2024-514458-61-01招募中2 期
NeoAdjuvant Dynamic marker - Adjusted Personalized Therapy comparing trastuzumab-deruxtecan versus pacli-/docetaxel+carboplatin+trastuzumab+pertuzumab in HER2+ early breast cancer (ADAPT-HER2-IV)
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 402
- 试验地点
- 45
- 主要终点
- pCR rate after neoadjuvant treatment, defined as ypTis/ypN0, to be compared between all T-DXd treated patients versus standard-of- care (PAC+T+P or PAC/DOC+Carbo+T+P) (pooled across cohorts) Hypotheses: H0: pCR T-DXd = pCR standard-of-care H1: pCR T-DXd ≠ pCR standard-of-care
研究概览
简要总结
- The first co-primary objective of the study is the comparison of the pathologic complete response (pCR) rates after 12 or 18 weeks of neoadjuvant treatment with T-DXd versus standard-of-care (PAC+T+P or PAC/DOC+Carbo+T+P) in pooled risk cohorts
- The second co-primary objective is to evaluate whether 3-year distant- disease-free survival equals or exceeds 92% in T-DXd treated patients from both risk cohorts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 主要目的
- Follow-up Phase
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Female patients with invasive, untreated HER2+ breast cancer (as assessed by local pathology) maximum 6 weeks before registration (standard-of-care diagnostic biopsy according to current AGO guidelines)
- •Female subjects must not donate, or retrieve for their own use, ova from the time of randomisation and throughout the study treatment period, and for at least 7 months after the final study drug administration. (refer to protocol for detailed information)
- •Age ≥18 years
- •a) Cohort 1: low- to intermediate-risk for recurrence as per investigator´s decision (recommendation: cT1c – cT2 (1 - ≤3cm) and cN0; cT1a/b, cN0 is excluded!), OR b) Cohort 2: intermediate- to high-risk for recurrence as per investigator´s decision (recommendation: cT2 (>3 - ≤5cm), cN0) c) Elderly patients (≥ 65 years) may be assigned to any cohort as per investigator’s decision
- •Written informed consent
- •LVEF ≥ 50% within 28 days before randomisation
- •Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1
- •Adequate bone marrow and organ function within 14 days before randomisation as defined by the following laboratory values: • absolute neutrophil count ≥ 1.5 × 109/L, • platelets ≥ 100 × 109/L, • hemoglobin ≥ 9.0 g/dL: • estimated glomerular filtration rate (eGFR) ≥ 30 mL/min by a Cockcroft-Gault formula, • INR ≤ 1.5, • serum creatinine < 1.5 mg/dL, • total bilirubin < 1.5 ULN, except for patients with Gilbert’s Syndrome who may only be included if the total bilirubin is ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN, • aspartate transaminase (AST) < 2.5 × ULN, • alanine transaminase (ALT) < 2.5 × ULN.
- •Adequate treatment washout period before randomisation (refer to protocol for detailed information)
- •Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential (refer to protocol for detailed information). Post-menopausal status is accepted for women, who at the time of initiation of study medication, either • had underwent bilateral oophorectomy, or • are ≥ 60 years of age, or • are < 60 years of age and amenorrhoeic for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) • and/or whose FSH- and estradiol-blood values are within the postmenopausal range per local laboratory normal range.
排除标准
- •Non-operable breast cancer including inflammatory breast cancer
- •Woman of child-bearing potential defined as a woman physiologically capable of becoming pregnant, and not using highly effective methods of contraception during the study treatment and for 7 months after stopping the treatment.
- •Use of oral (oestrogen and progesterone), transdermal, injected, or implanted hormonal methods of contraception as well as hormonal replacement therapy.
- •Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject’s participation in the clinical study or evaluation of the clinical study results.
- •Patients with a medical history of myocardial infarction (MI) within 6 months before randomisation, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV), Subjects with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before enrolment to rule out MI.
- •Corrected QT interval (QTcF) prolongation to > 470 msec (females) based on average of the screening triplicate12-lead ECG.
- •History of (non-infectious) ILD / pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- •Lung criteria: o Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder o Any autoimmune, connective tissue or inflammatory disorders (e.g., Rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of randomisation. o Prior pneumonectomy (complete) Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
- •Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Patients should be tested for HIV prior to randomisation if required by local regulations or ethics committee (EC).
- •Receipt of live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of trastuzumab deruxtecan or carboplatin. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IMP.
- •Known allergy or hypersensitivity to study treatment (T-DXd), to comparator (SoC-) treatment, or any of the study drug / comparator (SoC-) excipients.
- •cT1a/b, cN0 breast cancer
- •History of severe hypersensitivity reactions to other monoclonal antibodies.
- •Pregnant or breastfeeding female patients, or patients who are planning to become pregnant.
- •Any previous history of invasive breast cancer
- •Primary malignancies within 5 years, with the exception of • adequately resected non-melanoma skin cancer • curatively treated in-situ disease
- •Any evidence for existing metastatic disease (confirmed by CT Thorax/Abdomen, bone scan, or other methods according to clinical practice
- •Previous or concurrent treatment with cytotoxic agents for any reason (except non-oncological reasons)
- •Concurrent treatment with other experimental drugs and participation in another clinical trial with any investigational drug within 30 days prior to study entry
- •Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study/inadequate organ function
- •Reasons indicating risk of poor compliance
结局指标
主要结局
pCR rate after neoadjuvant treatment, defined as ypTis/ypN0, to be compared between all T-DXd treated patients versus standard-of- care (PAC+T+P or PAC/DOC+Carbo+T+P) (pooled across cohorts) Hypotheses: H0: pCR T-DXd = pCR standard-of-care H1: pCR T-DXd ≠ pCR standard-of-care
pCR rate after neoadjuvant treatment, defined as ypTis/ypN0, to be compared between all T-DXd treated patients versus standard-of- care (PAC+T+P or PAC/DOC+Carbo+T+P) (pooled across cohorts) Hypotheses: H0: pCR T-DXd = pCR standard-of-care H1: pCR T-DXd ≠ pCR standard-of-care
3-year distant disease-free survival (dDFS, according to STEEP 2.0 criteria) in T-DXd treated patients (pooled across cohorts) H0: 3-year dDFS rate in the T-DXd group < 92.0% H1: 3-year dDFS rate in the T-DXd group ≥ 92.0%
3-year distant disease-free survival (dDFS, according to STEEP 2.0 criteria) in T-DXd treated patients (pooled across cohorts) H0: 3-year dDFS rate in the T-DXd group < 92.0% H1: 3-year dDFS rate in the T-DXd group ≥ 92.0%
次要结局
- Clinical response after 6, 12, and 18 weeks of treatment by treatment and cohort
- 3-year dDFS in patients with pCR after neoadjuvant treatment without further chemotherapy
- pCR rates after different treatment durations (12 versus 18 weeks) to be compared by treatment in pooled cohorts
- interaction between treatment arm and risk cohort
- pCR rates in T-DXd12 weeks versus PAC+T+P in cohort 1
- pCR rates in T-DXd18 weeks versus PAC/DOC+Carbo+T+P in cohort 2
- STEEP 2.0 survival endpoints: - Invasive disease-free survival (IDFS) - Overall survival (OS) - Local recurrence-free survival (LRFS) - Breast cancer-free survival (BCFS) - Distant recurrence-free interval (DRFI) To be compared across T-DXd cohorts versus standard-of-care in pooled cohorts
- Change of health-related quality of life between baseline and after 1 year
研究者
Prof. Dr. med. Nadia Harbeck
Scientific
WSG Westdeutsche Studiengruppe GmbH
研究点 (45)
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