan301979@gmail.com
Nur Aina Nabilah, aina.nabilah@clinicalresearch.my
Pusat Perubatan Universiti Malaya
Kuala Lumpur, Kuala Lumpur, 59100
Dr Ruben Xavier, +60172152964, rubengregory@ummc.edu.my
Milisha Magesvaran, milisha.koh@ummc.edu.my
Hospital Umum Sarawak
Kuching, Sarawak, 93586
Dr 'Izzati Wan Maharuddin, wanmahar.izzati@gmail.com
Syamimi, syamimi@clinicalresearch.my
Hospital Pulau Pinang
Pulau Pinang, 10990
Dr Soo Hoo Hwoei Fen, +60172152964, hwoeifen@yahoo.com
Ahmad Syarif Ibrahim, ahmad.syarif@clinicalresearch.my
Hospital Sungai Buloh
Sungai Buloh, Selangor, 47000
Dr Mohd Syafferi Masood, +60172152964, syafferi@yahoo.com
Citra Palanisamy, citra@clinicalresearch.my
About this study
Official title: Phase II Randomised, Double Blind, Placebo Controlled Trial of Neoadjuvant Artesunate in Stage II/III Colorectal Cancer
TThis study evaluates the safety and effectiveness of pre-operative artesunate, given orally once a day for 14 days prior to surgery, in patients with Stage II/III colorectal cancer.
Artesunate is an established antimalarial drug with an excellent safety profile. It is well tolerated, affordable, and widely available. Several laboratory studies and one small pilot clinical study in patients with colorectal cancer have shown that artesunate can reduce the proliferation and growth of cancer cells.
One hundred patients diagnosed with Stage II/III operable colorectal cancer will be randomly allocated to receive oral artesunate 200 mg daily or a matching placebo for 14 days prior to surgery. Patients will then be followed closely for 5 years to determine whether pre-operative artesunate reduces the risk of cancer recurrence after surgery.
Read the detailed description
Artesunate is an established antimalarial drug belonging to the artemisinin class of drugs, has an excellent safety profile, is well tolerated and affordable. In last two decades, artemisinins have shown potent and broad anticancer properties in a range of cell lines and animal models, supporting the hypothesis that artemisinins have the potential to be an effective anti-cancer therapy. Multiple potential mechanisms of action include anti-proliferative effects through cell-cycle disruption, reactive oxygen species (ROS) -induced DNA damage, induction of apoptosis, anti-angiogenesis, immunomodulation and induced radiosensitivity.
Despite a multi-modality treatment approach to colorectal cancer, 5 year overall survival does not currently exceed 60%. Neoadjuvant pre-operative therapy may be more effective at eradicating micrometastases compared to adjuvant therapy delivered following the delay and immunological stress of surgery. However current neoadjuvant chemotherapy regimens are often associated with significant side effects and may result in a delay in surgery whilst patients recover. A well tolerated, affordable, novel anticancer agent that could be given to patients whilst they wait for surgery, without causing a surgical delay due to treatment related toxicity, would have a significant clinical impact on patient care.
The NeoART trial is a phase II multicentre randomised, double blind, placebo controlled trial (RCT) for patients undergoing primary surgery for Stage II/III colorectal cancers. Patients are randomised (1:1 ratio) to receive either a two week course of neoadjuvant artesunate 200mg once daily or matching placebo. Both patients and health care professionals are blinded to treatment allocation arm to minimise outcome-reporting bias. The primary endpoint of the trial is recurrence free survival two years after surgery. Secondary endpoints include 2 and 5 year overall survival, treatment related toxicity, tolerability and patient quality of life. A translational sub-study looking at predictive and prognostic biomarkers is also planned.
- Conditions
- Stage II/III Colon Cancer, Bowel Cancer
- Being tested
- Artesunate, Artesunate matching Placebo
- Keywords
- artesunate, colorectal, drug repurposing, antimalarial
- Medical subject headings
- Intestinal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ArtesunateDrug
Artesunate 200mg PO OD for 14 days prior to colorectal resection surgery
Artesunate matching PlaceboDrug
Matched placebo PO OD for 14 days prior to colorectal resection surgery
| Study group | Role | What they receive |
|---|---|---|
| Artesuante | Experimental | Artesunate 200mg oral tablets once daily for 14 days. Receives: Drug: Artesunate |
| Artesunate matching placebo | Placebo comparator | Matching placebo oral tablets once daily for 14 days. Receives: Drug: Artesunate matching Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence-Free Survival (RFS) at 2 Years Post-Randomisation Assessed by Radiological and Clinical Evaluation
RFS is defined as the time from randomisation to the first documented recurrence of colorectal cancer (local or distant) or death from any cause, whichever occurs first. Recurrence will be assessed using standard CT scans of the chest, abdomen, and pelvis, clinical examination and measuring carcinoembryonic antigen (CEA). Confirmation of recurrence may include histological evidence where clinically indicated. Unit of Measure: Months
Measured: 2 years following study randomisation.
