Trial Title:
Curcumin Supplementation in Cervical Cancer
NCT ID:
NCT06080841
Condition:
Locally Advanced Cervical Cancer
Conditions: Official terms:
Uterine Cervical Neoplasms
Curcumin
Piperine
Conditions: Keywords:
curcumin
locally advanced cervical cancer
p53
apoptosis
chemoradiotherapy
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
A pilot study in adult women diagnosed with cervical cancer in locally advanced stages
(IB3-IVA), who are selected to undergo treatment with concomitant QT-RT followed by BT,
by the Functional Gynecology Oncology Unit of the National Cancer Institute.
The intervention will be supplementation with different doses of curcumin. Patients will
eat a standard diet according to their requirements. The aim is to describe the
expression of p53 protein levels and apoptosis in tumor cells from these patients.
Patients will be monitored by a nutritionist and receive the corresponding care from the
medical oncologist.
Sample size. Because this is a pilot study, the sample size will be at the researcher's
convenience; 5 patients per group, 30 patients with locally advanced cervical cancer, who
are candidates to receive standard treatment of concomitant chemoradiotherapy, followed
by brachytherapy.
Blood, urine, fecal, and cervicovaginal cytology samples will be collected.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Dietary Supplement
Intervention name:
Curcumin
Description:
Patients will receive capsules with curcumin C3 (Sabinsa Corp, NJ, USA) containing 1g of
curcumin. They will be instructed to consume orally 1 capsule with breakfast for group 1,
1 capsule with each meal for group 3, and 2 capsules with each food for group 5.
Arm group label:
Group 1
Arm group label:
Group 3
Arm group label:
Group 5
Intervention type:
Dietary Supplement
Intervention name:
Curcumin + Piperine
Description:
Patients will receive capsules with curcumin C3 (Sabinsa Corp, NJ, USA) containing 1g of
curcumin additioned with 5 mg of piperine. They will be instructed to consume orally 1
capsule with breakfast for group 2, 1 capsule with each meal for group 4, and 2 capsules
with each meal for group 6.
Arm group label:
Group 2
Arm group label:
Group 4
Arm group label:
Group 6
Summary:
Brief Summary.
The goal of this pilot study is to learn about the effect of curcumin supplementation in
locally advanced cervical cancer patients. The main questions it aims to answer are:
- Does curcumin supplementation increase the levels of p53 and apoptosis in tumor
cells from cervical cancer patients?
- At which dose of curcumin supplementation is the broader effect observed for p53
expression and apoptosis in tumor cells from cervical cancer patients?
- Are all doses safe for supplementation?
Participants will be asked to take curcumin tablets throughout their cancer treatment.
Researchers will compare 6 different groups, each group will receive a different dose of
curcumin with or without piperin, to see the dose with the broader effect and safety of
curcumin supplementation:
1. 1 g of curcumin
2. 1 g of curcumin + piperine
3. 3 g of curcumin
4. 3 g of curcumin + piperine
5. 6 g of curcumin
6. 6 g of curcumin + piperine
Detailed description:
BACKGROUND Cervical cancer (CC) continues to be a major public health problem in Mexico.
Today more than 4,000 women die each year from this disease, which requires implementing
strategies that can improve current treatments, particularly for locally advanced
disease. Today it is clear that persistent high-risk Human Papillomavirus infections are
the main risk factor for developing CC. At the National Cancer Institute of Mexico
(INCan), 80% of patients are diagnosed at locally advanced stages (IB3-IVA). The standard
treatment for these stages is concomitant chemoradiotherapy (CCRT) followed by
brachytherapy (BT).
p53 restricts tumor growth, promoting cell death and decreasing cell viability.
Activation of p53 is vital for CCRT-induced cytotoxicity, while inactivation of p53 has
been associated with resistance or insensitivity to treatment. Different nutraceuticals
such as berberine and curcumin can reactivate endogenous p53 and exhibit its effects in
CC. The E6 oncoprotein inactivates the p53 pathway in CC; therefore, the restoration of
p53 may be a promising therapeutic strategy.
