Combining Curcumin With FOLFOX Chemotherapy in Patients With Inoperable Colorectal Cancer (CUFOX)
Oral curcumin (complex C3, Sabinsa Corp, Utah) will be given to patients with inoperable colorectal metastases who will be commencing standard care oxaliplatin-based (FOLFOX) chemotherapy for up to 12 cycles(approximately 6 months) of treatment.
Primary measurements focus on safety and tolerability. These will be recorded in real-time and report the number and severity of adverse events.
Secondary measurements will include efficacy, (measured by response rate with RECIST and overall survival in months) supported by biomarker analysis.
|Colonic Cancer Metastasis||Drug: Oral complex C3 curcumin + chemotherapy Drug: Chemotherapy only||Phase 1 Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase I/IIa Study Combining Curcumin (Curcumin C3-Complex, Sabinsa) With Standard Care FOLFOX Chemotherapy in Patients With Inoperable Colorectal Cancer.|
- Completion of dose escalation over 2 cycles of therapy [ Time Frame: 1 year ]Patients will start curcumin a week prior to chemotherapy. Upon completion of two cycles of therapy without dose-limiting toxicity in 3 consecutive patients, the dose will be escalated for the next 3 patients. Real-time adverse event reporting will be undertaken to record number and severity of events.
- Completion of (or withdrawal from) chemotherapy [ Time Frame: Up to 6 months ]Compliance in the study will be measured in months/cycles of therapy tolerated. Reasons for withdrawal or cessation will be documented which will include mortality, adverse events and patient reported outcomes of tolerance to the protocol regimen.
- Efficacy [ Time Frame: Up to 7 years ]Response rate will be measured using RECIST. Overall survival will be measured in months.
|Study Start Date:||February 2012|
|Estimated Study Completion Date:||February 2019|
|Estimated Primary Completion Date:||February 2019 (Final data collection date for primary outcome measure)|
Active Comparator: Chemotherapy only
Patients receiving up to 12 cycles of therapy. Standard care pathway management.
Drug: Chemotherapy only
Standard care chemotherapy
Other Name: FOLFOX (protocol includes changes to XELOX - capecitabine)
Experimental: Chemotherapy plus curcumin
Patients taking daily oral curcumin for up to 12 cycles of therapy. Standard care pathway management.
Drug: Oral complex C3 curcumin + chemotherapy
Daily oral capsule(s)
Other Name: C3-complex curcumin (diferuloylmethane)
Hypothesis Combination of oral curcumin with FOLFOX-based chemotherapy will be a safe and tolerated regimen for long-term administration to patients with colorectal metastases.
To establish a tolerated dose of daily oral curcumin to be taken long-term with FOLFOX-based chemotherapy in patients with metastatic colorectal cancer will be conducted to assess:
1. Safety, tolerability and feasibility of administering oral curcumin at increasing doses escalating to 4 capsules (≈2 g C3-complex) during FOLFOX-based chemotherapy and continued for the duration of the chemotherapy course.
- To observe any changes to the neuropathic side-effects of chemotherapy.
- To observe potential for efficacy in terms of disease response and survival.
- To identify putative biomarkers in plasma.
This is a phase I/IIa study:
Phase I will be a traditional escalation response design study (or 3+3+3) to firstly assess the safety of this combination and identify a maximum tolerated dose up to 4 g per day.
Phase IIa will be a randomised control study comparing curcumin and FOLFOX with FOLFOX alone, recruited at a 2:1 ratio respectively.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01490996
|Dept Oncology, Leicester Royal Infirmary|
|Leicester, United Kingdom, LE1 2WW|
|Principal Investigator:||Anne L Thomas, PhD FRCS||University of Leicester/University Hospitals Leicester|