Secondary outcomes (27)
Recurrence-Free Survival at 5 Years Post-Randomisation Assessed by Radiological and Clinical Evaluation
RFS is defined as the time from randomisation to the first documented recurrence of colorectal cancer (local or distant) or death from any cause, whichever occurs first. Recurrence will be assessed using standard CT scans of the chest, abdomen, and pelvis, clinical examination and CEA . Histological confirmation of recurrence will be obtained where clinically indicated. Unit of Measure: Months
Measured: 5 years from study randomisation
Overall Survival (OS) at 2 and 5 Years Post-Randomisation
Survival status will be determined through clinical follow-up, hospital records, and national death registries where available. Unit of Measure: Months
Measured: 2 years and 5 years following study randomisation.
Colon Cancer-Specific Mortality at 2 and 5 Years Post-Randomisation
Measured: 2 years and 5 years following study randomisation.
Incidence of Artesunate-Related Toxicity Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
The number of participants experiencing adverse events considered related to artesunate will be recorded and graded using the CTCAE.
Unit of Measure:
Number of participants with at least one artesunate-related adverse event, by CTCAE grade.
Measured: Assessment at Day 7 following initiation of study intervention (artesunate or matching placebo).
Incidence of Artesunate-Related Toxicity Assessed by Common Terminology CTCAE v5.0
The number of participants experiencing adverse events considered related to artesunate will be recorded and graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Causality will be assessed by the site investigator and confirmed by the clinical trial safety team. Adverse events will be coded and reported by type and severity.
Measured: Assessment at Day 14 following initiation of study intervention (artesunate or matching placebo).
Incidence of Artesunate-Related Toxicity Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
The number of participants experiencing adverse events considered related to artesunate will be recorded and graded using the CTCAE. Causality will be assessed by the site investigator and confirmed by the clinical trial safety team. Adverse events will be coded and reported by type and severity.
Unit of Measure:
Number of participants with at least one artesunate-related adverse event, by CTCAE grade.
Measured: Assessment at Day 42 following initiation of study intervention (artesunate or matching placebo).
Incidence of Adverse Events Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
The number and proportion of participants experiencing any adverse events (AEs), regardless of causality, will be recorded and graded using the CTCAE.
Unit of Measure:
Number of participants with at least one adverse event, categorised by CTCAE grade.
Measured: Assessment at Day 7 following administration of study intervention (artesunate or matching placebo).
Incidence Adverse events affecting patients as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Day 14
The number and proportion of participants experiencing any adverse events (AEs), regardless of causality, will be recorded and graded using the CTCAE.
Unit of Measure:
Number of participants with at least one adverse event, categorised by CTCAE grade.
Measured: Assessment at Day 14 following study intervention
Incidence of adverse events affecting patients as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
The number and proportion of participants experiencing any adverse events (AEs), regardless of causality, will be recorded and graded using the CTCAE.
Unit of Measure:
Number of participants with at least one adverse event, categorised by CTCAE grade.
Measured: Assessment at Day 42 following study intervention
Pathological assessment of tumour regression post intervention
Tumour regression will be assessed by histopathological examination of the surgical resection specimen. The assessment will include:
- Degree of tumour regression in the primary tumour bed
- Presence of tumour involvement at the resection margins
- Evidence of tumour invasion into the serosa (pT4a) and lymph node involvement (number and proportion of positive lymph nodes).
- Histopathological evaluation
Unit of Measure:
Number and proportion of participants with positive lymph nodes, serosal involvement, and positive resection margins.
Measured: Post surgical pathology review (following Day 14 of study intervention)
Patient-Reported Quality of Life (QoL) Assessed by Validated Questionnaires at Baseline
Quality of life will be assessed using validated, self-administered questionnaires:
- EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30)
- EORTC QLQ-CR29 (Colorectal Cancer-Specific Module)
These instruments evaluate global health status/QoL, functional scales (physical, role, emotional, cognitive, social), and symptom scales. Scores for each scale range from 0 to 100. For functional and global health status scales, higher scores indicate better QoL. For symptom scales, higher scores indicate worse symptoms.
Unit of Measure:
Mean scores for each scale/domain of the EORTC QLQ-C30 and QLQ-CR29 questionnaires.
Measured: Assessment at Day 1 of study intervention (baseline assessment)
Patient-Reported Quality of Life (QoL) Assessed by Validated Questionnaires
Quality of life will be assessed using validated, self-administered questionnaires:
- EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30)
- EORTC QLQ-CR29 (Colorectal Cancer-Specific Module)
These instruments evaluate global health status/QoL, functional scales (physical, role, emotional, cognitive, social), and symptom scales. Scores for each scale range from 0 to 100. For functional and global health status scales, higher scores indicate better QoL. For symptom scales, higher scores indicate worse symptoms.
