The Study of Quadruple Therapy Quercetin, Zinc, Metformin, and EGCG as Adjuvant Therapy for Early, Metastatic Breast Cancer and Triple-negative Breast Cancer, a Novel Mechanism

Triple Negative Breast Cancer Clinical Trial

Official title:

The Study of Quadruple Therapy Quercetin, Zinc, Metformin, and EGCG as Adjuvant Therapy for Early, Metastatic Breast Cancer and Triple-negative Breast Cancer, a Novel Mechanism

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05680662
• Other study ID #: Amr Ahmed
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: January 1, 2023
• Est. completion date: January 31, 2024

Study information

• Verified date: December 2022
• Source: Ministry of Health, Saudi Arabia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

breast cancer is the most common cancer in women. With more than 1 in 10 new cancer diagnoses each year, It is the second most frequent cancer-related death among women worldwide. Breast cancer develops slowly, and the majority of cases are found through routine screening.

breast cancer-causing deaths among women all over the world and increased in the last few years even though the treatment is advanced like immunotherapy chemotherapy by yet no treatment for triple-negative breast cancer zinc and competition between znt1 and zip6,10 at breast cancer cells. Is zinc ionophore like quercetin and EGCG has a role, In a novel experimental study zinc is a trace metal that has many roles in cells, enzymatic activity, and gene regulations, and also for the integrity of DNA.

Zinc transporters (zinc related -proteins such as ZIPs, and ZnTs are affected by triggers factors like cytokines and growth factors.

There are two large families of zinc transporters like ZIPs ( 14 members) and ZnTs family (10 members), ZIPS family cause an influx of zinc from the extracellular to the cytoplasm and also from intracellular organelles like endoplasmic reticulum or Golgi or mitochondria in contrast to ZnTs which cause an influx of zinc from the cytoplasm to intracellular organelles. ( lower cytoplasmic zinc) (1) Breast cancer deaths occurred from metastasis; Catalytic enzymes called proteases like cathepsin L are frequently overexpressed in aggressive cancers. Breast tumor metastatic potential is correlated with macrophage presence. These macrophages associated with tumors frequently adopt an M2-like pro-tumorigenic phenotype, which results in the production of growth hormones and proteases, notably the lysosomal protease cathepsin L. Because cathepsin L is commonly released by breast cancer cells and aids in tumor invasion, metastasis, and angiogenesis. It is expected that cathepsin L secretion by both tumor-associated macrophages and neoplastic cells would promote the metastatic phenotype because cathepsin L is widely produced by breast cancer cells and helps with tumor invasion, metastasis, and angiogenesis. (2) this study target new mechanisms and achieves the best management as some types of cancer breast like triple-negative breast cancer (TNBC) no definite treatment so we target the following pathways and epigenetic processes by these adjuvant compounds which have a promising role in the immunity like EGCG, Quercetin, Zinc, Metformin so our team will discuss novel methods to achieve the best efficacy from chemotherapy

Description:

breast cancer is the most common cancer in women. With more than 1 in 10 new cancer diagnoses each year, It is the second most frequent cancer-related death among women worldwide. Breast cancer develops slowly, and the majority of cases are found through routine screening.

breast cancer-causing deaths among women all over the world and increased in the last few years even though the treatment is advanced like immunotherapy chemotherapy by yet no treatment for triple-negative breast cancer zinc and competition between znt1 and zip6,10 at breast cancer cells. Is zinc ionophore like quercetin and EGCG has a role, In a novel experimental study zinc is a trace metal that has many roles in cells, enzymatic activity, and gene regulations, and also for the integrity of DNA.

Zinc transporters (zinc related -proteins such as ZIPs, and ZnTs are affected by triggers factors like cytokines and growth factors.

