Hydroxytyrosol for Colorectal Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: The Methodist Hospital Research Institute
Must be taking: 5FU-based therapy
Must not be taking: Corticosteroids, Immunosuppressants
Disqualifiers: Cardiac abnormalities, Hepatitis, HIV, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a phase I study investigating the safety and antitumor activity of 5FU-based therapy (FOLFIRI/FOLFOX + Biologics) in combination with Hydroxytyrosol (HT) as a treatment for patients with advanced or metastatic colorectal cancer.
Patients will receive: 1 capsule of HT 25 mg daily for 2 weeks before beginning 5FU-based therapy (FOLFIRI/FOLFOX + Biologics), 1 capsule of HT (25 mg) daily for 2 weeks while receiving the FOLFIRI/FOLFOX + Biologics, until sign of disease progression.
The prescribed FOLFIRI/FOLFOX administer as: Irinotecan 180 mg/m² intravenously (IV) over 90 minutes concurrently with Leucovorin 400 mg/m² IV over 120 minutes, followed by Fluorouracil 400-500 mg/m² IV bolus then 2400-3000 mg/m² IV infusion over 4-6 hours with or without, the designated Biologics, a standard dose of Cetuximab or Bevacizumab will be administered in 2-week cycles until disease progression or un-tolerated toxicity
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, it mentions that patients receiving certain treatments like corticosteroids or investigational agents may not be eligible, so it's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug Hydroxytyrosol for colorectal cancer?
Research shows that Hydroxytyrosol, a compound found in olive oil, can slow down the growth of cancer cells and trigger their self-destruction in colorectal cancer cell studies. It has also shown similar effects in other types of cancer, suggesting it might help fight cancer by stopping cell growth and promoting cell death.
12345Is hydroxytyrosol safe for human use?
Hydroxytyrosol, a compound found in olive oil, has been evaluated for safety, and a study suggests a No Observed Adverse Effects Level (NOAEL) of 500mg/kg/day, indicating it is generally safe at this dosage.
23467How is the drug Hydroxytyrosol unique in treating colorectal cancer?
Hydroxytyrosol, a compound found in olive oil, is unique because it acts as a powerful antioxidant and can induce cancer cell death (apoptosis) and inhibit cell growth in colorectal cancer. Unlike traditional treatments, it targets specific genes involved in cell death and has shown potential in various cancer types, making it a novel option for colorectal cancer therapy.
12348Eligibility Criteria
This trial is for patients with advanced or metastatic colorectal cancer. Participants must be suitable for 5FU-based therapy and able to take daily capsules of Hydroxytyrosol (HT). Specific inclusion and exclusion criteria are not provided, but typically involve factors like overall health, prior treatments, and the stage of cancer.Inclusion Criteria
I am fully active or can carry out light work.
My colorectal cancer is confirmed to be advanced or has spread.
Life expectancy ≥6 months
+5 more
Exclusion Criteria
I have hepatitis B, C, or HIV that is not under control.
Serum albumin <2.8 g/dL
Total bilirubin >1.5 × ULN or >1.5 mg/dL
+18 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Pre-treatment
Participants receive 1 capsule of HT 25 mg daily for 2 weeks before beginning 5FU-based therapy
2 weeks
1 visit (in-person)
Treatment
Participants receive 5FU-based therapy (FOLFIRI/FOLFOX + Biologics) in combination with HT until disease progression or un-tolerated toxicity
Up to 100 weeks
Bi-weekly visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 2 years
Participant Groups
The study tests the safety and effectiveness of adding HT to standard chemotherapy regimens (FOLFIRI/FOLFOX + Biologics) in treating colorectal cancer. Patients will take HT daily before and during their chemo cycles until disease progression or unacceptable side effects occur.
1Treatment groups
Experimental Treatment
Group I: Hydroxytyrosol (HT) in combination with Folfiri/FolfoxExperimental Treatment1 Intervention
Patients will receive: 1 capsule of HT 25 mg daily for 2 weeks before beginning 5FU-based therapy (FOLFIRI/FOLFOX + Biologics), 1 capsule of HT (25 mg) daily for 2 weeks while receiving the FOLFIRI/FOLFOX + Biologics, until sign of disease progression.
The prescribed FOLFIRI/FOLFOX administer as: Irinotecan 180 mg/m² intravenously (IV) over 90 minutes concurrently with Leucovorin 400 mg/m² IV over 120 minutes, followed by Fluorouracil 400-500 mg/m² IV bolus then 2400-3000 mg/m² IV infusion over 4-6 hours with or without, the designated Biologics, a standard dose of Cetuximab or Bevacizumab will be administered in 2-week cycles until disease progression or un-tolerated toxicity
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Houston Methodist.Houston, TX
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Who Is Running the Clinical Trial?
The Methodist Hospital Research InstituteLead Sponsor
References
High doses of hydroxytyrosol induce apoptosis in papillary and follicular thyroid cancer cells. [2018]Recent evidences indicates that hydroxytyrosol, one of the main olive oil phenols, possess antitumor effects because of its pro-oxidant properties and the capacity to inhibit proliferation and to promote apoptosis in several tumor cell lines, although most of the results were obtained for breast and digestive systems cancers.
Effects of Hydroxytyrosol on Expression of Apoptotic Genes and Activity of Antioxidant Enzymes in LS180 Cells. [2022]Label="PURPOSE" NlmCategory="OBJECTIVE">Colorectal cancer is the third-most commonly occurring cancer in developed countries. Hydroxytyrosol is a potent antioxidant that has several activities, such as oxidative-stress control, inhibition of cell proliferation, and induction of apoptosis. In this study, the effect of hydroxytyrosol on the expression of genes effective in apoptosis - BAX, BCL2, CASP3, P53, PPAR G, and NFE2L2 - and antioxidant-enzyme activity in LS180 cells of human colorectal cancer was investigated.
