Combining Curcumin With FOLFOX Chemotherapy in Patients With Inoperable Colorectal Cancer - Full Text View

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:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Curcumin

U.S. FDA Resources

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:	January 2012
Estimated Study Completion Date:	January 2019
Estimated Primary Completion Date:	January 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

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.

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

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

Contacts

Contact: Glen R Irving, MB ChB	01162231852	grbi1@le.ac.uk
Contact: William P Steward, FRCP PhD	01162587597	wps1@le.ac.uk

Locations

United Kingdom
Dept Oncology, Leicester Royal Infirmary	Active, not recruiting
Leicester, United Kingdom, LE1 2WW

Sponsors and Collaborators

University of Leicester

Investigators

Principal Investigator:

William P Steward, PhD FRCS

University of Leicester/University Hospitals Leicester

More Information

Additional Information:

University Of Leicester, Department of Cancer Studies and Molecular medicine This link exits the ClinicalTrials.gov site

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:	December 9, 2011
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:

Colonic Neoplasms
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 May 19, 2013

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