Neoadjuvant Trastuzumab, Pertuzumab Plus Metronomic Vinorelbine for Elderly HER2-Positive Breast Cancer
A Multicenter, Prospective Clinical Study of Neoadjuvant Therapy With Trastuzumab Plus Pertuzumab Combined With Metronomic Vinorelbine Chemotherapy in Elderly Patients With Early-Stage HER2-Positive Breast Cancer
English Translation (Professional Medical Version) This study is a multicenter, prospective clinical trial designed to investigate the efficacy and safety of neoadjuvant therapy with trastuzumab plus pertuzumab combined with metronomic vinorelbine chemotherapy in elderly patients with HER2-positive breast cancer.
Eligible patients were aged ≥70 years, with histopathologically confirmed primary HER2-positive breast cancer, and met the indications for neoadjuvant therapy as stipulated in the clinical guidelines for the diagnosis and treatment of breast cancer.
A Simon two-stage design was employed in this study, with a planned total enrollment of 45 patients. In the first stage, 14 patients would be enrolled. If the number of observed responders was no more than 6, the trial would be terminated; otherwise, the trial would advance to the second stage, and the total sample size would be expanded to 45 patients.
The treatment regimen comprised 6 cycles of trastuzumab combined with pertuzumab (subcutaneous pertuzumab/trastuzumab fixed-dose combination was permitted as an alternative to intravenous formulations) plus metronomic vinorelbine therapy. Tumor response was assessed by imaging every 2 cycles. Patients with a confirmed response would complete all 6 cycles of treatment and undergo surgery per investigator assessment; postoperative pathological reports would be evaluated to determine the achievement of tpCR. For non-responders, the treatment regimen would be modified or surgery would be performed at the investigator's discretion.
調査の概要
状態
研究の種類
入学 (推定)
段階
- 適用できない
参加基準
適格基準
就学可能な年齢
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Subjects voluntarily participate in this study and sign informed consent.
- Age ≥70 years at the time of informed consent signing.
- ECOG performance status (PS) 0-1; expected survival >3 months.
- Primary HER2-positive breast cancer confirmed by histopathology or cytology.
- Primary tumor diameter >2 cm, or axillary lymph node metastasis.
- Laboratory indicators conform to the following standards:
Absolute neutrophil count (ANC) ≥1.5×10⁹/L; Absolute lymphocyte count (LC) ≥0.5×10⁹/L; Platelet count (PLT) ≥100×10⁹/L; Hemoglobin (Hb) ≥90 g/L; White blood cell count (WBC) 3.0×10⁹/L ≤ WBC ≤15×10⁹/L. Serum biochemistry (no blood transfusion or albumin infusion within 7 days before screening): ALT and AST ≤2.5×ULN; ALT and AST ≤5×ULN in patients with hepatic metastases. ALP ≤2.5×ULN (≤5×ULN for patients with bone tumor metastasis). BUN and Cr ≤1.5×ULN, and creatinine clearance ≥60 mL/min (Cockcroft-Gault formula).
PT and APTT ≤1.5×ULN, INR ≤1.5×ULN (patients not receiving anticoagulation therapy).
Urine protein <2+. If urine protein ≥2+, 24-hour urinary protein quantification ≤1 g.
Thyroid-stimulating hormone (TSH) ≤ULN. Left ventricular ejection fraction (LVEF) ≥50%. Patients with abnormal TSH may be enrolled as long as T3 and T4 levels are normal.
Exclusion Criteria:
- Stage Ⅳ metastatic breast cancer, or patients who cannot undergo curative surgical resection after neoadjuvant therapy as assessed by investigators.
- Prior anti-tumor therapies including chemotherapy, endocrine therapy, anti-HER2 biological therapy, or previous breast surgery (excluding diagnostic biopsy for primary breast cancer).
- Other malignancies diagnosed within 3 years or concurrent malignant tumors at enrollment.
- The following cases are eligible: Other malignancies treated solely by surgery with continuous 5-year disease-free survival (DFS); cured cervical carcinoma in situ, non-melanoma skin cancer, superficial bladder tumors (Ta: non-invasive tumor, Tis: carcinoma in situ, T1: basement membrane-invasive tumor).
- Major surgery, incisional biopsy or severe traumatic injury within 28 days before study treatment (excluding diagnostic biopsy of primary breast cancer).
