Dasatinib Combined With Quercetin to Reverse Chemo Resistance in Triple Negative Breast Cancer

a Pilot Study to Explore the Efficacy and Safety of Dasatinib Combined With Quercetin to Reverse Chemotherapy Resistance in Triple Negative Breast Cancer.

This is a Phase II, open-label, single-arm study evaluating the efficacy and safety of combined treatment of dasatinib, quercetin with chemotherapy in mTNBC (triple negative breast cancer) patients who progressed during previous chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Triple-negative Breast Cancer
• Intervention / Treatment: Drug: Taxane/Anthracycline/Eribulin Mesylate/Vinorelbine/Capecitabine/Carboplatin/UTD1/platinum; Drug: Quercetin; Drug: Dasatinib

Detailed Description

This is a Phase II, open-label, single-arm study evaluating the efficacy and safety of combined treatment of dasatinib, quercetin with chemotherapy in mTNBC (triple negative breast cancer) patients who progressed during previous chemotherapy. Chemotherapy is the backbone drug for TNBC. How to reverse chemotherapy resistance or how to increase the sensitivity of chemotherapy efficacy, has become an urgent clinical problem to be solved. Our preclinical studies have demonstrated that the combination of dasatinib and quercetin with chemotherapy can effectively eliminate chemotherapy-induced senescent fibroblasts, decrease the proliferation rate of disseminated tumor cells, and ultimately lead to a significant reduction in metastasis and recurrence, thereby enhancing the efficacy of chemotherapy. Based on preclinical studies, the investigators designed this study to enroll mTNBC patients who have progressed during or following chemotherapy, and to explore the efficacy of combined treatment of dasatinib, quercetin with chemotherapy at a clinical level, providing new strategies of combined treatment for TNBC patients.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yin Liu, MD; Phone Number: +8664175590; Email: liuyinfudan@163.com
• Study Contact Backup: Name: Zhimin Shao, MD, PhD; Phone Number: +8664175590; Email: zhimingshao@yahoo.com

Study Locations

• China
  • Shanghai, China, 200032
    • Recruiting
    • 270 Dongan Road, Fudan University Shanghai Cancer Center
    • Contact: Yin Liu, MD; Phone Number: +8664175590; Email: liuyinfudan@163.com
    • Contact: Zhimin Shao, MD, PhD; Phone Number: +8664175590

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ECOG Performance Status of 0, 1
• Metastatic or locally advanced, histologically documented TNBC (absence of HER2, ER, and PR expression)
• Radiologic/objective evidence of recurrence or disease progression after chemotherapy for metastatic breast cancer (MBC)
• Adequate hematologic and end-organ function, laboratory test results, obtained within 14 days prior to initiation of study treatment.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures as outlined for each specific treatment arm
• Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1)
• have the cognitive ability to understand the protocol and be willing to participate and to be followed up

Exclusion Criteria:

• Symptomatic, untreated, or actively progressing CNS metastases
• Active or history of autoimmune disease or immune deficiency
• Significant cardiovascular disease
• History of malignancy other than breast cancer within 5 years prior to screening, with the exception of those with a negligible risk of metastasis or death
• Treatment with chemotherapy, radiotherapy,immunotherapy or surgery (outpatient clinic surgery excluded) within 3 weeks prior to initiation of study treatment.
• Pregnancy or breastfeeding, or intention of becoming pregnant during the study
• History of allergies to the drug components of this trial
• Patients who have been using oral steroid hormones for a long time will need to stop for 4 weeks if they have used them occasionally in the past

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: quercetin and dasatinib	Drug: Taxane/Anthracycline/Eribulin Mesylate/Vinorelbine/Capecitabine/Carboplatin/UTD1/platinum; Taxane/Anthracycline/Eribulin Mesylate/Vinorelbine/Capecitabine/Carboplatin/UTD1/platinum; Drug: Quercetin; quercetin 1000mg d1-d3, qw; Drug: Dasatinib; Dasatinib 50mg d1-d3, qw

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR)	Baseline until disease progression or loss of clinical benefit, assessed up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR)		Baseline through end of study, assessed up to 6 months
Progression Free Survival (PFS)		Randomization to death from any cause, through the end of study,assessed up to 6 months
Safety and treatment-related AEs		Randomization to death from any cause, through the end of study,assessed up to 12 months
Biomarker analysis1	the pre- and post-treatment levels of age-related secretory factors and neutrophil extracellular traps in serum and lung puncture samples.	Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
Biomarker analysis2	Immunohistochemical staining of tissue sections before and after treatment including number of senescent fibroblasts, number and area of neutrophil extracellular traps.	Baseline until disease progression or loss of clinical benefit, assessed up to 6 months

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): January 31, 2025

Study Registration Dates

• First Submitted: March 30, 2024
• First Submitted That Met QC Criteria: April 6, 2024
• First Posted (Actual): April 9, 2024

Study Record Updates

• Last Update Posted (Actual): July 8, 2024
• Last Update Submitted That Met QC Criteria: July 5, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Antioxidants; Tyrosine Kinase Inhibitors; Carboplatin; Capecitabine; Vinorelbine; Taxane; Dasatinib; Quercetin
• Other Study ID Numbers: B2024.1.30

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No