Olaparib+Trastuzumab+Pertuzumab Neoadjuvant for Elderly HER2+ Breast Cancer

Official title

A Study on the Efficacy and Safety of Olaparib Combined With Trasotuzumab and Pertuzumab in Neoadjuvant Treatment for Elderly Patients With HER-2 Positive Breast Cancer

Overview

This is a single-center, interventional, prospective clinical study. A total of 45 patients aged ≥ 60 years with ECOG PS 0-1 who have histologically confirmed, treatment-naïve, unilateral primary invasive HER-2-positive breast cancer will be enrolled according to predefined inclusion/exclusion criteria. Participants will receive olaparib 300 mg orally twice daily combined with investigator-selected HP regimen (trastuzumab 8 mg/kg C1 → 6 mg/kg C2-6 and pertuzumab 840 mg C1 → 420 mg C2-6, both q3w) for up to six neoadjuvant cycles. Tumor response will be assessed after cycle 2; patients with inadequate response may switch to an alternative neoadjuvant regimen devised by the investigator for an additional 2-4 cycles before surgery, whereas responding patients will continue the original regimen to complete six cycles prior to surgery. Post-operatively, adjuvant therapy will be determined by pathological results: patients achieving pCR will complete one year of HP, while those with residual disease may receive escalated investigator-determined treatment. The primary endpoint is bpCR; secondary endpoints include 2-cycle ORR, tpCR, iDFS, incidence of adverse events, and quality-of-life assessments. Treatment will continue until disease progression or unacceptable toxicity. The study aims to evaluate the efficacy and safety of olaparib plus trastuzumab and pertuzumab as neoadjuvant therapy for elderly HER-2-positive breast cancer patients.

Interventions

• Drug olaparib combined with trastuzumab and pertuzumab
  Orelaparib (300 mg bid) combined with the investigator-selected HP regimen (trastuzumab 8 mg/kg C1→6 mg/kg C2-6, patuzumab 840 mg C1→420 mg C2-6, q3w) for neoadjuvant therapy for up to 6 cycles

Primary outcome measures

• Pathological complete remission rate in breast cancer [Time frame: After 6 cycles of treatment with olaparib combined with trastuzumab and pertuzumab, the rate of complete pathological response of the breast was evaluated.]

Eligibility criteria

Inclusion criteria

• (1) Age ≥ 60 years old, female; (2) Patients with newly diagnosed unilateral primary invasive breast cancer confirmed by histopathological examination; (3) HER-2 positive (defined as immunohistochemical result of 3+ or immunohistochemical result of 2+ and in situ hybridization result positive); (4) Patients with TNM stage of II - IIIA (cT2N0M0, cT1N1M0, cT2N1M0, cT3N0M0, cT1N2M0, cT2N2M0, cT3N1M0, cT3N2M0); (5) According to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, having at least one evaluable target lesion; (6) ECOG performance status score of 0 - 1; (7) Having adequate organ function, which meets the following criteria:

• Blood routine examination: (within 7 days without using hematopoietic growth factors and blood transfusion)

• White blood cells ≥ 3.0×109/L, neutrophils ≥ 1.5×109/L;
• Platelets ≥ 100×109/L;
• Hemoglobin ≥ 90g/L;

② Biochemical examination:

• Total bilirubin ≤ 1.5×ULN;
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.0×ULN;
• Serum creatinine ≤ 1.5×ULN or creatinine clearance rate ≥ 50 mL/min (calculated according to the Cockcroft-Gault formula);

③ Cardiac function examination:

• Left ventricular ejection fraction (LVEF) ≥ 50%; (8) Voluntarily joining this study, signing informed consent, having good compliance and willing to cooperate with follow-up.

Exclusion criteria

• (1) Concealed breast cancer, inflammatory breast cancer and eczematous carcinoma; (2) Patients known to be allergic to the active ingredients or other components of the study drug; (3) Those with severe heart diseases or discomfort, and expected to be unable to tolerate chemotherapy, including but not limited to: ① Fatal arrhythmia or higher-level atrioventricular block (second-degree type 2 atrioventricular block or third-degree atrioventricular block). ② Unstable angina pectoris. ③ Clinically significant valvular heart disease. ④ Echocardiogram showing transmural myocardial infarction; (4) Severe or uncontrolled infections that may affect the study treatment or the evaluation of study results, including but not limited to active hepatitis virus infection, positive human immunodeficiency virus (HIV) antibody, pulmonary infection, etc.; (5) History of other malignant tumors within the past 5 years (excluding cured cervical carcinoma in situ or skin basal cell carcinoma, etc.); (6) Participated in other clinical trials within 4 weeks before the study; (7) The investigator believes that the patient has any other conditions that are not suitable for participating in the study.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Zhejiang Cancer Hospital — Hangzhou

Identifiers

NCT: NCT07695259 · IRB-2025-873（IIT）

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