Reverse Triple Negative Immune Resistant Breast Cancer

Overview

This is a Phase II, open-label, two-arm parallel study evaluating the efficacy and safety of combined treatment (sodium cromoglicate or choline) with immune checkpoint inhibitor in mTNBC (triple negative breast cancer) patients who progressed during previous immune checkpoint inhibitors.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: October 15, 2022

Detailed Description

This is a Phase II, open-label, two-arm parallel study evaluating the efficacy and safety of combined treatment (sodium cromoglicate or choline) with immune checkpoint inhibitors in metastatic TNBC(triple negative breast cancer) patients who progressed during or following previous immune checkpoint inhibitors. The investigators have achieved a breakthrough in FUTURE study with an ORR (objective response rate) reaching 52.6% in IM (immune-modulatory) subtype TNBC patients. Despite this, there are still some IM subtype patients resistant to immunotherapy. How to reverse immunotherapy resistance or how to increase the sensitivity of immunotherapy efficacy, has become an urgent clinical problem to be solved. The preclinical results of our center show that TMAO and choline play a potentially important role in regulating tumor immune microenvironment. Oral choline can improve TMAO content in mouse serum, play the role of activating anti-tumor immunity, improve immunotherapy efficacy. Preclinical studies of our center also show that sodium cromoglicate can enhance anti-tumor immune response by inhibiting the activation of mast cells, increase the infiltration and function of cytotoxic CD8+ T cells, inhibit the growth of tumors in mice, and enhance the efficacy of PD-1 inhibitors in mice. Based on preclinical studies, the investigators designed this study to enroll mTNBC patients who have progressed during or following immunotherapy, and to explore the efficacy of choline or sodium cromoglicate combined with immunotherapy at a clinical level, providing new strategies of combined treatment for TNBC patients.

Interventions

  • Drug: choline
    • choline 300mg tid or 500mg bid, p.o
  • Drug: PD-1 inhibitor and chemo
    • PD-1antibody SHR1210 200mg q2w chemo (same regimen in previous treatment)
  • Drug: Sodium Cromoglicate
    • Sodium Cromoglicate 200mg qid, p.o

Arms, Groups and Cohorts

  • Experimental: choline
    • choline with anti-PD-1 and chemo ( exactly same regimen in previous treatment)
  • Experimental: sodium cromoglicate
    • sodium cromoglicate with anti-PD-1 and chemo ( exactly same regimen in previous treatment)

Clinical Trial Outcome Measures

Primary Measures

  • Objective Response Rate (ORR)
    • Time Frame: Baseline until disease progression or loss of clinical benefit],assessed up to 6 months
    • The proportion of participants whose best outcome is complete remission or partial remission (according to RECIST1.1)

Secondary Measures

  • Disease Control Rate(DOR)
    • Time Frame: Baseline through end of study,assessed up to 6 months
    • Complete remission or partial remission or stable disease (according to RECIST1.1)
  • Progression Free Survival(PFS)
    • Time Frame: Randomization to death from any cause, through the end of study,assessed up to 6 months
    • time to progressive disease (according to RECIST1.1)
  • Overall Survival (OS)
    • Time Frame: Randomization to death from any cause, through the end of study,assessed up to 12 months
    • time to death due to any cause

Participating in This Clinical Trial

Inclusion Criteria

  • ECOG Performance Status of 0, 1, or 2 – Metastatic or locally advanced, histologically documented TNBC (absence of HER2, ER, and PR expression) – Radiologic/objective evidence of recurrence or disease progression after immunotherapy(combined with targeted therapy or chemo ) 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 – History of eosinophilosis or mastocytosis – 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

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Fudan University
  • Provider of Information About this Clinical Study
    • Principal Investigator: Zhimin Shao, Professor – Fudan University
  • Overall Official(s)
    • Zhimin Shao, Professor, Principal Investigator, Fudan U
  • Overall Contact(s)
    • Zhimin Shao, Professor, 08664175590, zhimingshao@yahoo.com

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