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This is an open-label, prospective, single-arm, multicenter phase II clinical trial. The aim is to explore the efficacy and safety of radiotherapy combined with cisplatin/carboplatin, adebrelimab, and bevacizumab in patients with triple-negative breast cancer and brain metastases.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Radiotherapy followed by systemic therapy group | Experimental | Patient who are eligible for inclusion will recieve radiotherapy first, followed by adebrelimab, bevacizumab and Cisplatin/Carplatin. |
|
| Systemic therapy followed by radiotherapy group | Experimental | Patient who are eligible for inclusion will recieve adebrelimab, bevacizumab and Cisplatin/Carplatin followed by radiotherapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Radiotherapy followed by systemic therapy | Drug | Radiotherapy followed by Adebrelimab+Bevacizumab+Cisplatin/Carboplatin |
|
| Measure | Description | Time Frame |
|---|---|---|
| 12-month CNS-PFS rate | The 12-month CNS-PFS rate was used for intracranial efficacy assessment based on RANO-BM, and extracranial efficacy assessment based on RECIST 1.1. | From treatment initiation to 12 months. |
| Measure | Description | Time Frame |
|---|---|---|
| CNS ORR | Intracranial objective response rate: Time elapsed from the start of treatment until the Intracranial tumor achieves objective response (PR or CR) | From treatment initiation until CNS progression, assessed up to 36 months. |
| CNS CBR |
| Measure | Description | Time Frame |
|---|---|---|
| cytological and multi-omics testing | Collect and preserve tumor samples (primary lesions and/or metastases, preferably brain metastases) ≥10 blotting sheets or fresh tissue specimens; collect 8 ml of procoagulant, 8 ml of anticoagulant, and 5 ml of cerebrospinal fluid from subjects at baseline, after C2, and at disease progression or upon exit from the study for cytological and multi-omics testing, exploratoryly investigating factors that may influence or predict the efficacy of radiotherapy combined with systemic therapy. |
Inclusion Criteria:
1) Complete blood count:
ANC ≥1.5×10⁹/L;
PLT ≥75×10⁹/L;
Hb ≥90 g/L (blood transfusion or drug treatment is allowed to ensure hemoglobin levels); 2) Coagulation function: INR ≤1.5, APTT ≤1.5×ULN; PT not exceeding the upper limit of normal.
3) Blood Biochemistry
TBIL ≤ 1.5 × ULN;
ALT and AST ≤ 3 × ULN (liver metastases ≤ 5.0 × ULN);
Cr ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula); 3) Echocardiography: LVEF ≥ 50%; 4) 12-lead ECG: Fridricia-corrected QT interval (QTcF) < 470 ms for women and < 450 ms for men; 10. Voluntary participation in this study, signing informed consent, good adherence, and willingness to cooperate with follow-up.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fudan University Shanghai Cancer Center | Recruiting | Shanghai | Shanghai Municipality | 200032 | China |
Individual participant data will not be shared. The informed consent states that participants' records will be kept in a locked filing cabinet and accessed only by the research team, with access granted to regulatory authorities or the ethics committee solely for on-site monitoring purposes. The consent does not include provision for sharing de-identified individual participant data with other researchers or depositing data in public repositories.
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| Systemic therapy followed by radiotherapy | Drug | Adebrelimab+Bevacizumab+Cisplatin/Carboplatin followed by radiotherapy. |
|
This refers to the proportion of patients who achieve complete remission, partial remission, or stable disease for a certain period of time after receiving treatment: CR+ PR+ SD ≧ 24 weeks
| From treatment initiation until CNS progression, assessed up to 36 months. |
| ORR | The proportion of patients who achieved partial response (PR) and complete remission (CR) after receiving a certain anti-tumor treatment, resulting in tumor shrinkage. | From treatment initiation until disease progression, assessed up to 36 months. |
| CBR | The proportion of patients who achieve complete remission, partial remission, or stable disease for a certain period of time after receiving treatment: CR+ PR+ SD ≧ 24 weeks | From treatment initiation until disease progression, assessed up to 36 months. |
| DoR | Time from first remission to disease progression | From the date of first documented response until disease progression or death from any cause, whichever occurs first, assessed up to 36 months. |
| CNS PFS | Intracranial progression-free survival: Time from the start of treatment to the patient's "progression of intracranial disease" or "death from any cause" | From treatment initiation until CNS progression or death from any cause, whichever occurs first, assessed up to 36 months. |
| PFS | The time from the start of treatment to the first observed disease progression or death from any cause. | From treatment initiation until disease progression or death from any cause, whichever occurs first, assessed up to 36months. |
| OS | Time from the start of treatment to death from any cause | From treatment initiation until death from any cause, assessed up to 36 months. |
| AE | AE, according to NCI-CTC AE 5.0 | From first dose through 30 days after the last dose of study treatment, assessed up to 36 months. |
| Neurocognitive function assessment 1 | Hopkins Oral Learning Test (HVLT) | From enrollment to the end of treatment at 24 months,evaluations were conducted at screening, 12 weeks, 24 weeks, 36 weeks, 48 weeks, 1.5 years, and 2 years after completion of radiotherapy. |
| Quality of life assessment 1 | Functional Assessment of Cancer Therapy - Brain (FACT-Br) | Screening, within 3 days before each treatment administration, at the end of treatment, and during safety follow-up, assessed up to 36 months. |
| Neurocognitive function assessment 2 | Mini-mental Test (MMSE) | From enrollment to the end of treatment at 24 months,evaluations were conducted at screening, 12 weeks, 24 weeks, 36 weeks, 48 weeks, 1.5 years, and 2 years after completion of radiotherapy. |
| Neurocognitive function assessment 3 | Animal Oral Vocabulary Association Test | From enrollment to the end of treatment at 24 months,evaluations were conducted at screening, 12 weeks, 24 weeks, 36 weeks, 48 weeks, 1.5 years, and 2 years after completion of radiotherapy. |
| Neurocognitive function assessment 4 | Connect-the-Dots Test (TMT-A/TMT-B) | From enrollment to the end of treatment at 24 months,evaluations were conducted at screening, 12 weeks, 24 weeks, 36 weeks, 48 weeks, 1.5 years, and 2 years after completion of radiotherapy. |
| Quality of life assessment 2 | The EORTC QLG Core Questionnaire (EORTC QLQ-C30), scoring from 0 to 100. This questionnaire is for functional and global quality of life scales, higher scores mean a better level of functioning. For symptom-oriented scales, a higher score means more severesymptoms. | Screening, within 3 days before each treatment administration, at the end of treatment, and during safety follow-up, assessed up to 36 months. |
| Quality of life assessment 3 | The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Brain Neoplasm (QLQ-BN20) aims to evaluate the effects of the tumour and its treatment on symptoms, functions and health-related quality of life (HRQoL) of brain tumour patients. The scale scoring form 0 to 100, and a higher score generally indicates more severe symptoms and poorer quality of life. | Screening, within 3 days before each treatment administration, at the end of treatment, and during safety follow-up, assessed up to 36 months. |
| These tests will be conducted at baseline, at the end of Cycle 2 (each cycle is 21 days), and at disease progression or when leaving the study, assessed up to 36 months. |
| 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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