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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2012 by University of Leicester
Sponsor:
Information provided by (Responsible Party):
University of Leicester
ClinicalTrials.gov Identifier:
NCT01490996
First received: December 7, 2011
Last updated: June 23, 2014
Last verified: March 2012
  Purpose

Oral curcumin (complex C3, Sabinsa Corp, Utah) will be given to patients with inoperable colorectal liver 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.


Condition Intervention Phase
Colonic Cancer
Metastasis
Drug: Oral complex C3 curcumin + chemotherapy
Drug: Chemotherapy only
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/IIa Study Combining Curcumin (Curcumin C3-Complex, Sabinsa) With Standard Care FOLFOX Chemotherapy in Patients With Inoperable Colorectal Cancer.

Resource links provided by NLM:


Further study details as provided by University of Leicester:

Primary Outcome Measures:
  • Completion of dose escalation over 2 cycles of therapy [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    Response rate will be measured using RECIST. Overall survival will be measured in months.


Estimated Enrollment: 51
Study Start Date: February 2012
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Chemotherapy only
Patients receiving up to 12 cycles of therapy. Standard care pathway management.
Drug: Chemotherapy only
Standard care chemotherapy
Other Name: FOLFOX (protocol includes changes to XELOX - capecitabine)
Experimental: Chemotherapy plus curcumin
Patients taking daily oral curcumin for up to 12 cycles of therapy. Standard care pathway management.
Drug: Oral complex C3 curcumin + chemotherapy
Daily oral capsule(s)
Other Name: C3-complex curcumin (diferuloylmethane)

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 liver 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01490996

Contacts
Contact: Glen R Irving, MB ChB PhD 01162231852 girving@doctors.org.uk
Contact: William P Steward, FRCP PhD 01162587597 wps1@le.ac.uk

Locations
United Kingdom
Dept Oncology, Leicester Royal Infirmary Recruiting
Leicester, United Kingdom, LE1 2WW
Contact: Glen Irving       girving@doctors.org.uk   
Sub-Investigator: Glen R Irving, MB ChB         
Principal Investigator: William P Steward, PhD FRCP         
Sponsors and Collaborators
University of Leicester
Investigators
Principal Investigator: William P Steward, PhD FRCS University of Leicester/University Hospitals Leicester
  More Information

Additional Information:
No publications provided

Responsible Party: University of Leicester
ClinicalTrials.gov Identifier: NCT01490996     History of Changes
Other Study ID Numbers: UNOLE0225
Study First Received: December 7, 2011
Last Updated: June 23, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Leicester:
Curcumin
Colorectal cancer
metastases
FOLFOX

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Curcumin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 18, 2014