Unit of Measure:
Mean scores for each scale/domain of the EORTC QLQ-C30 and QLQ-CR29 questionnaires.
Measured: Assessment at Day 7 of study intervention
Patient-Reported Quality of Life (QoL) Assessed by Validated Questionnaires post intervention
Quality of life will be assessed using validated, self-administered questionnaires: 1. EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30) 2. EORTC QLQ-CR29 (Colorectal Cancer-Specific Module) These instruments evaluate global health status/QoL, functional scales (physical, role, emotional, cognitive, social), and symptom scales. Scores for each scale range from 0 to 100. For functional and global health status scales, higher scores indicate better QoL. For symptom scales, higher scores indicate worse symptoms. Unit of Measure: Mean scores for each scale/domain of the EORTC QLQ-C30 and QLQ-CR29 questionnaires.
Measured: Assessment at Day 14 of study intervention
Incidence of Surgery-Related Adverse Events Assessed by CTCAE v5.0
The number and proportion of participants experiencing surgery-related adverse events (AEs) will be recorded. Events will be graded using the CTCAE version 5.0, with severity classified from Grade 1 (mild) to Grade 5 (death related to AE). Events of interest include, but are not limited to, surgical site infection, anastomotic leak, wound dehiscence, postoperative bleeding, and thromboembolic events.
Unit of Measure:
Number of participants with at least one surgery-related AE, categorised by CTCAE grade.
Measured: From time of surgery up to 3 months post surgery
Predictive value of tumour marker Carcinoma Embryonic Antigen (CEA) kinetics in terms of predicting response to artesunate therapy
Carcinoembryonic Antigen (CEA) levels will be measured in blood samples and their predictive value for response to artesunate therapy. he predictive value will be evaluated by correlating CEA with pathological tumour regression grade and recurrence-free survival.
Unit of Measure:
Change in serum CEA levels (ng/mL)
Measured: Day 1 of study intervention (baseline assessment).
Predictive value of tumour marker Carcinoma Embryonic Antigen (CEA) kinetics in terms of predicting response to artesunate therapy
Carcinoembryonic Antigen (CEA) levels will be measured in blood samples and their predictive value for response to artesunate therapy. he predictive value will be evaluated by correlating CEA with pathological tumour regression grade and recurrence-free survival.
Unit of Measure:
Change in serum CEA levels (ng/mL)
Measured: Assessment at Day 7 of study intervention
Predictive value of tumour marker Carcinoma Embryonic Antigen (CEA) kinetics in terms of predicting response to artesunate therapy
Carcinoembryonic Antigen (CEA) levels will be measured in blood samples and their predictive value for response to artesunate therapy. he predictive value will be evaluated by correlating CEA with pathological tumour regression grade and recurrence-free survival.
Unit of Measure:
Change in serum CEA levels (ng/mL)
Measured: Assessment at Day 14 of study intervention
Predictive value of tumour marker Carcinoma Embryonic Antigen (CEA) kinetics in terms of predicting response to artesunate therapy
Carcinoembryonic Antigen (CEA) levels will be measured in blood samples and their predictive value for response to artesunate therapy. he predictive value will be evaluated by correlating CEA with pathological tumour regression grade and recurrence-free survival.
Unit of Measure:
Change in serum CEA levels (ng/mL)
Measured: Assessment at Day 42 of study intervention
Immunohistochemical analyses of paraffin-embedded tumour sections to assess Kirsten rat sarcoma viral oncogene homolog (Kras) mutation status
KRAS mutation status will be assessed in tumour tissue sections obtained from pre-intervention (diagnostic biopsy, Day 0) and post-intervention (surgical resection, Day 15) samples. Immunohistochemistry (IHC) will be performed. Comparisons will be made to evaluate changes in mutation status and association with response to artesunate therapy.
Unit of Measure:
Number and proportion (%) of participants with KRAS mutant tumours at each time point.
Measured: Pre and post intervention tumour samples from patients (Day 0 and Day 15)
Immunohistochemical analyses of paraffin-embedded tumour sections to assess Mismatch Repair (MMR) status
Mismatch Repair (MMR) status will be assessed in tumour tissue sections obtained from pre-intervention (diagnostic biopsy, Day 0) and post-intervention (surgical resection, Day 15) samples. Immunohistochemistry (IHC) will be performed.