A Comparison of the Anti-Cancer Effects of Free and PLGA-PAA Encapsulated Hydroxytyrosol on the HT-29 Colorectal Cancer Cell Line. [2022]Hydroxytyrosol is one of the phenolic compounds of olive oil and can induce anticancer effects on colorectal cancer cells.
Hydroxytyrosol inhibits growth and cell proliferation and promotes high expression of sfrp4 in rat mammary tumours. [2015]Hydroxytyrosol (a phenolic compound derived from virgin olive oil) has demonstrated an anti-tumour effect in several tumour cell lines in addition to other health-related properties. The aim of this study was to investigate, for the first time in an animal model of experimental mammary carcinoma, the anti-cancer ability of hydroxytyrosol and to discover which pathways are modified by hydroxytyrosol.
Cancer chemoprevention by hydroxytyrosol isolated from virgin olive oil through G1 cell cycle arrest and apoptosis. [2019]Recent epidemiological evidence and animal studies suggest a relationship between the intake of olive oil and a reduced risk of several malignancies. The present study assesses the effect of hydroxytyrosol, a major antioxidant compound of virgin olive oil, on proliferation, apoptosis and cell cycle of tumour cells. Hydroxytyrosol inhibited proliferation of both human promyelocytic leukaemia cells HL60 and colon adenocarcinoma cells HT29 and HT29 clone 19A. The con-centrations of hydroxytyrosol which inhibited 50% of cell proliferation were approximately 50 and approximately 750 micromol/l for HL60 and both HT29 and HT29 clone 19A cells, respectively. At concentrations ranging from 50 to 100 micromol/l, hydroxytyrosol induced an appreciable apoptosis in HL60 cells after 24 h of incubation as evidenced by flow cytometry, fluorescence microscopy and internucleosomal DNA fragmentation. Interestingly, no effect on apoptosis was observed after similar treatment of freshly isolated human lymphocytes and polymorphonuclear cells. The DNA cell cycle analysis, quantified by flow cytometry, showed that the treatment of HL60 cells with hydroxytyrosol 50-100 micromol/l arrested the cells in the G0/G1 phase with a concomitant decrease in the cell percentage in the S and G2/M phases. These results support the hypothesis that hydroxytyrosol may exert a protective activity against cancer by arresting the cell cycle and inducing apoptosis in tumour cells, and suggest that hydroxytyrosol, an important component of virgin olive oil, may be responsible for its anticancer activity.
Toxicological evaluation of pure hydroxytyrosol. [2013]Of all the phenolic constituents of olives and extra virgin olive oil, hydroxytyrosol is currently being actively exploited as a potential supplement or preservative to be employed in the nutraceutical, cosmeceutical, and food industry. In terms of safety profile, hydroxytyrosol has only been investigated as the predominant part of raw olive mill waste water extracts, due to the previous unavailability of appropriate quantities of the pure compound. We report the toxicological evaluation of hydroxytyrosol and, based on the results, propose a No Observed Adverse Effects Level (NOAEL) of 500mg/kg/d.
Involvement of the PI3K/AKT Intracellular Signaling Pathway in the AntiCancer Activity of Hydroxytyrosol, a Polyphenol from Olea europaea, in Hematological Cells and Implication of HSP60 Levels in Its Anti-Inflammatory Activity. [2022]Hydroxytyrosol (HT), the main representative of polyphenols of olive oil, has been described as one of the most powerful natural antioxidants, also showing anti-inflammatory, antimicrobial, cardioprotective and anticancer activity in different type of cancers, but has been little studied in hematological neoplasms. The objective of this work was to evaluate the anticancer potential of HT in acute human leukemia T cells (Jurkat and HL60) and the anti-inflammatory potential in murine macrophages (Raw264.7). For this, cytotoxicity tests were performed for HT, showing IC50 values, at 24 h, for Jurkat, HL60 and Raw264.7 cells, of 27.3 µg·mL-1, 109.8 µg·mL-1 and 45.7 µg·mL-1, respectively. At the same time, HT caused cell arrest in G0/G1 phase in both Jurkat and HL60 cells by increasing G0/G1 phase and significantly decreasing S phase. Apoptosis and cell cycle assays revealed an antiproliferative effect of HT, decreasing the percentage of dividing cells and increasing apoptosis. Furthermore, HT inhibited the PI3K signaling pathway and, consequently, the MAPK pathway was activated. Inflammation tests revealed that HT acts as an anti-inflammatory agent, reducing NO levels in Raw264.7 cells previously stimulated by lipopolysaccharide (LPS). These processes were confirmed by the changes in the expression of the main markers of inflammation and cancer. In conclusion, HT has an anticancer and anti-inflammatory effect in the cell lines studied, which were Raw264.7, Jurkat, and HL60, and could be used as a natural drug in the treatment of liquid cancers, leukemias, myelomas and lymphomas.
Hydroxytyrosol Induces Apoptosis and Cell Cycle Arrest and Suppresses Multiple Oncogenic Signaling Pathways in Prostate Cancer Cells. [2018]Hydroxytyrosol (HT), a polyphenol from olives, is a potential anticancer agent. This study was designed to evaluate the anticancer activity of HT against prostate cancer cells, and the mechanism thereof.