The health benefits associated with consuming fruits, vegetables, teas, and spices are
due to the presence of phytochemicals. Diets characterized by regular consumption of
fruits and vegetables have been associated with a decrease in the risk of CC. A
particular group of phytochemicals of interest is polyphenols. The polyphenol curcumin is
considered safe and non-toxic by the FDA (Food and Drug Administration), and its
administration causes minimal low-grade adverse effects (mainly grade 1 diarrhea). Based
on clinical trials' safety and toxicity profile, a dose of up to 8000 mg/day of curcumin
can be considered safe.
The current information on the bioavailability of phytochemicals continues to be limited,
which places great importance on the exploration of polyphenols as possible new
therapeutics. However, the low bioavailability and complex metabolism linked to
polyphenols make it difficult to recommend a dose for daily consumption. The addition of
piperine to curcumin supplementation has been demonstrated to increase absorption in the
intestine.
Different biological effects have been associated with curcumin supplementation in cancer
patients. Patients with pancreatic cancer received oral administration of curcumin at a
dose of 8 g/day for eight months in combination with gemcitabine, which was well
tolerated and showed an improvement in overall survival. Curcumin activity was evaluated
in patients with metastatic colon cancer, finding that it was safe and tolerable in
combination with FOLFOX.
In locally advanced CC patients, the effect that curcumin has on the expression of p53 in
tumor cells has not been investigated, although in vitro studies have demonstrated its
effect on the inhibition of oncoproteins, such as E6, and the consequent stabilization of
p53, which makes CC cells more susceptible to being destroyed.
The present pilot study seeks to demonstrate that curcumin supplementation will regulate
molecular markers, such as p53 and apoptosis in tumor cells, which could provide the
basis to study further whether this modulation by curcumin leads to a greater
susceptibility of the tumor to standard cancer treatment and, therefore, a better
response to treatment.
METHODS The work will be carried out at the National Cancer Institute of Mexico (INCan)
in patients with locally advanced CC. Six supplementation groups will be included; in
three groups, curcumin will be administered in tablets in oral doses of 1, 3, and 6 g /
day respectively, and in the other three groups, curcumin will be administered in tablets
in oral doses of 1, 3, and 6 g / day respectively plus 5 mg of piperine/g of curcumin (to
facilitate the absorption of curcumin).
Invitation to the study protocol: Diagnosis will be confirmed in the INCan Functional
Gynecology Oncology Unit. The corresponding studies are carried out to corroborate that
the patient meets the inclusion criteria. On the day of the invitation to the patient,
the patient will be explained what the study consists of, and the Informed Consents will
be read. If the patient agrees to participate and signs the consent, she will be assigned
to the corresponding curcumin dose group.
The patients will be followed for four visits throughout the study: (1) 2 weeks before
the beginning of treatment; (2) at the beginning of CRT; (3) at the third cycle of CRT;
and (4) at BT.
Patients will be evaluated in 4 visits:
- Visit 1: Indications for a standard diet will be given according to the patient's
requirements. Curcumin will be provided to the patient, and instructions for its use
will be given according to the group to which she has been assigned. Urine and serum
samples will be collected. A cervical swab sample will be obtained.
- Visit 2: The day of initiation of treatment with concomitant CRT. Feces, urine, and
serum samples will be collected. A cervical swab sample will be obtained.
- Visit 3: Once the 3 CRT cycles have been completed. Feces, urine, and serum samples
will be collected. A cervical swab sample will be obtained.
- Visit 4: When starting treatment with BT. Urine and serum samples will be collected.
Biological samples:
Cervicovaginal cytologies will be taken at each visit. The samples will be analyzed by
flow cytometry to quantify p53 positive cells and annexin will be used to identify
apoptosis.
Adherence to supplementation will be monitored, bioavailability will be investigated,
gastrointestinal toxicity determined, and the safety of supplementation evaluated.
