- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01490996
Combining Curcumin With FOLFOX Chemotherapy in Patients With Inoperable Colorectal Cancer (CUFOX)
A Phase I/IIa Study Combining Curcumin (Curcumin C3-Complex, Sabinsa) With Standard Care FOLFOX Chemotherapy in Patients With Inoperable Colorectal Cancer.
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.
Study Overview
Status
Conditions
Intervention / Treatment
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
- 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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Leicester, United Kingdom, LE1 2WW
- Dept Oncology, Leicester Royal Infirmary
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Chemotherapy only
Patients receiving up to 12 cycles of therapy.
Standard care pathway management.
|
Standard care chemotherapy
Other Names:
|
Experimental: Chemotherapy plus curcumin
Patients taking daily oral curcumin for up to 12 cycles of therapy.
Standard care pathway management.
|
Daily oral capsule(s)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to 6 months
|
Efficacy in terms of disease response and survival
Time Frame: Up to 7 years
|
Response rate will be measured using RECIST.
Overall survival will be measured in months.
|
Up to 7 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Anne L Thomas, PhD FRCS, University of Leicester/University Hospitals Leicester
Publications and helpful links
General Publications
- Howells LM, Iwuji COO, Irving GRB, Barber S, Walter H, Sidat Z, Griffin-Teall N, Singh R, Foreman N, Patel SR, Morgan B, Steward WP, Gescher A, Thomas AL, Brown K. Curcumin Combined with FOLFOX Chemotherapy Is Safe and Tolerable in Patients with Metastatic Colorectal Cancer in a Randomized Phase IIa Trial. J Nutr. 2019 Jul 1;149(7):1133-1139. doi: 10.1093/jn/nxz029.
- James MI, Iwuji C, Irving G, Karmokar A, Higgins JA, Griffin-Teal N, Thomas A, Greaves P, Cai H, Patel SR, Morgan B, Dennison A, Metcalfe M, Garcea G, Lloyd DM, Berry DP, Steward WP, Howells LM, Brown K. Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy. Cancer Lett. 2015 Aug 10;364(2):135-41. doi: 10.1016/j.canlet.2015.05.005. Epub 2015 May 12.
- Irving GR, Iwuji CO, Morgan B, Berry DP, Steward WP, Thomas A, Brown K, Howells LM. Combining curcumin (C3-complex, Sabinsa) with standard care FOLFOX chemotherapy in patients with inoperable colorectal cancer (CUFOX): study protocol for a randomised control trial. Trials. 2015 Mar 24;16:110. doi: 10.1186/s13063-015-0641-1.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Neoplastic Processes
- Colorectal Neoplasms
- Neoplasm Metastasis
- Colonic Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Capecitabine
- Curcumin
Other Study ID Numbers
- 0225
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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