Unit of Measure:
Number and proportion (%) of participants with MMR-deficient tumours at each time p
Measured: Pre and post intervention tumour samples from patients (Day 0 and Day 15)
Immunohistochemical analyses of paraffin-embedded tumour for v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation status
Number of patients with BRAF mutant tumours
Measured: Pre and post intervention tumour samples from patients (Day 0 and Day 15)
Immunohistochemical analyses of paraffin-embedded tumour for Platelet derived growth factor (PDGF) expression
Number of patients whose tumours show PDGF upregulation/downregulation following treatment intervention
Measured: Pre and post intervention tumour samples from patients (Day 0 and Day 15)
Immunohistochemical analyses of paraffin-embedded tumour for Vascular endothelial Growth Factor (VEGF) expression
Number of patients whose tumours show VEGF upregulation/downregulation following study intervention
Measured: Pre and post intervention tumour samples from patients (Day 0 and Day 15)
Immunohistochemical analyses of paraffin-embedded tumour on Vascular endothelial Growth Factor Receptor (VEGFR) expression
Number of patients whose tumours show VEGFR upregulation/downregulation following study intervention
Measured: Pre and post intervention tumour samples from patients (Day 0 and Day 15)
Determination of proliferative activity (Ki-67 staining, Cluster of Differentiation 31 protein (CD31) staining)
Number of patients whose tumours show an increase or reduction in proliferation markers Ki67 and CD31 following study intervention
Measured: Pre and post intervention tumour samples from patients (Day 0 and Day 15)
Determination of activation of the Deoxyribonucleic acid damage response (DDR) pathway
Number of patients whose tumour samples show activation of the DDR pathway following study intervention
Measured: Pre and post intervention tumour samples from patients (Day 0 and Day 15)
Wnt/β-catenin proliferation pathway protein expression (e.g. c-myc and cyclinD1 proteins)
Number of patients who show an increase or a decrease in expression of proteins involved in the Wnt/β-catenin proliferation pathway (e.g. c-myc and cyclinD1 proteins) following study intervention
Measured: Pre and post intervention tumour samples from patients (Day 0 and Day 15)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2025
- Study start15 Aug 2025 (estimated)
- Primary completion30 Aug 2032 (estimated)
- Study completion31 Jul 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Stage II/III Colon CancerStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a Phase II randomised, placebo-controlled, double-blind trial of neoadjuvant oral artesunate 200 mg once daily for 14 days in patients with histologically confirmed colorectal cancer (CRC) Stage II/III awaiting surgical treatment with curative intent. The study null hypothesis is that there is no difference in survival outcomes between patients with Stage II/III colorectal cancer who receive neoadjuvant artesunate 200 mg once daily for 14 days prior to surgery and those receiving a matching placebo tablet. A randomised, placebo-controlled, double-blind design has been chosen to minimise potential researcher bias. A placebo arm is included as there is currently no standard neoadjuvant treatment in Stage II/III colon cancer.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Metanoic Health Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Clinical Research Malaysia
- Responsible party
- Sponsor
- Investigators
- Emeritus Professor Sanjeev Krishna, FRCP, ScD, FMedSci, Study chair, Centre for Affordable Diagnotics and TherapeuticsDr Yolanda Augustin, Principal investigator, Centre for Affordable Diagnotics and Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07095309
- Sponsor's protocol ID
- 2023-MHL-001
- Other IDs
- NMRR ID-24-01879-TSI
- Acronym
- NeoART-M
- Status last verified
- Jul 2025
- First submitted
- 7 Jul 2025
- Last updated
- 31 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Krishna S, Ganapathi S, Ster IC, Saeed ME, Cowan M, Finlayson C, Kovacsevics H, Jansen H, Kremsner PG, Efferth T, Kumar D. A Randomised, Double Blind, Placebo-Controlled Pilot Study of Oral Artesunate Therapy for Colorectal Cancer. EBioMedicine. 2014 Nov 15;2(1):82-90. doi: 10.1016/j.ebiom.2014.11.010. eCollection 2015 Jan.
PubMed 26137537Kremsner PG, Krishna S. Antimalarial combinations. Lancet. 2004 Jul 17-23;364(9430):285-94. doi: 10.1016/S0140-6736(04)16680-4.
PubMed 15262108Krishna S, Bustamante L, Haynes RK, Staines HM. Artemisinins: their growing importance in medicine. Trends Pharmacol Sci. 2008 Oct;29(10):520-7. doi: 10.1016/j.tips.2008.07.004. Epub 2008 Aug 25.
PubMed 18752857Schoenfeld DA. Sample-size formula for the proportional-hazards regression model. Biometrics. 1983 Jun;39(2):499-503.
PubMed 6354290Singh NP, Panwar VK. Case report of a pituitary macroadenoma treated with artemether. Integr Cancer Ther. 2006 Dec;5(4):391-4. doi: 10.1177/1534735406295311.
PubMed 17101767Steinbruck L, Pereira G, Efferth T. Effects of artesunate on cytokinesis and G(2)/M cell cycle progression of tumour cells and budding yeast. Cancer Genomics Proteomics. 2010 Nov-Dec;7(6):337-46.
