search
Back to results

Combining Curcumin With FOLFOX Chemotherapy in Patients With Inoperable Colorectal Cancer (CUFOX)

Primary Purpose

Colonic Cancer, Metastasis

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Oral complex C3 curcumin + chemotherapy
Chemotherapy only
Sponsored by
University of Leicester
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colonic Cancer focused on measuring Curcumin, Colorectal cancer, metastases, FOLFOX

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Dept Oncology, Leicester Royal Infirmary

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Chemotherapy only

Chemotherapy plus curcumin

Arm Description

Patients receiving up to 12 cycles of therapy. Standard care pathway management.

Patients taking daily oral curcumin for up to 12 cycles of therapy. Standard care pathway management.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Efficacy in terms of disease response and survival
Response rate will be measured using RECIST. Overall survival will be measured in months.

Full Information

First Posted
December 7, 2011
Last Updated
January 29, 2020
Sponsor
University of Leicester
search

1. Study Identification

Unique Protocol Identification Number
NCT01490996
Brief Title
Combining Curcumin With FOLFOX Chemotherapy in Patients With Inoperable Colorectal Cancer
Acronym
CUFOX
Official Title
A Phase I/IIa Study Combining Curcumin (Curcumin C3-Complex, Sabinsa) With Standard Care FOLFOX Chemotherapy in Patients With Inoperable Colorectal Cancer.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
May 31, 2017 (Actual)
Study Completion Date
May 31, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Leicester

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colonic Cancer, Metastasis
Keywords
Curcumin, Colorectal cancer, metastases, FOLFOX

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Chemotherapy only
Arm Type
Active Comparator
Arm Description
Patients receiving up to 12 cycles of therapy. Standard care pathway management.
Arm Title
Chemotherapy plus curcumin
Arm Type
Experimental
Arm Description
Patients taking daily oral curcumin for up to 12 cycles of therapy. Standard care pathway management.
Intervention Type
Drug
Intervention Name(s)
Oral complex C3 curcumin + chemotherapy
Other Intervention Name(s)
C3-complex curcumin (diferuloylmethane)
Intervention Description
Daily oral capsule(s)
Intervention Type
Drug
Intervention Name(s)
Chemotherapy only
Other Intervention Name(s)
FOLFOX (protocol includes changes to XELOX - capecitabine)
Intervention Description
Standard care chemotherapy
Primary Outcome Measure Information:
Title
Completion of dose escalation over 2 cycles of therapy
Description
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Completion of (or withdrawal from) chemotherapy
Description
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.
Time Frame
Up to 6 months
Title
Efficacy in terms of disease response and survival
Description
Response rate will be measured using RECIST. Overall survival will be measured in months.
Time Frame
Up to 7 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne L Thomas, PhD FRCS
Organizational Affiliation
University of Leicester/University Hospitals Leicester
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dept Oncology, Leicester Royal Infirmary
City
Leicester
ZIP/Postal Code
LE1 2WW
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
31132111
Citation
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.
Results Reference
derived
PubMed Identifier
25979230
Citation
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.
Results Reference
derived
PubMed Identifier
25872567
Citation
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.
Results Reference
derived
Links:
URL
http://www2.le.ac.uk/departments/csmm
Description
University Of Leicester, Department of Cancer Studies and Molecular medicine

Learn more about this trial

Combining Curcumin With FOLFOX Chemotherapy in Patients With Inoperable Colorectal Cancer

We'll reach out to this number within 24 hrs