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Inosine Reverse Chemo Resistance in Triple Negative Breast Cancer

Phase 2
Not yet recruiting
Conditions
Triple-negative Breast Cancer
Interventions
Drug: Taxane/Anthracycline/Eribulin Mesylate/Vinorelbine/Capecitabine/Carboplatin/UTD1/platinum
Registration Number
NCT06355024
Lead Sponsor
Fudan University
Brief Summary

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

Detailed Description

This is a Phase II, open-label, single-arm study evaluating the efficacy and safety of combined treatment of Inosine with chemotherapy in metastatic TNBC (triple negative breast cancer) patients who progressed during or following 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. The preclinical results show that Inosine play a potentially important role in regulating the tumor microenvironment. The investigators found that inosine from intestinal probiotics was negatively correlated with breast cancer recurrence and metastasis after chemotherapy, and further functional experiments showed that inosine-producing flora or dietary supplementation with inosine could significantly inhibit the survival of tumor cells after chemotherapy and inhibit the recurrence and metastasis of breast cancer. Furthermore, it is considered to have a high level of safety. 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 inosine with chemotherapy at a clinical level, providing new strategies of combined treatment for TNBC patients.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
Female
Target Recruitment
10
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
InosineTaxane/Anthracycline/Eribulin Mesylate/Vinorelbine/Capecitabine/Carboplatin/UTD1/platinumoral inosine arm
InosineInosineoral inosine arm
Primary Outcome Measures
NameTimeMethod
Objective Response Rate (ORR)Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
Secondary Outcome Measures
NameTimeMethod
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
Biomarker analysis1Baseline until disease progression or loss of clinical benefit, assessed up to 6 months

The distribution of immune cells in pre- and post-treatment blood samples, alterations in gut microbiota in fecal samples, the infiltration of immune cells, and the proliferation and apoptosis of tumor cells in metastatic puncture samples.

Safety and treatment-related AEsRandomization to death from any cause, through the end of study,assessed up to 12 months
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