Safety and Effectiveness Study of Pre-operative Artesunate in Stage II/ III Colorectal Cancer

NCT07095309 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: 2023-MHL-001NMRR ID-24-01879-TSI
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 6

Brief 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. 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.

Conditions

Stage II/III Colon Cancer; Bowel Cancer

Keywords

artesunate; colorectal; drug repurposing; antimalarial

Outcome Measures

Primary Outcomes (1)

• 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

  2 years following study randomisation.

Secondary Outcomes (27)

• Recurrence-Free Survival at 5 Years Post-Randomisation Assessed by Radiological and Clinical Evaluation

  5 years from study randomisation

• Overall Survival (OS) at 2 and 5 Years Post-Randomisation

  2 years and 5 years following study randomisation.

• Colon Cancer-Specific Mortality at 2 and 5 Years Post-Randomisation

  2 years and 5 years following study randomisation.

• Incidence of Artesunate-Related Toxicity Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  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

  Assessment at Day 14 following initiation of study intervention (artesunate or matching placebo).

Study Arms (2)

Artesuante

EXPERIMENTAL

Artesunate 200mg oral tablets once daily for 14 days.

Drug: Artesunate

Artesunate matching placebo

PLACEBO COMPARATOR

Matching placebo oral tablets once daily for 14 days.

Drug: Artesunate matching Placebo

Interventions

Artesunate DRUG

Artesunate 200mg PO OD for 14 days prior to colorectal resection surgery

Artesuante

Artesunate matching Placebo DRUG

Matched placebo PO OD for 14 days prior to colorectal resection surgery

Artesunate matching placebo

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Metanoic Health Ltd.: lead
• Clinical Research Malaysia: collaborator

Study Sites (6)

Hospital Sultanah Bahiyah

Alor Star, Kedah, 05460, Malaysia

Location

Hospital Kuala Lumpur

Kuala Lumpur, Kuala Lumpur, 50586, Malaysia

Location

Pusat Perubatan Universiti Malaya

Kuala Lumpur, Kuala Lumpur, 59100, Malaysia

Location

Hospital Umum Sarawak

Kuching, Sarawak, 93586, Malaysia

Location

Hospital Sungai Buloh

Sungai Buloh, Selangor, 47000, Malaysia

Location

Hospital Pulau Pinang

Pulau Pinang, 10990, Malaysia

Location

Related Publications (19)

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  PMID: 26137537 BACKGROUND

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• Krishna 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.

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• Singh 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.

  PMID: 17101767 BACKGROUND

• Steinbruck 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.

  PMID: 21156967 BACKGROUND

• Reichert 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.

  PMID: 22560712 BACKGROUND

• Nakase 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.

  PMID: 17942255 BACKGROUND

• Kim 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

• 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.

  PMID: 24316259 BACKGROUND

• Foxtrot 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.

  PMID: 23017669 BACKGROUND

• Finlay 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.

  PMID: 3416116 BACKGROUND

• Ericsson 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.

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• Efferth 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.

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• Du 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.

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• Berger TG, Dieckmann D, Efferth T, Schultz ES, Funk JO, Baur A, Schuler G. Artesunate in the treatment of metastatic uveal melanoma--first experiences. Oncol Rep. 2005 Dec;14(6):1599-603.

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• Berdelle N, Nikolova T, Quiros S, Efferth T, Kaina B. Artesunate induces oxidative DNA damage, sustained DNA double-strand breaks, and the ATM/ATR damage response in cancer cells. Mol Cancer Ther. 2011 Dec;10(12):2224-33. doi: 10.1158/1535-7163.MCT-11-0534. Epub 2011 Oct 13.

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• Beccafico S, Morozzi G, Marchetti MC, Riccardi C, Sidoni A, Donato R, Sorci G. Artesunate induces ROS- and p38 MAPK-mediated apoptosis and counteracts tumor growth in vivo in embryonal rhabdomyosarcoma cells. Carcinogenesis. 2015 Sep;36(9):1071-83. doi: 10.1093/carcin/bgv098. Epub 2015 Jul 7.

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• Anfosso L, Efferth T, Albini A, Pfeffer U. Microarray expression profiles of angiogenesis-related genes predict tumor cell response to artemisinins. Pharmacogenomics J. 2006 Jul-Aug;6(4):269-78. doi: 10.1038/sj.tpj.6500371. Epub 2006 Jan 24.

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MeSH Terms

Conditions

Intestinal Neoplasms

Interventions

Artesunate

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons

Study Officials

• Emeritus Professor Sanjeev Krishna, FRCP, ScD, FMedSci

  Centre for Affordable Diagnotics and Therapeutics

  STUDY CHAIR

• Dr Yolanda Augustin

  Centre for Affordable Diagnotics and Therapeutics

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dr Yolanda Augustin

CONTACT

+442087250446; yagustin@cadt.org.uk

Dr Nafeesa Mat Ali

CONTACT

nmatali@cadt.org.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 7, 2025
• First Posted: July 31, 2025
• Study Start: August 15, 2025
• Primary Completion (Estimated): August 30, 2032
• Study Completion (Estimated): July 31, 2033
• Last Updated: July 31, 2025

Record last verified: 2025-07

Locations

MY (6)