PubMed 21156967Reichert S, Reinboldt V, Hehlgans S, Efferth T, Rodel C, Rodel F. A radiosensitizing effect of artesunate in glioblastoma cells is associated with a diminished expression of the inhibitor of apoptosis protein survivin. Radiother Oncol. 2012 Jun;103(3):394-401. doi: 10.1016/j.radonc.2012.03.018. Epub 2012 May 3.
PubMed 22560712Nakase I, Lai H, Singh NP, Sasaki T. Anticancer properties of artemisinin derivatives and their targeted delivery by transferrin conjugation. Int J Pharm. 2008 Apr 16;354(1-2):28-33. doi: 10.1016/j.ijpharm.2007.09.003. Epub 2007 Sep 6.
PubMed 17942255Kim SJ., Kim MS., Lee JW., Lee CH., Yoo, H., Shin, SH., et al. Dihydroartemisinin enhances radiosensitivity of human glioma cells in vitro. J Cancer Res Clin Oncol. 2006;132 :129-135. Krishna K., Ganapathi S., Ster IS., Saeed MEM., Cowan M., Finlayson C., Kovacsevics H., Jansen H., Kremsner PG., Efferth T., Kumar D. A Randomised, Double Blind,Placebo Controlled Pilot Study of Oral Artesunate Therapy for Colorectal Cancer. EBioMedicine 2015;2(1) :82-90 Kreeftmeijer-Vegter, A. R., P. J. van Genderen., Visser LG., Bierman WF., Clerinx J., van Veldhuizen CK., de Vries PJ. "Treatment outcome of intravenous artesunate in patients with severe malaria in the Netherlands and Belgium." Malar J.2012;11:102. Lai H., Nakase I., Lacoste E., Singh NP., Sasaki. Artemisinin-transferrin conjugate retards growth of breast tumors in the rat. Anticancer Res 2009;29 :3807-3810.
Ho WE, Peh HY, Chan TK, Wong WS. Artemisinins: pharmacological actions beyond anti-malarial. Pharmacol Ther. 2014 Apr;142(1):126-39. doi: 10.1016/j.pharmthera.2013.12.001. Epub 2013 Dec 6.
PubMed 24316259Foxtrot Collaborative Group. Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial. Lancet Oncol. 2012 Nov;13(11):1152-60. doi: 10.1016/S1470-2045(12)70348-0. Epub 2012 Sep 25.
PubMed 23017669Finlay IG, Meek D, Brunton F, McArdle CS. Growth rate of hepatic metastases in colorectal carcinoma. Br J Surg. 1988 Jul;75(7):641-4. doi: 10.1002/bjs.1800750707.
PubMed 3416116Ericsson T, Blank A, von Hagens C, Ashton M, Abelo A. Population pharmacokinetics of artesunate and dihydroartemisinin during long-term oral administration of artesunate to patients with metastatic breast cancer. Eur J Clin Pharmacol. 2014 Dec;70(12):1453-63. doi: 10.1007/s00228-014-1754-2. Epub 2014 Sep 25.
PubMed 25248945Efferth T, Dunstan H, Sauerbrey A, Miyachi H, Chitambar CR. The anti-malarial artesunate is also active against cancer. Int J Oncol. 2001 Apr;18(4):767-73. doi: 10.3892/ijo.18.4.767.
PubMed 11251172Du JH, Zhang HD, Ma ZJ, Ji KM. Artesunate induces oncosis-like cell death in vitro and has antitumor activity against pancreatic cancer xenografts in vivo. Cancer Chemother Pharmacol. 2010 Apr;65(5):895-902. doi: 10.1007/s00280-009-1095-5. Epub 2009 Aug 19.
PubMed 19690861
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Randomised, Double Blind, Placebo Controlled Trial of Neoadjuvant Artesunate in Stage II/III Colorectal Cancer
- ClinicalTrials.gov ID
- NCT07095309
- Acronym / sponsor ID
- NeoART-M / 2023-MHL-001
- Conditions
- Stage II/III Colon Cancer, Bowel Cancer
- Keywords
- artesunate, colorectal, drug repurposing, antimalarial
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Metanoic Health Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Clinical Research Malaysia
- Study start
- 15 Aug 2025 (estimated)
- Primary completion
- 30 Aug 2032 (estimated)
- Study completion
- 31 Jul 2033 (estimated)
- First posted
- 31 Jul 2025 (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.
TThis study evaluates the safety and effectiveness of pre-operative artesunate, given orally once a day for 14 days prior to surgery, in patients with Stage II/III colorectal cancer.
Artesunate is an established antimalarial drug with an excellent safety profile. It is well tolerated, affordable, and widely available. Several laboratory studies and one small pilot clinical study in patients with colorectal cancer have shown that artesunate can reduce the proliferation and growth of cancer cells.
One hundred patients diagnosed with Stage II/III operable colorectal cancer will be randomly allocated to receive oral artesunate 200 mg daily or a matching placebo for 14 days prior to surgery. Patients will then be followed closely for 5 years to determine whether pre-operative artesunate reduces the risk of cancer recurrence after surgery.
