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

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

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.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: artesunate; Other: placebo

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.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• Vietnam
  • Hanoi, Vietnam
    • Recruiting
    • 108 Military Central Hospital
    • Contact: Le Huu Song, MD, PhD; Phone Number: +84 (0) 974845270; Email: lehuusong@108-icid.com
    • Contact: Bui Tien Sy, MD, PhD; Phone Number: +84 (0) 974552943; Email: tiensy2015@yahoo.com
    • Principal Investigator: Le Huu Song, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: artesunate; 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; 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).; Other Names: Arinate®
Placebo Comparator: placebo; 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; The matching placebo tablets contain lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, colloidal anhydrous silica and a magnesium stearate blend.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The 108 Military Central Hospital
• Collaborators: Institute of Tropical Medicine, University of Tuebingen
• Investigators: Study Director: Mai Hong Bang, MD,PhD, 108 Military Central Hospital

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2018
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: March 16, 2017
• First Submitted That Met QC Criteria: March 22, 2017
• First Posted (Actual): March 28, 2017

Study Record Updates

• Last Update Posted (Actual): January 9, 2018
• Last Update Submitted That Met QC Criteria: January 8, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Artesunate
• Other Study ID Numbers: NeoArt-V

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No