Colonic Cancer, Metastasis
Conditions
Keywords
Curcumin, Colorectal cancer, metastases, FOLFOX
Brief summary
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.
Detailed description
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: 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. Secondary objectives 1. To observe any changes to the neuropathic side-effects of chemotherapy. 2. To observe potential for efficacy in terms of disease response and survival. 3. 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.
Interventions
DRUGOral complex C3 curcumin + chemotherapy
Daily oral capsule(s)
Standard care chemotherapy
Sponsors
University of Leicester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Completion of dose escalation over 2 cycles of therapy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Completion of (or withdrawal from) chemotherapy | 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 in terms of disease response and survival | Up to 7 years | Response rate will be measured using RECIST. Overall survival will be measured in months. |
Countries
United Kingdom
Outcome results
None listed