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Treatment of triple-negative breast cancer (TNBC) remains a significant challenge. Although immune checkpoint inhibitors combined with chemotherapy have achieved breakthroughs, drug resistance persists, leaving clinical needs unmet. Bisphosphonates target the FDPS/mevalonate pathway, not only directly inhibiting tumors but also remodeling the immune microenvironment, positioning them as a potential strategy to reverse immune resistance. Therefore, this exploratory study of camrelizumab combined with risedronate sodium and chemotherapy aims to generate synergistic anti-tumor effects through the dual action of immune checkpoint blockade and metabolic-immune microenvironment remodeling. The goal is to overcome resistance, improve the objective response rate, and ultimately enhance the long-term survival prognosis for patients with TNBC.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Group | Experimental | Camrelizumab + Risedronate Sodium + Chemotherapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Camrelizumab + Risedronate Sodium + Chemotherapy | Drug | Camrelizumab: 200 mg, intravenous drip, administered in line with the chemotherapy regimen cycles. Risedronate Sodium: Oral administration. Should be taken while in an upright position at least 30 minutes before the first food or drink of the day, swallowed with a full glass of plain water (approximately 200 ml). Patients should not lie down for at least 30 minutes after taking. Dosage is one 5 mg tablet once daily. Chemotherapy regimens are selected by the physician and include, but are not limited to: TAC, TP-AC, AC-T, etc. A total of 6 treatment cycles are planned; the subsequent regimen will be chosen by the investigator. |
| Measure | Description | Time Frame |
|---|---|---|
| ORR | Objective Response Rate | At the end of every 2 Cycles (each cycle is 21 days), From first treatment Cycle until achieving complete response (CR) or response (PR) per RECIST v1.1, assessed up to 1 year, defined as the proportion of patients achieving complete response |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of adverse events of any grade | Incidence of adverse events (AEs) and serious adverse events (SAEs) of any grade, assessed according to NCI-CTCAE version 6.0 criteria. | Safety follow-up will be conducted from the first dose until the end of treatment. Adverse events occurring during this period will be recorded, with a maximum assessment period of 2 years. |
| Measure | Description | Time Frame |
|---|---|---|
| Mechanism Exploration | The mechanism of Camrelizumab combined with Risedronate Sodium and chemotherapy | The mechanism of Camrelizumab combined with Risedronate Sodium and chemotherapy, with a maximum follow-up of up to 2 years. |
Inclusion Criteria:
(1) Hematology requirements: ANC ≥ 1.5 × 10⁹/L; PLT ≥ 90 × 10⁹/L; Hb ≥ 90 g/L. (2) Biochemistry requirements: TBIL ≤ 1.5 × upper limit of normal (ULN); ALT and AST ≤ 1.5 × ULN; Alkaline phosphatase ≤ 2.5 × ULN; BUN and Cr ≤ 1.5 × ULN and creatinine clearance ≥ 50 mL/min (by Cockcroft-Gault formula).
(3) Thyroid-stimulating hormone (TSH) ≤ ULN (if abnormal, T3 and T4 levels should be checked; patients with normal T3 and T4 levels can be enrolled).
(4) Cardiac color Doppler ultrasound and echocardiography: Left ventricular ejection fraction (LVEF) ≥ 50%.
(5) 18-lead ECG: Fridericia-corrected QT interval (QTcF) < 480 ms for females.
7.Women of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days before enrollment and voluntarily agree to use adequate contraception during the observation period and for 4 months after the last dose of the study drug.
8.Voluntary participation, signed informed consent, and good compliance.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Harbin Medical University Cancer Hospital | Harbin | Heilongjiang | 158100 | China |
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|
| OS | Overall Survival | Refers to the time from randomization to death due to any cause, with a maximum assessment period of 2 years. |
| 6-PFS Rate | 6-Month Progression-Free Survival Rate | The proportion of patients who have not experienced tumor progression or death from any cause by 6 months from the start of first treatment, with a maximum assessment period of 6 months. |
| DOR | Duration of Response | Refers to the time from the first assessment of CR or PR to the first assessment of disease progression (PD) or death from any cause. The assessment period is up to 2 years. |
| DCR | Disease Control Rate: Refers to the percentage of patients with evaluable cases who achieve Complete Response (CR), Partial Response (PR), or Stable Disease (SD) following treatment. | Patients undergo imaging evaluation in every 2 cycles(each cycyle is 21 days)until achieving SD per RECIST v1.1 or through study completion, assessed up to 1 year. |
| Incidence of new bone metastases | Refers to the ratio of the number of new cases with bone metastases to the total number of cases in the same population during the corresponding period. | Starting from the first dose, regular imaging follow-ups will be conducted to monitor for the occurrence of bone metastases, continuing until 2 years. |
| BMD | Bone Mineral Density | A key indicator for measuring bone strength, reflecting the mineral content (mainly calcium, phosphorus, etc.) per unit volume or unit area of bone. Assessments will be conducted once every three months for up to 2 year. |
| ID | Term |
|---|---|
| D064726 | Triple Negative Breast Neoplasms |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C000631724 | camrelizumab |
| D000068296 | Risedronic Acid |
| D004358 | Drug Therapy |
| ID | Term |
|---|---|
| D004164 | Diphosphonates |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013812 | Therapeutics |
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