Gastrointestinal symptoms will be classified at each visit during treatment according to
common toxicity criteria (CTCAE v. 5). Liver function tests, renal function tests, blood
chemistry, and hematic biometry will be monitored to assess curcumin supplementation
safety. Stool, urine, and serum samples will be taken, from which the bioavailability of
curcumin will be assessed by liquid chromatography-electrospray ionization-mass
spectrometry. A comparative analysis of these variables will be made between the
different supplementation groups to establish the dose in which an impact on the
expression of p53 and apoptosis is observed.
Analysis of data:
Data will be analyzed using Statistica software, and graphs will be made in GraphPad
Prism. A single-factor repeated measures analysis will be performed with repeated
measures across all treatments. The analysis plan will consist of:
- Normality test. The Shapiro-Wilk test will be performed to know if the variables'
distribution is normal.
- Descriptive analysis. The distribution of the quantitative independent variables
will be determined using the Kolmogorov-Smirnov test. The mean ± standard deviation
will be reported for variables with normal distribution or median with 25th and 75th
percentiles for variables with free distribution.
- One-way or two-way ANOVA will be performed to determine the significance of
differences between groups, followed by Tukey's test for the significance of
differences. Confidence intervals will be constructed at 95%, and a value will be
declared statistically significant when p is <0.05.
- Multivariate analysis. The following tests will be used to determine if there are
differences between the patients who were supplemented with the different doses of
curcumin and those who also received piperine:
- Student's T test for quantitative variables with normal distribution.
- Mann Whitney U test for quantitative variables with free distribution or
ordinal variables.
- Chi-square test for dichotomous and polytomous variables.
EXPECTED RESULTS AND PERSPECTIVES The investigators expect that curcumin supplementation
will stabilize the expression of p53 and increase the apoptosis of tumor cells. The
investigators also expect that piperine will increase its absorption. In addition, a dose
in humans associated with the expression of p53 has not been reported, so this study will
allow the identification of the dose that favors said expression in humans. In addition
to its molecular effect, due to its antioxidant properties, the investigators expect that
patients will improve gastrointestinal symptoms associated with treatment with CCRT.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Understanding the nature of the study and giving a written consent report.
2. Women > 18 years old.
3. ECOG performance status: 0-2.
4. Be willing and able to comply with scheduled visits, treatment plans, and laboratory
tests.
5. Patients with a histological cervical cancer diagnosis: squamous cell,
adenosquamous, adenocarcinoma, and glassy cell carcinoma.
6. Classified with clinical stage IB3-IVA (FIGO 2018).
7. Candidates to receive concomitant QT-RT followed by BT.
8. With disease measurable by any imaging method (CT/MRI/PET-CT) according to RECIST v
1.1 criteria.
9. Patients without prior treatment based on QT-RT.
10. Hemoglobin ≥ 10 g/dL.
11. Leukocytes ≥ 4000/mm3.
12. Platelets ≥ 100,000/mm3.
13. Adequate liver function.
Exclusion Criteria:
1. Patients undergoing nutritional treatment or ingesting any dietary supplement,
including those containing turmeric or turmeric derivatives, ginger, or rhizome of
the turmeric family.
2. Patients with uncontrolled intercurrent diseases, including active infections that
contraindicate CT.
3. Patients receiving concomitant treatment with an experimental drug.
4. Patients with vesicovaginal or vesicorectal fistula are diagnosed.
5. Patients with previous or concomitant malignancy except non-melanoma skin carcinoma.
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Instituto Nacional de Cancerología
Address:
City:
Mexico City
Zip:
14080
Country:
Mexico
Status:
Recruiting
Contact:
Last name:
David Cantú, MD, PhD
Phone:
+525536935200
Phone ext:
201
Email:
dfcantu@gmail.com
Contact backup:
Last name:
Lucía Tapia
Phone:
+525536935200
Email:
lucyincan23@hotmail.com
Start date:
April 19, 2023
Completion date:
March 2025
Lead sponsor:
Agency:
National Institute of Cancerología
Agency class:
Other
Collaborator:
Agency:
Sabinsa Corporation
Agency class:
Industry
Source:
National Institute of Cancerología
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06080841
