Combining Curcumin With FOLFOX Chemotherapy in Patients With Inoperable Colorectal Cancer

NCT ID: NCT01490996

Last Updated: 2020-01-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2017-05-31

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.

Conditions

Colonic Cancer; Metastasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chemotherapy only

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

Group Type: ACTIVE_COMPARATOR

Chemotherapy only

Intervention Type: DRUG

Standard care chemotherapy

Chemotherapy plus curcumin

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

Group Type: EXPERIMENTAL

Oral complex C3 curcumin + chemotherapy

Intervention Type: DRUG

Daily oral capsule(s)

Interventions

Oral complex C3 curcumin + chemotherapy

Daily oral capsule(s)

Intervention Type: DRUG

Chemotherapy only

Standard care chemotherapy

Intervention Type: DRUG

Other Intervention Names

C3-complex curcumin (diferuloylmethane); FOLFOX (protocol includes changes to XELOX - capecitabine)

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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Leicester

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anne L Thomas, PhD FRCS

Role: PRINCIPAL_INVESTIGATOR

University of Leicester/University Hospitals Leicester

Locations

Dept Oncology, Leicester Royal Infirmary

Leicester, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 31132111 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25979230 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25872567 (View on PubMed)

Other Identifiers

0225

Identifier Type: -

Identifier Source: org_study_id