Detailed description
Artesunate is an established antimalarial drug belonging to the artemisinin class of drugs, has an excellent safety profile, is well tolerated and affordable. In last two decades, artemisinins have shown potent and broad anticancer properties in a range of cell lines and animal models, supporting the hypothesis that artemisinins have the potential to be an effective anti-cancer therapy. Multiple potential mechanisms of action include anti-proliferative effects through cell-cycle disruption, reactive oxygen species (ROS) -induced DNA damage, induction of apoptosis, anti-angiogenesis, immunomodulation and induced radiosensitivity.
Despite a multi-modality treatment approach to colorectal cancer, 5 year overall survival does not currently exceed 60%. Neoadjuvant pre-operative therapy may be more effective at eradicating micrometastases compared to adjuvant therapy delivered following the delay and immunological stress of surgery. However current neoadjuvant chemotherapy regimens are often associated with significant side effects and may result in a delay in surgery whilst patients recover. A well tolerated, affordable, novel anticancer agent that could be given to patients whilst they wait for surgery, without causing a surgical delay due to treatment related toxicity, would have a significant clinical impact on patient care.
The NeoART trial is a phase II multicentre randomised, double blind, placebo controlled trial (RCT) for patients undergoing primary surgery for Stage II/III colorectal cancers. Patients are randomised (1:1 ratio) to receive either a two week course of neoadjuvant artesunate 200mg once daily or matching placebo. Both patients and health care professionals are blinded to treatment allocation arm to minimise outcome-reporting bias. The primary endpoint of the trial is recurrence free survival two years after surgery. Secondary endpoints include 2 and 5 year overall survival, treatment related toxicity, tolerability and patient quality of life. A translational sub-study looking at predictive and prognostic biomarkers is also planned.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a Phase II randomised, placebo-controlled, double-blind trial of neoadjuvant oral artesunate 200 mg once daily for 14 days in patients with histologically confirmed colorectal cancer (CRC) Stage II/III awaiting surgical treatment with curative intent. The study null hypothesis is that there is no difference in survival outcomes between patients with Stage II/III colorectal cancer who receive neoadjuvant artesunate 200 mg once daily for 14 days prior to surgery and those receiving a matching placebo tablet. A randomised, placebo-controlled, double-blind design has been chosen to minimise potential researcher bias. A placebo arm is included as there is currently no standard neoadjuvant treatment in Stage II/III colon cancer.
| Arm | Type | Receives |
|---|---|---|
| Artesuante | Experimental | Drug: ArtesunateArtesunate 200mg oral tablets once daily for 14 days. |
| Artesunate matching placebo | Placebo comparator | Drug: Artesunate matching PlaceboMatching placebo oral tablets once daily for 14 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Aged 18 or over
- Histologically proven single primary site colorectal adenocarcinoma or high grade dysplasia plus unequivocal radiological evidence of invasive cancer
- Stage II/III colorectal cancer planned for surgical resection and no clinical indication for neoadjuvant preoperative chemotherapy/chemoradiation therapy
- WHO performance status 0,1 or 2
- Adequate full blood count: White Cell Count (WCC) >3.0 x 109 /l; Platelets >100 x 109/l; Haemoglobin (Hb) >80g/L
Key exclusion criteria (9 listed)
- Contraindication to use of artesunate due to hypersensitivity
- Pregnancy or lactation
- Male or female participants unwilling to use an effective method of birth control (either hormonal in the form of the contraceptive pill or barrier method of birth control accompanied by the use of a proprietary spermicidal foam/gel or film) ; or agreement of true abstinence from time consent is signed until 6 weeks after the last dose of study treatment intervention (i.e. withdrawal, calendar, ovulation, symptothermal and post ovulation are not acceptable methods)
- History of hearing or balance problems
- History of immunosuppression
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 |
|---|---|---|
| ArtesunateArtesunate 200mg PO OD for 14 days prior to colorectal resection surgery | Drug | Artesuante |
| Artesunate matching PlaceboMatched placebo PO OD for 14 days prior to colorectal resection surgery | Drug | Artesunate matching placebo |
Primary outcome
Recurrence-Free Survival (RFS) at 2 Years Post-Randomisation Assessed by Radiological and Clinical Evaluation
Time frame: 2 years following study randomisation.
RFS is defined as the time from randomisation to the first documented recurrence of colorectal cancer (local or distant) or death from any cause, whichever occurs first. Recurrence will be assessed using standard CT scans of the chest, abdomen, and pelvis, clinical examination and measuring carcinoembryonic antigen (CEA). Confirmation of recurrence may include histological evidence where clinically indicated. Unit of Measure: Months
27 secondary outcomes
Recurrence-Free Survival at 5 Years Post-Randomisation Assessed by Radiological and Clinical Evaluation
Time frame: 5 years from study randomisation
Overall Survival (OS) at 2 and 5 Years Post-Randomisation
Time frame: 2 years and 5 years following study randomisation.
