Renaissance: Reverse Triple Negative Immune Resistant Breast Cancer

Sponsor
Fudan University (Other)
Overall Status
Recruiting
CT.gov ID
NCT05076682
Collaborator
(none)
20
1
2
8
2.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: choline
  • Drug: anti-PD-1 antibody and chemotherapy
  • Drug: Sodium Cromoglicate
Phase 2

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 (immunomodulatory) 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
20 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Reverse Triple Negative Immune Resistant Breast Cancer
Actual Study Start Date :
Jun 30, 2022
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Mar 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: choline

choline with anti-PD-1 immunotherapy

Drug: choline
choline 300mg tid or 500mg bid, p.o

Drug: anti-PD-1 antibody and chemotherapy
PD-1 antibody SHR1210 200mg q2w chemotherapy (whether and which should be given depends on the treatment regimen before enrollment)

Experimental: sodium cromoglicate

sodium cromoglicate with anti-PD-1 immunotherapy

Drug: anti-PD-1 antibody and chemotherapy
PD-1 antibody SHR1210 200mg q2w chemotherapy (whether and which should be given depends on the treatment regimen before enrollment)

Drug: Sodium Cromoglicate
Sodium Cromoglicate will be administered intranasally (nasal spray) (5 spray each nostril 4 times a day, 1 mg/spray)

Outcome Measures

Primary Outcome Measures

  1. Objective Response Rate (ORR) [Baseline until disease progression or loss of clinical benefit, assessed up to 6 months]

  2. Immune changes in peripheral blood [Baseline until disease progression or loss of clinical benefit, assessed up to 6 months]

Secondary Outcome Measures

  1. Disease Control Rate (DCR) [Baseline through end of study, assessed up to 6 months]

  2. Progression Free Survival (PFS) [Randomization to death from any cause, through the end of study,assessed up to 6 months]

  3. Safety and treatment-related AEs [Randomization to death from any cause, through the end of study,assessed up to 12 months]

  4. Biomarker analysis [Baseline until disease progression or loss of clinical benefit, assessed up to 6 months]

    Mast cell function will be measured in pretreatment tissues to predict therapy response

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Fudan University Shanghai Cancer Center Shanghai China 200032

Sponsors and Collaborators

  • Fudan University

Investigators

  • Principal Investigator: Zhimin Shao, Professor, Fudan U

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Zhimin Shao, Professor, Fudan University
ClinicalTrials.gov Identifier:
NCT05076682
Other Study ID Numbers:
  • 2107239-9
First Posted:
Oct 13, 2021
Last Update Posted:
Jul 13, 2022
Last Verified:
Jul 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Zhimin Shao, Professor, Fudan University
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 13, 2022