TNBC, Triple Negative Breast Cancer, Brain Metastasases
Conditions
Keywords
TNBC, brain metastatic, radiotherapy, Bevacizumab, adebrelimab
Brief summary
This is an open-label, prospective, two-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.
Interventions
RADIATIONRadiation Therapy
Patients will receive either Fractionated Stereotactic Radiotherapy (FSRT) or Whole Brain Radiotherapy (WBRT), at the discretion of the treating physician based on the number, size, and location of brain metastases.
DRUGAdebelimab
20mg/kg, IV, D1, Q3W
DRUGBevacizumab
7.5mg/kg, IV, D1, Q3W
Cisplatin 75mg/m2, IV, D1, Q3W; or carboplatin: AUC=5, IV, D1, Q3W
Sponsors
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years and ≤70 years, gender not limited; 2. ECOG score 0-2; 3. Pathologically confirmed HR-negative/HER2-negative breast cancer patients with evidence of local recurrence or metastasis, unsuitable for curative surgical resection or radiotherapy; HR-negative is defined as ER-negative and PR-negative, with positive tumor cells accounting for \<10% of all tumor cells; 4. Must not have previously used platinum-based drugs, or must have previously used platinum-based drugs (cisplatin or carboplatin and only one regimen) and meet the following definition of platinum sensitivity: no progression during at least 4 cycles of platinum-based therapy, and subsequent disease progression occurring more than 3 months after the last platinum-based therapy; 5. Expected survival ≥8 weeks; 6. MRI confirms brain metastasis, with at least one previously untreated intracranial brain parenchymal metastatic lesion with a longest diameter ≥1.0 cm;If the brain metastatic lesion has previously undergone radiotherapy, MRI is required to confirm progression after radiotherapy. 7. Provide sufficient fresh tissue specimens or tumor samples (primary lesion and/or metastatic lesions) ≥10 slides before treatment (preferably brain metastatic lesion specimens) for biomarker analysis. 9\. Patients receiving mannitol, corticosteroids, or anticonvulsants prior to the first dose are eligible for enrollment if the doses of these concomitant medications have been stable for at least 1 week without escalation, and neurological symptoms have remained stable for ≥1 week. 10\. Organ function levels must meet the following requirements: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
1. Leptomeningeal metastases or cystic metastases confirmed by MRI or lumbar puncture; 2. Presence of third-space effusion (e.g., massive pleural effusion and ascites) that cannot be controlled by drainage or other methods; 3. Received whole-brain radiotherapy, chemotherapy, or surgery within 2 weeks prior to treatment with the investigational drug, or received endocrine therapy within one week prior to treatment; 4. Previous use of bevacizumab and PD-1/PD-L1 inhibitors, excluding the following: no disease progression during bevacizumab and PD-1/PD-L1 inhibitor use, investigators believe no drug resistance has been confirmed, and continued use would benefit the subject; short-term bevacizumab use to relieve cerebral edema; 5. Participation in other drug clinical trials within 2 weeks prior to enrollment; 6. Concurrent anti-tumor treatment for any other tumor; 7. History of other malignancies within the past 5 years, excluding cured cervical carcinoma in situ, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin; 8. History of any heart disease, including: (1) arrhythmia requiring medication or of clinical significance; (2) myocardial infarction; (3) heart failure; (4) any other heart disease deemed unsuitable for participation in this trial by the investigator; 9. A known history of allergy to any component of the medications in this regimen; 10. A history of immunodeficiency, including a positive HIV test, active hepatitis B/C, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; 11. A history of a defined neurological or psychiatric disorder, including epilepsy or dementia; 12. Pregnant or lactating women, women of childbearing age with a positive baseline pregnancy test, or patients who do not wish to use effective contraception throughout the trial; 13. In the investigator's judgment, a serious comorbidity that would jeopardize patient safety or affect the patient's ability to complete the study (including but not limited to severe hypertension uncontrolled by medication, severe diabetes, active infection, thyroid disease, etc.); 14. Any other circumstances deemed unsuitable for participation in this study by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 12-month CNS-PFS rate | From randomization up to 12 months. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CNS ORR | Up to 24 months(Efficacy assessments at 6 weeks post-treatment initiation, followed by every 9 weeks thereafter starting from Month 12) | ntracranial objective response rate is defined as the proportion of patients who achieve a best overall intracranial response of complete response (CR) or partial response (PR), as assessed by RANO-BM criteria. |
