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Artesunate 200mg oral tablets once daily for 14 days.

Matching placebo oral tablets once daily for 14 days.

Artesunate 200mg PO OD for 14 days prior to colorectal resection surgery

Artesunate 200mg

Matched placebo PO OD for 14 days prior to colorectal resection surgery

Placebo

Professor Sanjeev Krishna, FRCP, ScD, FMedSci

Dr Yolanda Augustin, MBBS, MRCP, FRCR, MSc

Nirooshun Dr Rajendran

Alison Ray

Pasha Mr Nisar

Victoria Frost

Stelios Vakis

Helen Cox

Adam Stearns

Cheryl Websdale

Jon Mr Lacy-Colson

Sally Potts

Professor Sanjeev Krishna, BMBCh, DPhil, ScD

This study evaluates the safety and effectiveness of pre-operative artesunate given orally once a day for 14 days prior to surgery in patients with Stage II/III colorectal cancer.

Artesunate is an established antimalarial drug with an excellent safety profile, is well tolerated and affordable. A number of laboratory studies and one small pilot clinical study in patients with colorectal cancer have shown that artesunate can reduce the proliferation and growth of cancer cells.

Two hundred patients diagnosed with Stage II/III operable colorectal cancer will be randomly allocated to receive oral artesunate 200mg daily or a matching placebo for 14 days prior to surgery. Patients will be followed up closely for 5 years to see if giving artesunate preoperatively reduces the risk of cancer recurring after surgery.

Artesunate is an established antimalarial drug belonging to the artemisinin class of drugs, has an excellent safety profile, is well tolerated and affordable. In last two decades, artemisinins have shown potent and broad anticancer properties in a range of cell lines and animal models, supporting the hypothesis that artemisinins have the potential to be an effective anti-cancer therapy. Multiple potential mechanisms of action include anti-proliferative effects through cell-cycle disruption, reactive oxygen species (ROS) -induced DNA damage, induction of apoptosis, anti-angiogenesis, immunomodulation and induced radiosensitivity.

Despite a multi-modality treatment approach to colorectal cancer, 5 year overall survival does not currently exceed 60%. Neoadjuvant pre-operative therapy may be more effective at eradicating micrometastases compared to adjuvant therapy delivered following the delay and immunological stress of surgery. However current neoadjuvant chemotherapy regimens are often associated with significant side effects and may result in a delay in surgery whilst patients recover. A well tolerated, affordable, novel anticancer agent that could be given to patients whilst they wait for surgery, without causing a surgical delay due to treatment related toxicity, would have a significant clinical impact on patient care.

The NeoART trial is a phase II multicentre randomised, double blind, placebo controlled trial (RCT) for patients undergoing primary surgery for Stage II/III colorectal cancers. Patients are randomised (1:1 ratio) to receive either a two week course of neoadjuvant artesunate 200mg once daily or matching placebo. Both patients and health care professionals are blinded to treatment allocation arm to minimise outcome-reporting bias. The primary endpoint of the trial is recurrence free survival two years after surgery. Secondary endpoints include 2 and 5 year overall survival, treatment related toxicity, tolerability and patient quality of life. A translational sub-study looking at predictive and prognostic biomarkers is also planned.

A Safety and Effectiveness Study of Pre-operative Artesunate in Stage II/III Colorectal Cancer

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

Using validated quality of life self-administered questionnaires

Number of patients with surgery related adverse events as assessed by CTCAE v4.0

Number of patients with Kras mutant tumours

Number of patients with Mismatch Repair (MMR) mutant tumours

Number of patients with BRAF mutant tumours

Number of patients whose tumours show PDGF upregulation/downregulation following treatment intervention

Number of patients whose tumours show PDGFR upregulation/downregulation following study intervention

Number of patients whose tumours show VEGF upregulation/downregulation following study intervention

Number of patients whose tumours show VEGFR upregulation/downregulation following study intervention

Number of patients whose tumours show an increase or reduction in proliferation markers Ki67 and CD31 following study intervention

Number of patients whose tumour samples show activation of the DDR pathway following study intervention

Number of patients who show an increase or a decrease in expression of proteins involved in the Wnt/β-catenin proliferation pathway (e.g. c-myc and cyclinD1 proteins) following study intervention

Spots Global Cancer Trial Database for antimalarial

Every month we try and update this database with for antimalarial cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.