Combining Curcumin With FOLFOX Chemotherapy in Patients With Inoperable Colorectal Cancer

Study Overview
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Brief Summary
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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
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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 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.

Official Title
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A Phase I/IIa Study Combining Curcumin (Curcumin C3-Complex, Sabinsa) With Standard Care FOLFOX Chemotherapy in Patients With Inoperable Colorectal Cancer.

Conditions
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Colonic Cancer, Metastasis

Intervention / Treatment
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* Drug: Oral complex C3 curcumin + chemotherapy
* Drug: Chemotherapy only


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Chemotherapy only<br>Patients receiving up to 12 cycles of therapy. Standard care pathway management. | Drug: Chemotherapy only<br>* Standard care chemotherapy<br>* Other names: FOLFOX (protocol includes changes to XELOX - capecitabine);|
| Experimental: Chemotherapy plus curcumin<br>Patients taking daily oral curcumin for up to 12 cycles of therapy. Standard care pathway management. | Drug: Oral complex C3 curcumin + chemotherapy<br>* Daily oral capsule(s)<br>* Other names: C3-complex curcumin (diferuloylmethane);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Completion of dose escalation over 2 cycles of therapy | 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. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Completion of (or withdrawal from) chemotherapy | 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. | Up to 6 months | 
| Efficacy in terms of disease response and survival | Response rate will be measured using RECIST. Overall survival will be measured in months. | Up to 7 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Curcumin, Colorectal cancer, metastases, FOLFOX