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

• ClinicalTrials.gov Identifier: NCT01490996
• Recruitment Status: Unknown
• First Posted: December 13, 2011
• Last Update Posted: May 24, 2017
• Sponsor: University of Leicester
• Information provided by (Responsible Party): University of Leicester

Tracking Information

• First Submitted Date: December 7, 2011
• First Posted Date: December 13, 2011
• Last Update Posted Date: May 24, 2017
• Study Start Date: February 2012
• Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 9, 2011)

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.

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT01490996 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: December 9, 2011)

• 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.
• Efficacy [ Time Frame: Up to 7 years ]
  Response rate will be measured using RECIST. Overall survival will be measured in months.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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

1. To observe any changes to the neuropathic side-effects of chemotherapy.
2. To observe potential for efficacy in terms of disease response and survival.
3. 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: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Colonic Cancer
• Metastasis

Intervention

• Drug: Oral complex C3 curcumin + chemotherapy
  Daily oral capsule(s)
  Other Name: C3-complex curcumin (diferuloylmethane)
• Drug: Chemotherapy only
  Standard care chemotherapy
  Other Name: FOLFOX (protocol includes changes to XELOX - capecitabine)

Study Arms

• Active Comparator: Chemotherapy only
  Patients receiving up to 12 cycles of therapy. Standard care pathway management.
  Intervention: Drug: Chemotherapy only
• Experimental: Chemotherapy plus curcumin
  Patients taking daily oral curcumin for up to 12 cycles of therapy. Standard care pathway management.
  Intervention: Drug: Oral complex C3 curcumin + chemotherapy

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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: December 9, 2011): 51
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2019
• Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT01490996
• Other Study ID Numbers: UNOLE0225
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: University of Leicester
• Study Sponsor: University of Leicester
• Collaborators: Not Provided

Investigators

• Principal Investigator: Anne L Thomas, PhD FRCS; University of Leicester/University Hospitals Leicester

• PRS Account: University of Leicester
• Verification Date: May 2017