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

NCT05680662 | Unknown Early Phase 1 DMC FDA Drug

• 1 other identifier: Amr Ahmed
• Study Type: interventional
• Target: 200
• Locations: 0 countries
• Sites: N/A

Brief 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

Conditions

Breast Cancer Female; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Invasive Disease Free Survival at 10 Years

  10 years

• Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0 [

  5 years

• Total patient chair time of drug administration

  18 months

• Breast cancer-specific survival (BCSS) at 10 Years

  10 years

Study Arms (2)

adjuvant quadruple thearpy of quercetin , zinc, EGCG, metformin for 100 breast cancer cases

EXPERIMENTAL

experimental study of adjuvant quadruple therapy of quercetin, zinc, EGCG, and metformin for 100 cases of different types of breast cancer women daily dose as follows daily 500 mg orally quercetin OD daily 50 mg zinc sulfate orally OD daily 300 mg EGCG orally OD daily metformin 850 mg orally OD during chemotherapy courses and until last stage of treatment

Combination Product: quercetin, EGCG, metformin , zinc

no adjuvant thearpy for 100 cases of breast cancer breast for this group ( controlled group )

EXPERIMENTAL

this arm ( 100 cases controlled group not taken adjuvant therapy only was taken the regular chemotherapy as prescription

Combination Product: quercetin, EGCG, metformin , zinc

Interventions

quercetin, EGCG, metformin , zinc COMBINATION_PRODUCT

this intervention target many mechanisms at tumorigenesis, metastasis autophagy, apoptosis, interleukin 6, cathepsin L, and also epigenetic DNA methylation

adjuvant quadruple thearpy of quercetin , zinc, EGCG, metformin for 100 breast cancer cases; no adjuvant thearpy for 100 cases of breast cancer breast for this group ( controlled group )

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age above 18
• Female patients
• 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.
• HER2-positive by ASCO CAP 2018 guidelines, confirmed by central testing
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ministry of Health, Saudi Arabia: lead

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Quercetin; epigallocatechin gallate; Metformin; Zinc

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Flavonols; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Biguanides; Guanidines; Amidines; Organic Chemicals; Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Amr Ahmed

Study Record Dates

• First Submitted: December 23, 2022
• First Posted: January 11, 2023
• Study Start: January 1, 2023
• Primary Completion: December 31, 2023
• Study Completion: January 31, 2024
• Last Updated: January 11, 2023

Record last verified: 2022-12