All Trans Retinoic Acid Combined with Toripalimab+Chemotherapy for Locally Advanced Inoperable or Metastatic Triple Negative Breast Cancer：a Multi-center, Multi-cohort Phase II Trial

Trial Title: All Trans Retinoic Acid Combined with Toripalimab+Chemotherapy for Locally Advanced Inoperable or Metastatic Triple Negative Breast Cancer：a Multi-center, Multi-cohort Phase II Trial

NCT ID: NCT06636981

Condition: Triple Negative Breast Cancer (TNBC)

Conditions: Official terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Tretinoin

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Cohort2: ATRA+Toripalimab+TPC
Description: Receive 200 mg D1 of Toripalimab via intravenous infusion for a course of 21 days; TPC regimen (monoclonal antibody 10mg/kg D1, 8 intravenous infusions, 1 course of treatment every 21 days; Elibulin 1.4mg/m2 D1, 8 intravenous infusions, 1 course of treatment every 21 days; Utideron 40mg/m2 D1-5 intravenous infusions, 1 course of treatment every 21 days; Gemcitabine 1000mg/m2 D1, 8 intravenous infusions, 1 course of treatment every 21 days; Albumin paclitaxel 100 mg/m2 D1, D8, intravenous infusion, 1 course of treatment every 21 days); Capecitabine 1000mg/m2, D1-14, oral, one course of treatment every 21 days); All trans retinoic acid 20 mg bid, orally, D-3-D11, administered continuously for 14 days, stopped for 7 days, with one course of treatment lasting 21 days.
Arm group label: cohort2: ATRA+Toripalimab+TPC

Intervention type: Drug
Intervention name: Cohort1: ATRA+Toripalimab+chemo
Description: Receive 200 mg of Toripalimab via D1 intravenous infusion, with 21 days as one course of treatment; Albumin paclitaxel 100 mg/m2, D1, D8, intravenous infusion, one course of treatment for 21 days; All trans retinoic acid 20 mg bid, oral, D-3-D11, continuous administration for 14 days, cessation for 7 days, 21 days is one course of treatment.
Arm group label: cohort1: All trans retinoic acid+Toripalimab+Chemotherapy

Summary: All trans retinoic acid Combined with Toripalimab+Chemotherapy for Locally Advanced inoperable or Metastatic Triple Negative Breast Cancer：a multi-center, multi-cohort phase II trial

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. The subjects voluntarily participate and sign a written informed consent form; 2. Age ≥ 18 years old; 3. For locally advanced inoperable or metastatic breast cancer confirmed by histology (according to AJCC 8th edition staging), the histology and pathology clearly showed that ER, PR, Her-2 were negative. If there was metastatic lesion pathology, the metastatic lesion histology and pathology should prevail. The definition of ER and PR negativity is: IHC ER<1%, IHC PR<1%. Her-2 negativity is defined as: immunohistochemical detection of Her-2 (-) or (1+), Her-2 (2+) must undergo FISH testing and the result is negative, Her-2 (-) or (1+) can choose to undergo FISH testing and the result is negative; 4. According to RECIST 1.1 criteria for solid tumor evaluation, there must be at least one measurable lesion; 5. Cohort 1: For locally advanced non operable or metastatic TNBC that has not been previously treated, intravenous chemotherapy and anti-tumor therapy may be used during previous neoadjuvant and/or adjuvant therapy stages, provided that the interval between the end of neoadjuvant and/or adjuvant therapy and the occurrence of recurrence/metastasis is ≥ 12 months; Cohort 2: Local late stage inoperable or metastatic TNBC with previous treatment failures of at least one line or above; 6. All subjects should undergo tumor lesion biopsy during the screening period to obtain sufficient qualified tumor tissue specimens for retrospective biomarker analysis (including PD-L1 expression levels) in their cohort. If subjects are unable to undergo biopsy, they should provide tumor samples or unstained sections (3-5 μm) that have been fixed in formalin and embedded in paraffin (FFPE) closest to the start of the study treatment (up to 24 months) for corresponding biomarker analysis; 7. The main organ function is good, the relevant examination indicators within 14 days before treatment meet the following requirements: Without blood transfusion, platelet count ≥ 100 × 10^9/L, hemoglobin ≥ 90g/L, neutrophil count (ANC) ≥ 1.5 × 10^9/L AST and ALT ≤ 2.5 x upper limit of normal (ULN), ≤ 5 x ULN if liver metastasis is present, total bilirubin ≤ 1.5 x ULN, serum creatinine (Cr) ≤ 1.5 ULN, or creatinine clearance rate ≥ 60mL/min (Cockcroft Gault formula) 8. Expected survival period ≥ 3 months; 9. ECOG PS score: 0-1 points; 10. Non surgical sterilization, male patients with women of childbearing age or partners of childbearing age, are required to use a medically approved contraceptive measure (such as intrauterine device, contraceptive pill, or condom) during the study treatment period and within 6 months after the end of the study treatment period; Female patients of childbearing age who undergo non-surgical sterilization must have a negative serum HCG test within 72 hours prior to enrollment in the study. Exclusion Criteria: 1. Individuals who have previously been treated with PD-1 or PD-L1 monoclonal antibodies; Participants in cohort 1 who have previously used albumin paclitaxel; 2. Individuals known to be allergic to any of the drugs in the study; 3. Patients who have hypersensitivity reactions to other vitamin A drugs; 4. History of active autoimmune diseases requiring systemic treatment in the past 2 years (e.g. corticosteroids (dose ≤ 10mg/day, except for prednisone or other effective hormones) or immunosuppressive drugs); 5. Diagnosed with immune deficiency or undergoing systemic steroid therapy (excluding doses ≤ 10mg/day of prednisone or other effective hormones) or any other form of immunosuppressive therapy within 7 days prior to enrollment; 6. There are other known malignant tumors that have progressed or require active treatment in the past 5 years. Excluding malignant tumors that can be treated locally and have already been cured, such as skin basal cell carcinoma, skin squamous cell carcinoma, and cervical cancer in situ; 7. Known to have active central nervous system (CNS) metastases; 8. History of non infectious pneumonia requiring steroid hormone therapy; 9. Active infections require systematic treatment; 10. There are serious uncontrolled hypertension, diabetes and hyperlipidemia; 11. History of II-IV congestive heart failure or myocardial infarction within 6 months prior to enrollment; 12. Individuals who tested positive for HIV during screening; 13. Active hepatitis (hepatitis B reference: HBsAg positive and HBV DNA ≥ 500 IU/ml; hepatitis C reference: HCV antibody positive and HCV copy number>upper limit of normal value); 14. Individuals with other serious acute or chronic physiological or mental problems; 15. Accepting any medication that is prohibited from being used in combination with the investigational drug, unless the medication has been discontinued within 7 days prior to enrollment; 16. Lactating women; 17. Individuals who have participated in clinical trials of other anti-tumor drugs within the past four weeks; 18. Inability to swallow, intestinal obstruction, or other factors that affect medication administration and absorption; 19. Any situation that other researchers consider unsuitable for participation in this study.

Gender: Female

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Start date: October 10, 2024

Completion date: September 2029

Lead sponsor:
Agency: Fudan University
Agency class: Other

Source: Fudan University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06636981