Combining Curcumin With FOLFOX Chemotherapy in Patients With Inoperable Colorectal Cancer

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.

Primary objectives

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:

• 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.

Secondary objectives

• 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.

Inclusion criteria

• Histological or cytological diagnosis of metastatic colorectal cancer
• Measurable disease by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) (Appendix 1)
• Adequate haematological, hepatic and renal function
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1
• Patients must have recovered from effects of any recent major surgery
• Willing to use contraception if applicable
• Informed consent
• Life expectancy estimated to be more than 12 weeks

Exclusion criteria

• Main exclusion criteria
• Contraindications to FOLFOX chemotherapy: Peripheral neuropathy NCI CTC >1, Liver failure, uncontrolled coronary heart disease, myocardial infarction within the previous 6 months.
• Unwilling or unable to comply with the study protocol.
• Patients who are pregnant or lactating or contemplating pregnancy. Patients or their partners who become pregnant during the study will be referred to the appropriate experts.
• Undergone chemotherapy (other than adjuvant for CRC) or participating in another drug study.
• Previous cancer <5 years (other than colorectal, basal cell carcinoma, in-situ cervical cancer).
• Major surgery within 4 weeks of starting the study
• Co-existing active infection or serious concurrent medical condition
• Significant cardiovascular disease
• Bone metastases
• Known brain or leptomeningeal metastases
• Surgery or hospital admissions for symptomatic intra-abdominal adhesions
• Active endoscopically proven peptic ulcer disease or colitis