Patient case: 52-year-old male with Colon cancer. Genetic variant: KRAS (G13D), BRAF (V600E). Other conditions: Type II Diabetes, Hypertension.

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

Summary: 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 activity of cancer cells.
  Two hundred patients diagnosed with 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 returning after treatment.

Detailed description: Artemisinins are a family of sesquiterpene trioxane anti-malarial agents derived from Sweet Wormwood (Artemisia annua L), a plant that has been used in traditional Chinese medicine for centuries. Artesunate is a derivative of artemisinin that is converted into its active metabolite dihydroartemisinin (DHA). Artesunate is a widely used antimalarial with a good safety profile and oral route of administration. Artemisinins have demonstrated broad anti-cancer effects including pro-apoptotic, anti-proliferative, anti-angiogenesis and anti-metastatic effects.
  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.
  In the NeoART trial, 200 patients with Stage II/III colorectal cancer planned for curative surgery, will be randomly allocated to receive either pre-operative oral artesunate 200mg once daily or matching placebo for two weeks prior to surgery. Patients will be followed up closely for 5 years following treatment to see if artesunate is associated with improved recurrence free survival. The safety and tolerability of neoadjuvant artesunate in colorectal cancer will also be further assessed.

Eligibility: Inclusion criteria :
  1. Aged 18 or over
  2. Histologically proven single primary site colorectal adenocarcinoma
  3. Stage II/III colorectal cancer for planned surgical resection and no clinical indication for neoadjuvant preoperative chemotherapy/ chemoradiation therapy
  4. WHO performance status 0,1 or 2
  5. Adequate full blood count: White Cell Count (WCC) >3.0 x 10 /l; Platelets >100 x 10; Haemoglobin (Hb) >8g/dL
  6. Adequate renal function: Glomerular Filtration Rate >30ml/min by Wright/Cockcroft-Gault formula
  7. Adequate hepatobiliary function: Bilirubin < 3 x Upper limit normal
  8. 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 adequate, medically approved contraceptive precautions for up to 6 weeks after the last dose of study treatment intervention.
  9. Male participants with a partner of childbearing potential must agree to use adequate, medically approved contraceptive precautions during and for 6 weeks after the last dose of the study treatment intervention
  10. Patient able and willing to provide written, informed consent for the study
  Exclusion criteria:
  1. Contraindication to use of artesunate due to hypersensitivity
  2. Pregnancy or lactation
  3. Male or female participants unwilling to use an effective method of birth control (either hormonal in the form of the contraceptive pill or barrier method of birth control accompanied by the use of a proprietary spermicidal foam/gel or film); or agreement of true abstinence (i.e. withdrawal, calendar, ovulation, symptothermal and post ovulation are not acceptable methods) from time consent is signed until 6 weeks after the last dose of study treatment intervention
  4. History of immunosuppression, hearing or balance problems
  5. Weight < 52 kg or > 110 kg
  6. Other planned intervention, apart from standard of care
  7. Any other malignant disease diagnosis within the preceding 2 years with the exception of non-melanomatous skin cancer and carcinoma in situ
  8. Lactose intolerance

Relevance to patient case: possibly relevant