Colonic CancerPhase 1/2CUFOXNCT01490996
Combining Curcumin With FOLFOX Chemotherapy in Patients With Inoperable Colorectal Cancer
A Phase 1/2 study testing Oral complex C3 curcumin + chemotherapy and Chemotherapy only in people with Colonic Cancer and Metastasis, run by University of Leicester at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colonic Cancer, Metastasis
- What is being tested?
- Oral complex C3 curcumin + chemotherapy and Chemotherapy only
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Feb 2012to 31 May 2017
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- Willing to use contraception if applicable
- Informed consent
- Life expectancy estimated to be more than 12 weeks
Who cannot join
- 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).
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- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Dept Oncology, Leicester Royal Infirmary
Leicester, LE1 2WW
About this study
Official title: A Phase I/IIa Study Combining Curcumin (Curcumin C3-Complex, Sabinsa) With Standard Care FOLFOX Chemotherapy in Patients With Inoperable Colorectal Cancer.
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.
Read the 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:
- 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.
- Conditions
- Colonic Cancer, Metastasis
- Being tested
- Oral complex C3 curcumin + chemotherapy, Chemotherapy only
- Keywords
- Curcumin, Colorectal cancer, metastases, FOLFOX
- Medical subject headings
- Colonic Neoplasms, Neoplasm Metastasis, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral complex C3 curcumin + chemotherapyDrug
Also called C3-complex curcumin (diferuloylmethane)
Daily oral capsule(s)
Chemotherapy onlyDrug
Also called FOLFOX (protocol includes changes to XELOX - capecitabine)
Standard care chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| Chemotherapy only | Active comparator | Patients receiving up to 12 cycles of therapy. Standard care pathway management. Receives: Drug: Chemotherapy only |
| Chemotherapy plus curcumin | Experimental | Patients taking daily oral curcumin for up to 12 cycles of therapy. Standard care pathway management. Receives: Drug: Oral complex C3 curcumin + chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Completion of dose escalation over 2 cycles of therapy
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.
Measured: 1 year
Secondary outcomes (2)
Completion of (or withdrawal from) chemotherapy
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.
Measured: Up to 6 months
Efficacy in terms of disease response and survival
Response rate will be measured using RECIST. Overall survival will be measured in months.
Measured: Up to 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2011 (estimated)
- Study startFeb 2012
- Primary completion31 May 2017
- Study completion31 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Colonic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Leicester
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anne L Thomas, PhD FRCS, Principal investigator, University of Leicester/University Hospitals Leicester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01490996
- Sponsor's protocol ID
- 0225
- Acronym
- CUFOX
- Status last verified
- May 2017
- First submitted
- 7 Dec 2011
- Last updated
- 31 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 31132111James 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.
PubMed 25979230Irving 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.
PubMed 25872567
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIa Study Combining Curcumin (Curcumin C3-Complex, Sabinsa) With Standard Care FOLFOX Chemotherapy in Patients With Inoperable Colorectal Cancer.
- ClinicalTrials.gov ID
- NCT01490996
- Acronym / sponsor ID
- CUFOX / 0225
- Conditions
- Colonic Cancer, Metastasis
- Keywords
- Curcumin, Colorectal cancer, metastases, FOLFOX
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- University of LeicesterUniversity, hospital or other
- Study start
- Feb 2012
- Primary completion
- 31 May 2017 (actual)
- Study completion
- 31 May 2017 (actual)
- First posted
- 13 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chemotherapy only | Active comparator | Drug: Chemotherapy onlyPatients receiving up to 12 cycles of therapy. Standard care pathway management. |
| Chemotherapy plus curcumin | Experimental | Drug: Oral complex C3 curcumin + chemotherapyPatients taking daily oral curcumin for up to 12 cycles of therapy. Standard care pathway management. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral complex C3 curcumin + chemotherapyAlso: C3-complex curcumin (diferuloylmethane)Daily oral capsule(s) | Drug | Chemotherapy plus curcumin |
| Chemotherapy onlyAlso: FOLFOX (protocol includes changes to XELOX - capecitabine)Standard care chemotherapy | Drug | Chemotherapy only |
Primary outcome
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.
2 secondary outcomes
Completion of (or withdrawal from) chemotherapy
Time frame: Up to 6 months
Efficacy in terms of disease response and survival
Time frame: Up to 7 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2020.
- Derived from this study: PubMed 31132111Howells 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.
- Derived from this study: PubMed 25979230James 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.
- Derived from this study: PubMed 25872567Irving 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne L Thomas, PhD FRCS principal investigator
University of Leicester/University Hospitals Leicester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Oral complex C3 curcumin + chemotherapy and Chemotherapy only in people with Colonic Cancer and Metastasis, run by University of Leicester at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Completion of dose escalation over 2 cycles of therapy (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01490996, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2020.