A phase I/IIa study combining curcumin (Curcumin C3 Complex, Sabinsa) with standard care FOLFOX chemotherapy in patients with inoperable colorectal cancer

ISRCTN	ISRCTN58705307
DOI	https://doi.org/10.1186/ISRCTN58705307
ClinicalTrials.gov (NCT)	NCT01490996
Clinical Trials Information System (CTIS)	2011-002289-19
Protocol serial number	10672
Sponsor	University of Leicester (UK)
Funders	Bowel Disease Research Foundation of ACPGBI (UK), Cancer Research UK (CRUK) (UK), Hope Against Cancer (UK), Royal College of Surgeons of England (UK)

Submission date: 28/10/2011
Registration date: 28/10/2011
Last edited: 04/09/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://cancerhelp.cancerresearchuk.org/trials/trial-looking-at-curcumin-and-folfox-for-advanced-bowel-cancer

Contact information

Mr Glen Irving
Scientific

Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom

Phone	+44 116 252 2959
Email	grbi1@leicester.ac.uk

Study information

Primary study design	Interventional
Study design	Randomised; Interventional and Observational; Design type: Treatment, Case-controlled study
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A phase I/IIa study combining curcumin (Curcumin C3 Complex, Sabinsa) with standard care FOLFOX chemotherapy in patients with inoperable colorectal cancer
Study acronym	FOLFOX plus curcumin in patients with inoperable colorectal cancer
Study objectives	Phase I/IIa study administering daily oral C3-complex curcumin to patients receiving standard care folinic acid (FOL) fluorouracil (F) and Oxalipatin (OX) (FOLFOX) chemotherapy. Phase I is a dose-escalation response study to establish a maximum tolerated dose. Phase IIa is a two-armed control study comparing FOLFOX+curcumin with FOLFOX alone. The second phase is randomised. Between 42 and 51 patients will be recruited depending on dose-limiting toxicities observed in phase I. Treatment will last for up to 12 cycles (approx 6 months of chemotherapy). Recruitment is anticipated to take 3 years. Follow-up will include routine CT scans to monitor progression, and ultimately survival times. Median survival approx 18 months and <5% 5 year survival, therefore potential running time 7 years in the event of extremely favourable treatment response.
Ethics approval(s)	East Midlands (Derby 1) regional ethics committee , 04/08/2011, ref: 11/EM/0263
Health condition(s) or problem(s) studied	Topic: National Cancer Research Network; Subtopic: Colorectal Cancer; Disease: Colon
Intervention	This study is the first to combine daily oral curcumin with standard care FOLFOX-based (5-fluorouracil, folinic acid and oxaliplatin) chemotherapy in colorectal cancer patients with inoperable liver metastases: the CUFOX trial. CUFOX comprises a Phase 1 dose-escalation study (3 + 3 + 3 design) to determine an acceptable target dose of curcumin with which to safely proceed to a Phase IIa open-labelled randomised controlled trial. Thirty three participants with histological or cytological confirmation of inoperable colorectal cancer will then be randomised to oxaliplatin-based chemotherapy with the addition of daily oral curcumin at the target dose determined in Phase I, or to standard care oxaliplatin-based chemotherapy alone (recruiting at a ratio of 2:1).
Intervention type	Drug
Phase	Phase I/II
Drug / device / biological / vaccine name(s)	Folinic acid, fluorouracil, oxaliplatin, curcumin
Primary outcome measure(s)	Safety; Timepoint(s): Real-time adverse event reporting using Common Terminology Criteria for Adverse Events (CTC-AE), diaries and direct consultation.
Key secondary outcome measure(s)	1. Biomarker Discovery; Timepoint(s): Samples taken during treatment phase 1-2years. Analysis 3-4 years. 2. Efficacy; Timepoint(s): Measured by response (RECIST) and survival 3. Measurement of systemic curcumin; Timepoint(s): During treatment phase 4. Neurotoxic side-effects; Timepoint(s): 2 weekly neurotoxicity questionnaires 5. Tolerability/Establishing Target Dose; Timepoint(s): Completion dose escalation phase of 3 consecutive patients without dose-limiting toxicitiy 2 cycles
Completion date	09/01/2015

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	51
Total final enrolment	28
Key inclusion criteria	1. Histological or cytological diagnosis of metastatic colorectal cancer 2. Measurable disease by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) 3. Adequate haematological, hepatic and renal function 4. Age more than or equal to 18 years 5. Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1 6. Patients must have recovered from effects of any recent major surgery 7. Willing to use contraception if applicable 8. Informed consent 9. Life expectancy estimated to be more than 12 weeks; Target Gender: Male & Female ; Lower Age Limit 18 no age limit or unit specified
Key exclusion criteria	1.Contraindications to FOLFOX chemotherapy: Peripheral neuropathy National Cancer Institute Common Toxicity Criteria (NCI CTC) >1, Liver failure, uncontrolled coronary heart disease, myocardial infarction within the previous 6 months. 2. Unwilling or unable to comply with the study protocol 3. 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. 4. Undergone chemotherapy (other than adjuvant for CRC) or participating in another drug study. 5. Previous cancer <5 years (other than colorectal, basal cell carcinoma, in-situ cervical cancer) 6. Major surgery within 4 weeks of starting the study 7. Co-existing active infection or serious concurrent medical condition 8. Significant cardiovascular disease 9. Bone metastases 10. Known brain or leptomeningeal metastases 11. Surgery or hospital admissions for symptomatic intra-abdominal adhesions 12. Active endoscopically proven peptic ulcer disease or colitis
Date of first enrolment	09/01/2012
Date of final enrolment	09/01/2015

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Leicester Royal Infirmary

Leicester
LE1 5WW
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/07/2019	04/09/2019	Yes	No
Protocol article	protocol	24/03/2015		Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

04/09/2019: ClinicalTrials.gov number, publication reference and total final enrolment number added.
01/12/2016: Publication reference added.