title: Combining curcumin (C3-complex, Sabinsa) with standard care FOLFOX chemotherapy in patients with inoperable colorectal cancer (CUFOX): study protocol for a randomised control trial.
abstract: BACKGROUND
  The need for low toxicity adjuncts to standard care chemotherapy in inoperable colorectal cancer, with potential to improve outcomes and decrease the side-effect burden, is well recognised. Addition of the low toxicity diet-derived agent, curcumin (the active ingredient of turmeric), to standard oxaliplatin-based therapy has shown promise in numerous pre-clinical studies.
  
  
  METHODS
  This study is the first to combine daily oral curcumin with standard care FOLFOX-based (5-fluorouracil, folinic acid and oxaliplatin) chemotherapy in colorectal cancer patients with inoperable liver metastases: the CUFOX trial. CUFOX comprises a Phase 1 dose-escalation study (3 + 3 + 3 design) to determine an acceptable target dose of curcumin with which to safely proceed to a Phase IIa open-labelled randomised controlled trial. Thirty three participants with histological or cytological confirmation of inoperable colorectal cancer will then be randomised to oxaliplatin-based chemotherapy with the addition of daily oral curcumin at the target dose determined in Phase I, or to standard care oxaliplatin-based chemotherapy alone (recruiting at a ratio of 2:1).
  
  
  CONCLUSIONS
  Primary outcome measures will be the determination of a target dose which is both safe and tolerable for long-term administration to individuals in receipt of first-line oxaliplatin-based chemotherapy for inoperable colorectal cancer. Secondary outcome measures will include observation of any changes in neuropathic side-effects of chemotherapy, improvement to progression-free or overall survival and identification of putative efficacy biomarkers in plasma. The results will be disseminated via presentation at national and international conferences, via publication in appropriate peer-reviewed journals and via the Cancer Research UK/Department of Health Experimental Cancer Medicine Centre Network. This trial has full ethical and institutional approval, and commenced recruitment in February 2012.
  
  
  BACKGROUND
  ClinicalTrials.gov ( NCT01490996 , registered 7(th) December 2011), European Drug Regulating Authorities (EudraCT 2011-002289-19, registered 13(th) May 2011), UKCRN ID#10672.
authors: Department of Cancer Studies, University of Leicester, Leicester, LE2 7LX, UK. girving@doctors.org.
authors: Glen Rb
authors: GR
authors: Irving
authors: Department of Cancer Studies, University of Leicester, Leicester, LE2 7LX, UK. cooiwuji@yahoo.com.
authors: Chinenye Oo
authors: CO
authors: Iwuji
authors: Department of Cancer Studies, University of Leicester, Leicester, LE2 7LX, UK. bm11@le.ac.uk.
authors: Bruno
authors: B
authors: Morgan
authors: Department of Hepatobiliary Surgery, University Hospitals of Wales, Cardiff, CF14 4XW, UK. david.p.berry@talktalk.net.
authors: David P
authors: DP
authors: Berry
authors: Department of Cancer Studies, University of Leicester, Leicester, LE2 7LX, UK. wps1@le.ac.uk.
authors: William P
authors: WP
authors: Steward
authors: Department of Cancer Studies, University of Leicester, Leicester, LE2 7LX, UK. at107@le.ac.uk.
authors: Anne
authors: A
authors: Thomas
authors: Department of Cancer Studies, University of Leicester, Leicester, LE2 7LX, UK. kb20@le.ac.uk.
authors: Karen
authors: K
authors: Brown
authors: Department of Cancer Studies, University of Leicester, Leicester, LE2 7LX, UK. lh28@le.ac.uk.
authors: Lynne M
authors: LM
authors: Howells
mesh_terms: D000284:Administration, Oral; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D002985:Clinical Protocols; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003474:Curcumin / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004739:England; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003474:Curcumin; D002955:Leucovorin; D005472:Fluorouracil