Study of Radiotherapy Combined With Platinum, Adebrelimab and Bevazumab in the Treatment of TNBC-BM.

Official title

A Prospective, Single-arm, Multi-centre, Phase II Clinical Study of Radiotherapy Combined With Platinum, Adebrelimab and Bevazumab in the Treatment of Patients With Brain Metastasis of Triple Negativebreast Cancer

Overview

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.

Interventions

• Drug Radiotherapy followed by systemic therapy
  Radiotherapy followed by Adebrelimab+Bevacizumab+Cisplatin/Carboplatin
• Drug Systemic therapy followed by radiotherapy
  Adebrelimab+Bevacizumab+Cisplatin/Carboplatin followed by radiotherapy.

Primary outcome measures

• 12-month CNS-PFS rate [Time frame: From treatment initiation to 12 months.]

Secondary outcome measures (12)

• CNS ORR [Time frame: From treatment initiation until CNS progression, assessed up to 36 months.]
• CNS CBR [Time frame: From treatment initiation until CNS progression, assessed up to 36 months.]
• ORR [Time frame: From treatment initiation until disease progression, assessed up to 36 months.]
• CBR [Time frame: From treatment initiation until disease progression, assessed up to 36 months.]
• DoR [Time frame: 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 [Time frame: From treatment initiation until CNS progression or death from any cause, whichever occurs first, assessed up to 36 months.]
• PFS [Time frame: From treatment initiation until disease progression or death from any cause, whichever occurs first, assessed up to 36months.]
• OS [Time frame: From treatment initiation until death from any cause, assessed up to 36 months.]
• AE [Time frame: From first dose through 30 days after the last dose of study treatment, assessed up to 36 months.]
• Neurocognitive function assessment 1 [Time frame: 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 [Time frame: 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 [Time frame: 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.]

Eligibility criteria

Inclusion criteria

• Age ≥18 years and ≤70 years, gender not limited;
• ECOG score 0-2;
• 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;
• 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;
• Expected survival ≥8 weeks;
• 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.
• Confirm progression after radiotherapy;
• Provide sufficient fresh tissue specimens or tumor samples (primary lesion and/or metastatic lesions) ≥10 smears before treatment (preferably brain metastatic lesion specimens) for biomarker analysis.
• Use mannitol, hormones, or anticonvulsants before the first dose, but the drug treatment dose must be stable for at least one week without needing to be increased.Neurological symptoms stable for ≥1 week are required for enrollment.
• 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

• Leptomeningeal metastases or cystic metastases confirmed by MRI or lumbar puncture;
• Presence of third-space effusion (e.g., massive pleural effusion and ascites) that cannot be controlled by drainage or other methods;
• 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;
• 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;
• Participation in other drug clinical trials within 2 weeks prior to enrollment;
• Concurrent anti-tumor treatment for any other tumor;
• 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;
• 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;
• A known history of allergy to any component of the medications in this regimen;
• 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;
• A history of a defined neurological or psychiatric disorder, including epilepsy or dementia;
• 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;
• 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.);
• Any other circumstances deemed unsuitable for participation in this study by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Fudan University Shanghai Cancer Center — Shanghai

Identifiers

NCT: NCT07638852 · 2510331-6

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