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

Study Overview
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Brief Summary
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This is a Phase II randomized, double-blind, placebo-controlled trial of neoadjuvant artesunate given orally as a dose of 200 mg once a day for 14 days to patients with histologically confirmed Stage II/III colorectal cancer (CRC) awaiting surgical treatment with curative intent.

Detailed Description
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Colorectal cancer (CRC) is the third most common cancer worldwide and represents a significant health care burden with an incidence of one million new cases per year. In Vietnam, Colorectal cancer is the third most common cause of cancer deaths in men and fourth in women. Artesunate is a safe and effective antimalarial with evidence of anticancer properties across a range of cancer cell lines. Results from a pilot feasibility study in colorectal cancer patients in the UK showed that artesunate was safe and well tolerated. These findings provided the basis for a Phase II clinical trial investigating the effects of neoadjuvant artesunate on progression free survival and overall survival in Stage II/III Colorectal Cancer in Vietnamese Patients. Artesunate given orally as a dose of 200 mg once a day for 14 days to patients with histologically confirmed Stage II/III colorectal cancer (CRC) awaiting surgical treatment with curative intent.

Official Title
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Phase II Randomised, Double Blind, Placebo Controlled Trial of Neoadjuvant Artesunate in Stage II/III Colorectal Cancer in Vietnamese Patients

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: artesunate
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 or over Histologically proven single primary site colorectal adenocarcinoma 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) >8g/dL Adequate renal function : Glomerular Filtration Rate >30ml/min by Cockcroft-Gault formula Adequate hepatobiliary function : Bilirubin < 3 x Upper limit normal Female participants of child bearing potential must have a negative pregnancy test < 72 hours prior to initiating study intervention and agree to avoid pregnancy using contraceptive precautions for up to 6 weeks after the last dose of study treatment intervention Male participants with a partner of childbearing potential must agree to use 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 Exclusion Criteria: Contraindication to the use of artesunate due to hypersensitivity Pregnancy or lactation History of immunosuppression History of hearing or balance problems Weight < 42 kg or > 110 kg Other planned intervention, apart from Vietnamese 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: artesunate<br>Patients will receive 200 mg artesunate (Arinate®) per oral (PO) once daily (OD) for fourteen days prior to their planned surgery and then be followed up for 5 years following surgery. | Drug: artesunate<br>* Artesunate (Trade name : Arinate®) Artemisinins are a family of sesquiterpene trioxane anti-malarial agents derived from Sweet wormwood (Artemisia annua L) that have been used in traditional Chinese medicine for centuries to treat fevers. Artesunate, artemether and arteether are derivatives of artemisinin that are converted into their active metabolite dihydroartemisinin (DHA). Artesunate is approved for the treatment of uncomplicated and multidrug-resistant malaria and is on the WHO list of Essential Medicines (WHO., 2015).<br>* Other names: Arinate®;|
| Placebo Comparator: placebo<br>Patients will receive matching placebo tablets per oral (PO) once daily (OD) for fourteen days prior to their planned surgery and then be followed up for 5 years following surgery. | Other: placebo<br>* The matching placebo tablets contain lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, colloidal anhydrous silica and a magnesium stearate blend.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| recurrence free survival 2 years after surgery | The primary outcome measure for the comparison of the artesunate versus placebo group is recurrence free survival 2 years after surgery | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence free survival at 5 years | Recurrence free survival | 5 years | 
| Overall survival at 2 and 5 years | Overall survival | 2-5 years | 
| Colon cancer specific death at 2 and 5 years | Colon cancer specific death | 2-5 years | 
| Artesunate drug related toxicity | drug related toxicity | 5 years | 
| Pathological assessment of tumour regression (involvement of lymph nodes ; serosa ; resection margin) | Pathological assessment | 5years | 
| Surgical morbidity/mortality | Surgical morbidity/mortality | 5years | 
| Predictive value of tumour biomarkers in terms of predicting response to artesunate therapy | tumour biomarkers | 5 years |