A Safety and Effectiveness Study of Preoperative Artesunate in Stage II / III Colorectal Cancer

Randomized, double-blind, placebo-controlled phase II trial of neoadjuvant artesunate in stage II / III colorectal cancer

This study evaluates the safety and efficacy of preoperative orally administered artesunate once daily for 14 days before surgery in patients with stage II / III colorectal cancer.

Artesunate is an established antimalarial with an excellent safety profile, is well tolerated and affordable. A number of laboratory studies and a 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 operable stage II / III colorectal cancer will be assigned to receive 200 mg of oral artesunate or a corresponding placebo for 14 days prior to surgery. Patients will be followed closely for 5 years to see if artesunate preoperatively reduces the risk of cancer coming back after surgery.

Detailed description

Over the past two decades, artemisinins have shown potent and extensive anticancer properties in a range of cell lines and animal models, supporting the hypothesis that artemisinins have the potential to be an effective cancer therapy. Multiple potential mechanisms of action include anti-proliferative effects by cell cycle disruption, reactive oxygen species (ROS) -induced DNA damage, induction of apoptosis, antiangiogenesis, immunomodulation and induced radiosensitivity.

Despite a multimodal therapeutic approach to colorectal cancer, 5-year overall survival currently does not exceed 60%. Preoperative neoadjuvant therapy may be more effective in eradicating micrometastases compared to adjuvant therapy administered after the delay and immunological stress of surgery. However, current neoadjuvant chemotherapy regimens are often associated with significant side effects and may cause surgery to be delayed while patients recover. A new, well-tolerated and affordable anticancer agent that could be administered to patients while they wait for surgery, without causing surgical delay due to treatment toxicity, would have a significant clinical impact on patient care.

The NeoART trial is a multicenter, phase II, randomized, double-blind, placebo-controlled (RCT) trial for patients undergoing primary surgery for stage II / III colorectal cancers. Patients are randomized (1: 1 ratio) to receive either a two-week course of neoadjuvant artesunate 200 mg once daily or a corresponding placebo. Patients and healthcare professionals are blinded to the treatment allocation arm to minimize 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 substudy on predictive and prognostic biomarkers is also planned.

Source: https://ichgcp.net/fr/clinical-trials-registry/NCT02633098