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

Colorectal Cancer Clinical Trial

— NeoART-V  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03093129
• Other study ID #: NeoArt-V
• Status: Recruiting
• Phase: Phase 2
• First received: March 16, 2017
• Last updated: January 8, 2018
• Start date: January 8, 2018
• Est. completion date: December 2022

Study information

• Verified date: January 2018
• Source: The 108 Military Central Hospital
• Contact: Le Huu Song, MD, PhD
• Phone: +84-974845270
• Email: lehuusong[@]108-icid.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 2022
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

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:
• placebo
The matching placebo tablets contain lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, colloidal anhydrous silica and a magnesium stearate blend.

Locations

Country	Name	City	State
Vietnam	108 Military Central Hospital	Hanoi

Sponsors (2)

Lead Sponsor	Collaborator
The 108 Military Central Hospital	Institute of Tropical Medicine, University of Tuebingen

Country where clinical trial is conducted

Vietnam, 

References & Publications (1)

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. — View Citation

Outcome

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