Clinical trial NCT03093129: Safety and Effectiveness Study of Pre-operative Artesunate in Stage II/III Colorectal Cancer (NeoART-V)
Official title: Phase II Randomised, Double Blind, Placebo Controlled Trial of Neoadjuvant Artesunate in Stage II/III Colorectal Cancer in Vietnamese Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Colorectal Cancer
Lead sponsor: The 108 Military Central Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Institute of Tropical Medicine, University of Tuebingen
First posted: 2017-03-28
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: recurrence free survival 2 years after surgery
timeFrame: 2 years
Secondary outcomes:
measure: Recurrence free survival at 5 years
timeFrame: 5 years
measure: Overall survival at 2 and 5 years
timeFrame: 2-5 years
measure: Colon cancer specific death at 2 and 5 years
timeFrame: 2-5 years
measure: Artesunate drug related toxicity
timeFrame: 5 years
measure: Pathological assessment of tumour regression (involvement of lymph nodes ; serosa ; resection margin)
timeFrame: 5years
measure: Surgical morbidity/mortality
timeFrame: 5years
measure: Predictive value of tumour biomarkers in terms of predicting response to artesunate therapy
timeFrame: 5 years
Other outcomes:
Locations:
city: Hanoi
country: Vietnam
facility: 108 Military Central Hospital
Study officials:
affiliation: 108 Military Central Hospital
name: Mai Hong Bang, MD,PhD
role: STUDY_DIRECTOR
References:
citation: 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.