Evaluation of Curcumin Supplementation on p53 Levels and Apoptosis in Tumor Cells From Patients With Locally Advanced Cervical Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- p53 expression
研究概览
简要总结
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 g of curcumin
- 1 g of curcumin + piperine
- 3 g of curcumin
- 3 g of curcumin + piperine
- 6 g of curcumin
- 6 g of curcumin + piperine
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Understanding the nature of the study and giving a written consent report.
- •Women > 18 years old.
- •ECOG performance status: 0-
- •Be willing and able to comply with scheduled visits, treatment plans, and laboratory tests.
- •Patients with a histological cervical cancer diagnosis: squamous cell, adenosquamous, adenocarcinoma, and glassy cell carcinoma.
- •Classified with clinical stage IB3-IVA (FIGO 2018).
- •Candidates to receive concomitant QT-RT followed by BT.
- •With disease measurable by any imaging method (CT/MRI/PET-CT) according to RECIST v 1.1 criteria.
- •Patients without prior treatment based on QT-RT.
- •Hemoglobin ≥ 10 g/dL.
- •Leukocytes ≥ 4000/mm
- •Platelets ≥ 100,000/mm
- •Adequate liver function.
排除标准
- •Patients undergoing nutritional treatment or ingesting any dietary supplement, including those containing turmeric or turmeric derivatives, ginger, or rhizome of the turmeric family.
- •Patients with uncontrolled intercurrent diseases, including active infections that contraindicate CT.
- •Patients receiving concomitant treatment with an experimental drug.
- •Patients with vesicovaginal or vesicorectal fistula are diagnosed.
- •Patients with previous or concomitant malignancy except non-melanoma skin carcinoma.
结局指标
主要结局
p53 expression
时间窗: Through study completion, an average of 3 years
Using the liquid-based cervicovaginal cytology samples, p53 will be quantified by the ELISA method. p53 positive cells will be quantified through flow cytometry.
Frequency of Apoptosis
时间窗: Through study completion, an average of 3 years
A conjugate of Annexin V and fluorophore will be used to determine apoptosis in cells from liquid-based cytology, through flow cytometry. The number of apototic cells (positive for Annexin V) will be quantified, and the percentage will be calculated.
次要结局
- Frequency of Gastrointestinal toxicity(Through study completion, an average of 3 years)
- Bioavailability of curcumin(Through study completion, an average of 3 years)