Colon Cancer-Specific Mortality at 2 and 5 Years Post-Randomisation
Time frame: 2 years and 5 years following study randomisation.
Incidence of Artesunate-Related Toxicity Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Time frame: Assessment at Day 7 following initiation of study intervention (artesunate or matching placebo).
Incidence of Artesunate-Related Toxicity Assessed by Common Terminology CTCAE v5.0
Time frame: Assessment at Day 14 following initiation of study intervention (artesunate or matching placebo).
Incidence of Artesunate-Related Toxicity Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Time frame: Assessment at Day 42 following initiation of study intervention (artesunate or matching placebo).
Incidence of Adverse Events Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Time frame: Assessment at Day 7 following administration of study intervention (artesunate or matching placebo).
Incidence Adverse events affecting patients as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Day 14
Time frame: Assessment at Day 14 following study intervention
Incidence of adverse events affecting patients as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Time frame: Assessment at Day 42 following study intervention
Pathological assessment of tumour regression post intervention
Time frame: Post surgical pathology review (following Day 14 of study intervention)
Patient-Reported Quality of Life (QoL) Assessed by Validated Questionnaires at Baseline
Time frame: Assessment at Day 1 of study intervention (baseline assessment)
Patient-Reported Quality of Life (QoL) Assessed by Validated Questionnaires
Time frame: Assessment at Day 7 of study intervention
Patient-Reported Quality of Life (QoL) Assessed by Validated Questionnaires post intervention
Time frame: Assessment at Day 14 of study intervention
Incidence of Surgery-Related Adverse Events Assessed by CTCAE v5.0
Time frame: From time of surgery up to 3 months post surgery
Predictive value of tumour marker Carcinoma Embryonic Antigen (CEA) kinetics in terms of predicting response to artesunate therapy
Time frame: Day 1 of study intervention (baseline assessment).
Predictive value of tumour marker Carcinoma Embryonic Antigen (CEA) kinetics in terms of predicting response to artesunate therapy
Time frame: Assessment at Day 7 of study intervention
Predictive value of tumour marker Carcinoma Embryonic Antigen (CEA) kinetics in terms of predicting response to artesunate therapy
Time frame: Assessment at Day 14 of study intervention
Predictive value of tumour marker Carcinoma Embryonic Antigen (CEA) kinetics in terms of predicting response to artesunate therapy
Time frame: Assessment at Day 42 of study intervention
Immunohistochemical analyses of paraffin-embedded tumour sections to assess Kirsten rat sarcoma viral oncogene homolog (Kras) mutation status
Time frame: Pre and post intervention tumour samples from patients (Day 0 and Day 15)
Immunohistochemical analyses of paraffin-embedded tumour sections to assess Mismatch Repair (MMR) status
Time frame: Pre and post intervention tumour samples from patients (Day 0 and Day 15)
Immunohistochemical analyses of paraffin-embedded tumour for v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation status
Time frame: Pre and post intervention tumour samples from patients (Day 0 and Day 15)
Immunohistochemical analyses of paraffin-embedded tumour for Platelet derived growth factor (PDGF) expression
Time frame: Pre and post intervention tumour samples from patients (Day 0 and Day 15)
Immunohistochemical analyses of paraffin-embedded tumour for Vascular endothelial Growth Factor (VEGF) expression
Time frame: Pre and post intervention tumour samples from patients (Day 0 and Day 15)
Immunohistochemical analyses of paraffin-embedded tumour on Vascular endothelial Growth Factor Receptor (VEGFR) expression
Time frame: Pre and post intervention tumour samples from patients (Day 0 and Day 15)
Determination of proliferative activity (Ki-67 staining, Cluster of Differentiation 31 protein (CD31) staining)
Time frame: Pre and post intervention tumour samples from patients (Day 0 and Day 15)
Determination of activation of the Deoxyribonucleic acid damage response (DDR) pathway
Time frame: Pre and post intervention tumour samples from patients (Day 0 and Day 15)
Wnt/β-catenin proliferation pathway protein expression (e.g. c-myc and cyclinD1 proteins)
Time frame: Pre and post intervention tumour samples from patients (Day 0 and Day 15)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2025.
- Background: PubMed 26137537Krishna S, Ganapathi S, Ster IC, Saeed ME, Cowan M, Finlayson C, Kovacsevics H, Jansen H, Kremsner PG, Efferth T, Kumar D. A Randomised, Double Blind, Placebo-Controlled Pilot Study of Oral Artesunate Therapy for Colorectal Cancer. EBioMedicine. 2014 Nov 15;2(1):82-90. doi: 10.1016/j.ebiom.2014.11.010. eCollection 2015 Jan.
