Condition category
Cancer
Date applied
28/10/2011
Date assigned
28/10/2011
Last edited
01/12/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Mr Glen Irving

ORCID ID

Contact details

Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom
+44 116 252 2959
grbi1@leicester.ac.uk

Additional identifiers

EudraCT number

2011-002289-19

ClinicalTrials.gov number

Protocol/serial number

10672

Study information

Scientific title

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

Acronym

FOLFOX plus curcumin in patients with inoperable colorectal cancer

Study hypothesis

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

East Midlands (Derby 1) regional ethics committee , 04/08/2011, ref: 11/EM/0263

Study design

Randomised; Interventional and Observational; Design type: Treatment, Case-controlled study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Condition

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 names

Folinic acid, fluorouracil, oxaliplatin, curcumin

Primary outcome measures

Safety; Timepoint(s): Real-time adverse event reporting using Common Terminology Criteria for Adverse Events (CTC-AE), diaries and direct consultation.

Secondary outcome measures

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

Overall trial start date

09/01/2012

Overall trial end date

09/01/2015

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 51; UK Sample Size: 51

Participant 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

Recruitment start date

09/01/2012

Recruitment end date

09/01/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Leicester Royal Infirmary
Leicester
LE1 5WW
United Kingdom

Sponsor information

Organisation

University of Leicester (UK)

Sponsor details

Department of Cancer Studies and Molecular Medicine
Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Bowel Disease Research Foundation of ACPGBI (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Cancer Research UK (CRUK) (UK)

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

Hope Against Cancer (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Royal College of Surgeons of England (UK)

Alternative name(s)

RCS

Funding Body Type

private sector organisation

Funding Body Subtype

professional associations and societies

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2015 results in https://www.ncbi.nlm.nih.gov/pubmed/25872567

Publication citations

Additional files

Editorial Notes

01/12/2016: Publication reference added.