Clinical trial NCT01490996: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Colonic Cancer
Metastasis
Keywords: Curcumin
Colorectal cancer
metastases
FOLFOX
Lead sponsor: University of Leicester
Sponsor class: OTHER
First posted: 2011-12-13
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Completion of dose escalation over 2 cycles of therapy
timeFrame: 1 year
Secondary outcomes:
measure: Completion of (or withdrawal from) chemotherapy
timeFrame: Up to 6 months
measure: Efficacy in terms of disease response and survival
timeFrame: Up to 7 years
Other outcomes:
Locations:
city: Leicester
country: United Kingdom
facility: Dept Oncology, Leicester Royal Infirmary
Study officials:
affiliation: University of Leicester/University Hospitals Leicester
name: Anne L Thomas, PhD FRCS
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.