| CNS CBR | Up to 24 months (Efficacy assessments at 6 weeks post-treatment initiation, followed by every 9 weeks thereafter starting from Month 12) | Clinical benefit rate is defined as the proportion of patients who achieve a best overall intracranial response of complete response (CR), partial response (PR), or stable disease (SD) lasting for at least 24 weeks, as assessed by RANO-BM criteria. |
| ORR | Up to 24 months (Efficacy assessments at 6 weeks post-treatment initiation, followed by every 9 weeks thereafter starting from Month 12) | Objective response rate is defined as the proportion of patients who achieve a best overall response of complete response (CR) or partial response (PR) |
| CBR | Up to 24 months (Efficacy assessments at 6 weeks post-treatment initiation, followed by every 9 weeks thereafter starting from Month 12) | clinical benefit rate is defined as the proportion of patients who achieve a best overall response of complete response (CR), partial response (PR), or stable disease (SD) lasting for at least 24 weeks. |
| DoR | From first documented response to progression or death, assessed up to 24 months | Duration of response is defined as the time from first documented objective response (CR or PR) until disease progression or death from any cause, whichever occurs first. |
| CNS PFS | From randomization to intracranial progression or death, assessed up to 24 months. | Intracranial progression-free survival is defined as the time from treatment initiation until intracranial disease progression per RANO-BM criteria or death from any cause, whichever occurs first. |
| PFS | From randomization to progression or death, assessed up to 24 months. | Progression-free survival is defined as the time from treatment initiation to disease progression or death from any cause, whichever occurs first. |
| OS | From randomization to death, assessed up to 24 months. | Overall survival is defined as the time from the start of treatment to death from any cause. |
| Adverse Events (AE) | From randomization through 30 days after the last dose of study treatment, assessed up to 24 months. | Adverse events will be assessed and graded according to NCI-CTCAE version 5.0. |
| Hopkins Verbal Learning Test-Revised (HVLT-R) | At screening, 12, 24, 36, 48 weeks, 1.5 years, and 2 years after radiotherapy completion | Neurocognitive function assessed using the Hopkins Verbal Learning Test-Revised (HVLT-R). |
| Functional Assessment of Cancer Therapy-Brain (FACT-Br) | At screening, within 3 days before each cycle of treatment, and at end of treatment or safety follow-up, assessed up to 24 months | Quality of life assessed using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire. |
| Mini-Mental State Examination (MMSE) | At screening, 12, 24, 36, 48 weeks, 1.5 years, and 2 years after radiotherapy completion | Neurocognitive function assessed using the Animal Verbal Fluency Test. |
| Animal Verbal Fluency 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. | Animal Oral Vocabulary Association Test |
| Trail Making Test (TMT-A/TMT-B) | At screening, 12, 24, 36, 48 weeks, 1.5 years, and 2 years after radiotherapy completion | Neurocognitive function assessed using the Trail Making Test (TMT-A/TMT-B) |
| EORTC QLQ-C30 | At screening, within 3 days before each cycle of treatment, and at end of treatment or safety follow-up, assessed up to 24 months | Quality of life assessed using the EORTC Core Quality of Life Questionnaire (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. |
| EORTC QLQ-BN20 | At screening, within 3 days before each cycle of treatment, and at end of treatment or safety follow-up, assessed up to 24 months | Quality of life assessed using the EORTC Quality of Life Questionnaire for Brain Neoplasms (QLQ-BN20). This 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. |
Countries
China
Outcome results
None listed