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

Phase 2
Conditions
Colorectal Cancer
Interventions
Other: placebo
Registration Number
NCT03093129
Lead Sponsor
The 108 Military Central Hospital
Brief Summary

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

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
200
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
placeboplaceboPatients 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.
artesunateartesunatePatients 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.
Primary Outcome Measures
NameTimeMethod
recurrence free survival 2 years after surgery2 years

The primary outcome measure for the comparison of the artesunate versus placebo group is recurrence free survival 2 years after surgery

Secondary Outcome Measures
NameTimeMethod
Colon cancer specific death at 2 and 5 years2-5 years

Colon cancer specific death

Artesunate drug related toxicity5 years

drug related toxicity

Pathological assessment of tumour regression (involvement of lymph nodes ; serosa ; resection margin)5years

Pathological assessment

Overall survival at 2 and 5 years2-5 years

Overall survival

Predictive value of tumour biomarkers in terms of predicting response to artesunate therapy5 years

tumour biomarkers

Recurrence free survival at 5 years5 years

Recurrence free survival

Surgical morbidity/mortality5years

Surgical morbidity/mortality

Trial Locations

Locations (1)

108 Military Central Hospital

🇻🇳

Hanoi, Vietnam

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