- Persistent unhealed wounds or fractures.
- History of uncontrolled psychoactive drug abuse or psychiatric disorders.
Severe and/or uncontrolled underlying systemic diseases, including:
- History of hypertensive crisis or hypertensive encephalopathy; uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg after antihypertensive treatment).
- Confirmed heart failure or cardiac systolic dysfunction (LVEF <55%).
- Grade ≥2 myocardial ischemia, myocardial infarction, arrhythmia (QTc ≥450 ms for males, QTc ≥470 ms for females), or grade ≥2 congestive heart failure (NYHA classification).
Angina pectoris requiring anti-anginal medication.
- Comorbidities interfering with scheduled treatment, including severe pulmonary dysfunction, active pulmonary disease, or uncontrolled severe infection (≥Grade 2 per CTCAE 5.0).
- Allergy to any investigational drug, active ingredients or pharmaceutical excipients.
- Subjects with comorbidities that threaten safety or affect study completion, or those unsuitable for enrollment according to investigator judgment.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：NHP
Vinorelbine soft capsules 40 mg, orally (PO), three times weekly (tiw) Trastuzumab: initial loading dose 8 mg/kg, maintenance dose 6 mg/kg, intravenous infusion, administered once every 3 weeks. Pertuzumab: initial loading dose 840 mg, maintenance dose 420 mg, intravenous infusion, administered once every 3 weeks. Each treatment cycle lasts 3 weeks. Imaging evaluations, including breast MRI, ultrasonography and computed tomography (CT), were performed every 2 cycles. For patients with tumor response, surgical indication was assessed after 6 cycles of treatment. Postoperative pathology was used to determine the pathological complete response (pCR) rate, and adjuvant treatment regimens were formulated according to postoperative pathological findings. |
Vinorelbine soft capsules 40 mg, orally (PO), three times weekly (tiw) Trastuzumab: initial loading dose 8 mg/kg, maintenance dose 6 mg/kg, intravenous infusion, administered once every 3 weeks. Pertuzumab: initial loading dose 840 mg, maintenance dose 420 mg, intravenous infusion, administered once every 3 weeks. Each treatment cycle lasts 3 weeks. Imaging evaluations, including breast MRI, ultrasonography and computed tomography (CT), were performed every 2 cycles. For patients with tumor response, surgical indication was assessed after 6 cycles of treatment. Postoperative pathology was used to determine the pathological complete response (pCR) rate, and adjuvant treatment regimens were formulated according to postoperative pathological findings. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Total pathological complete response (tpCR)
時間枠：through study completion, an average of 1 year
|
It indicates that no residual invasive cancer cells are detected pathologically in both primary breast lesions and axillary lymph nodes after neoadjuvant therapy and surgical operation.
|
through study completion, an average of 1 year
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Event-free survival （EFS）
時間枠：5 years
|
The time interval from study enrollment to the occurrence of any prognosis-impacting events, including local or distant recurrence, secondary primary malignancy, and all-cause death.
|
5 years
|
|
Objective response rate in patients undergoing neoadjuvant therapy （ORR）
時間枠：through study completion, an average of 1 year
|
The proportion of patients who achieve remarkable tumor shrinkage meeting the criteria of partial response or complete response.
|
through study completion, an average of 1 year
|
|
Disease control rate（DCR）
時間枠：through study completion, an average of 1 year
|
The proportion of patients with clinically controlled tumors, including those with complete response, partial response and stable disease.
|
through study completion, an average of 1 year
|
|
Invasive disease-free survival （iDFS）
時間枠：5 years
|
The time from surgery to invasive breast cancer recurrence, non-breast second primary tumor, or death from any cause.
|
5 years
|
|
Relapse-free survival （RFS）
時間枠：5 years
|
The time from surgery to any local or distant breast cancer recurrence, excluding non-breast second primary tumors and breast cancer-unrelated mortality.
|
5 years
|
|
Distant metastasis-free survival （DMFS）
時間枠：5 years
|
The time from treatment initiation to the development of distant metastasis.
|
5 years
|
|
Overall survival （OS）
時間枠：7 years
|
The time from subject enrollment to all-cause death.
|
7 years
|
|
Safety evaluation （SE）
時間枠：through study completion, an average of 1 year
|
The proportion of patients with grade 3 or higher adverse events
|
through study completion, an average of 1 year
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- NHP-ELDER-BC
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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