There are two large families of zinc transporters like ZIPs ( 14 members) and ZnTs family (10 members), ZIPS family cause an influx of zinc from the extracellular to the cytoplasm and also from intracellular organelles like endoplasmic reticulum or Golgi or mitochondria in contrast to ZnTs which cause an influx of zinc from the cytoplasm to intracellular organelles. ( lower cytoplasmic zinc) (1) Breast cancer deaths occurred from metastasis; Catalytic enzymes called proteases like cathepsin L are frequently overexpressed in aggressive cancers. Breast tumor metastatic potential is correlated with macrophage presence. These macrophages associated with tumors frequently adopt an M2-like pro-tumorigenic phenotype, which results in the production of growth hormones and proteases, notably the lysosomal protease cathepsin L. Because cathepsin L is commonly released by breast cancer cells and aids in tumor invasion, metastasis, and angiogenesis. It is expected that cathepsin L secretion by both tumor-associated macrophages and neoplastic cells would promote the metastatic phenotype because cathepsin L is widely produced by breast cancer cells and helps with tumor invasion, metastasis, and angiogenesis. (2) this study target new mechanisms and achieves the best management as some types of cancer breast like triple-negative breast cancer (TNBC) no definite treatment so we target the following pathways and epigenetic processes by these adjuvant compounds which have a promising role in the immunity like EGCG, Quercetin, Zinc, Metformin so our team will discuss novel methods to achieve the best efficacy from chemotherapy the study will include 100 cases with many types of breast cancer like hormonal sensitive, triple negative, and metastatic breast cancer, and another group of 100 patients not given this adjuvant therapy type of study is a randomized clinical control trial interventional with 4 compounds (EGCG,ZINC, QUERCETIN,METFORMIN)

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: January 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Age above 18

2. Female patients

3. with any type of breast cancer Ductal carcinoma in situ (DCIS) ... Invasive breast cancer (ILC or IDC) ... Triple-negative breast cancer. ... Inflammatory breast cancer. ... Paget disease of the breast. ... Angiosarcoma. ... Phyllodes tumor.

4. HER2-positive by ASCO CAP 2018 guidelines, confirmed by central testing

5. Participants must have normal organ and marrow function as defined below:

ANC = 1000/mm3 hemoglobin =8 g/dl platelets = 75,000/mm3 AST and ALT both <5x institutional ULN Total bilirubin = 1.5 mg/dL. For patients with Gilbert syndrome, the direct bilirubin should be <institutional ULN Serum creatinine = 2.0 mg/dL OR calculated GFR = 30mL/min 6- Locally advanced tumors at diagnosis, including tumors fixed to the chest wall, peau d'orange, skin ulcerations/nodules, or clinical inflammatory changes (diffuse brawny cutaneous induration with an erysipeloid edge) Patients with a history of previous invasive breast cancer.

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Exclusion Criteria:

Neoadjuvant or adjuvant chemotherapy for this breast cancer prior to enrollment is prohibited.

Any of the following due to teratogenic potential of the study drugs:

Pregnant women Nursing women Women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragms, IUDS, surgical sterilization, abstinence, etc). Hormonal birth control methods are not permitted.

Participants who are receiving any other investigational agents for treatment of breast cancer, unless specific approval is obtained from the Sponsor-Investigator.

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Related Conditions & MeSH terms

• Breast Cancer Female
• Breast Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Combination Product:
• quercetin, EGCG, metformin , zinc
this intervention target many mechanisms at tumorigenesis, metastasis autophagy, apoptosis, interleukin 6, cathepsin L, and also epigenetic DNA methylation

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Ministry of Health, Saudi Arabia

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	invasive Disease Free Survival at 3 Years from the time of randomization until the occurrence of the first of the following events: invasive local/regional recurrence, Contralateral invasive breast cancer, Distant recurrence, Death from any cause	Kaplan-Meier estimates of iDFS will be estimated and plotted with the corresponding 95% confidence intervals.; from the time of randomization until the occurrence of the first of the following events: invasive local/regional recurrence, Contralateral invasive breast cancer, Distant recurrence, Death from any cause	Time Frame: 3 Years
Secondary	Invasive Disease Free Survival at 10 Years	Kaplan-Meier estimates of iDFS will be estimated and plotted with the corresponding 95% confidence intervals.; from the time of randomization until the occurrence of the first of the following events: invasive local/regional recurrence, Contralateral invasive breast cancer, Distant recurrence, Death from any cause	10 years
Secondary	Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0 [	NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for AE reporting	5 years
Secondary	Total patient chair time of drug administration	Mean difference will be estimated between HP FDC SC and IV admin of HP in sub-study	18 months
Secondary	Breast cancer-specific survival (BCSS) at 10 Years	the time period between randomization and death due to breast cancer.	10 years