- Background: PubMed 15262108Kremsner PG, Krishna S. Antimalarial combinations. Lancet. 2004 Jul 17-23;364(9430):285-94. doi: 10.1016/S0140-6736(04)16680-4.
- Background: PubMed 18752857Krishna S, Bustamante L, Haynes RK, Staines HM. Artemisinins: their growing importance in medicine. Trends Pharmacol Sci. 2008 Oct;29(10):520-7. doi: 10.1016/j.tips.2008.07.004. Epub 2008 Aug 25.
- Background: PubMed 6354290Schoenfeld DA. Sample-size formula for the proportional-hazards regression model. Biometrics. 1983 Jun;39(2):499-503.
- Background: PubMed 17101767Singh NP, Panwar VK. Case report of a pituitary macroadenoma treated with artemether. Integr Cancer Ther. 2006 Dec;5(4):391-4. doi: 10.1177/1534735406295311.
- Background: PubMed 21156967Steinbruck L, Pereira G, Efferth T. Effects of artesunate on cytokinesis and G(2)/M cell cycle progression of tumour cells and budding yeast. Cancer Genomics Proteomics. 2010 Nov-Dec;7(6):337-46.
- Background: PubMed 22560712Reichert S, Reinboldt V, Hehlgans S, Efferth T, Rodel C, Rodel F. A radiosensitizing effect of artesunate in glioblastoma cells is associated with a diminished expression of the inhibitor of apoptosis protein survivin. Radiother Oncol. 2012 Jun;103(3):394-401. doi: 10.1016/j.radonc.2012.03.018. Epub 2012 May 3.
- Background: PubMed 17942255Nakase I, Lai H, Singh NP, Sasaki T. Anticancer properties of artemisinin derivatives and their targeted delivery by transferrin conjugation. Int J Pharm. 2008 Apr 16;354(1-2):28-33. doi: 10.1016/j.ijpharm.2007.09.003. Epub 2007 Sep 6.
- BackgroundKim SJ., Kim MS., Lee JW., Lee CH., Yoo, H., Shin, SH., et al. Dihydroartemisinin enhances radiosensitivity of human glioma cells in vitro. J Cancer Res Clin Oncol. 2006;132 :129-135. Krishna K., Ganapathi S., Ster IS., Saeed MEM., Cowan M., Finlayson C., Kovacsevics H., Jansen H., Kremsner PG., Efferth T., Kumar D. A Randomised, Double Blind,Placebo Controlled Pilot Study of Oral Artesunate Therapy for Colorectal Cancer. EBioMedicine 2015;2(1) :82-90 Kreeftmeijer-Vegter, A. R., P. J. van Genderen., Visser LG., Bierman WF., Clerinx J., van Veldhuizen CK., de Vries PJ. "Treatment outcome of intravenous artesunate in patients with severe malaria in the Netherlands and Belgium." Malar J.2012;11:102. Lai H., Nakase I., Lacoste E., Singh NP., Sasaki. Artemisinin-transferrin conjugate retards growth of breast tumors in the rat. Anticancer Res 2009;29 :3807-3810.
- Background: PubMed 24316259Ho WE, Peh HY, Chan TK, Wong WS. Artemisinins: pharmacological actions beyond anti-malarial. Pharmacol Ther. 2014 Apr;142(1):126-39. doi: 10.1016/j.pharmthera.2013.12.001. Epub 2013 Dec 6.
- Background: PubMed 23017669Foxtrot Collaborative Group. Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial. Lancet Oncol. 2012 Nov;13(11):1152-60. doi: 10.1016/S1470-2045(12)70348-0. Epub 2012 Sep 25.
- Background: PubMed 3416116Finlay IG, Meek D, Brunton F, McArdle CS. Growth rate of hepatic metastases in colorectal carcinoma. Br J Surg. 1988 Jul;75(7):641-4. doi: 10.1002/bjs.1800750707.
- Individual participant dataSharing planned: Undecided
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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.
Dr Nafeesa Mat Ali contact
Emeritus Professor Sanjeev Krishna, FRCP, ScD, FMedSci study chair
Centre for Affordable Diagnotics and Therapeutics
Dr Yolanda Augustin principal investigator
Centre for Affordable Diagnotics and Therapeutics
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Artesunate in people with Stage II/III Colon Cancer and Bowel Cancer, run by Metanoic Health Ltd. at 6 sites in Malaysia.
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 10 inclusion and 9 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: opening soon, as of the sponsor's last update on 31 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Malaysia. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dr Yolanda Augustin (+442087250446, yagustin@cadt.org.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrence-Free Survival (RFS) at 2 Years Post-Randomisation Assessed by Radiological and Clinical Evaluation (time frame: 2 years following study randomisation.). 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 NCT07095309, which also lists 19 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 31 Jul 2025.