2024-518026-32-00招募中3 期
Atezolizumab, Pertuzumab and Trastuzumab with chemotherapy as neoadjuvant treatment of HER2 positive early high-risk and locally advanced breast cancer (APTneo)
Fondazione Michelangelo62 个研究点 分布在 4 个国家目标入组 646 人开始时间: 2024年11月21日最近更新:
适应症
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 646
- 试验地点
- 62
- 主要终点
- Event Free Survival (EFS)
研究概览
简要总结
Compare 5-year Event-Free Survival (EFS) between Arm B (B1+B2) and Arm A. Depending on the superiority of the primary efficacy endpoint (EFS), a formal comparison of Arm B1 vs Arm A, Arm B2 vs Arm A will be conducted. Comparison of Arm B1 vs Arm B2 will be conducted in an exploratory manner
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 主要目的
- Follow-up
- 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 aged 18 years or older with early high-risk ((T1cN1; T2N1; T3N0) or locally advanced and inflammatory breast cancers (stage III A-C according to AJCC) suitable for neoadjuvant treatment
- •Willing and able to comply with the protocol
- •Histologically confirmed unilateral invasive breast cancer
- •HER2 positive disease according to ASCO/CAP current guidelines
- •Known estrogen (ER) and progesterone receptor (PgR)
- •Availability of a representative paraffin-embedded (FFPE) tumor block taken at diagnostic biopsy for central confirmation of HER2 eligibility, for assessment of ER, PgR, Ki67 and PD-L1 expression and for biomarker evaluation is mandatory
- •Consent to the collection of blood samples mandatorily before starting neoadjuvant treatment, after the first cycle of therapy, at the end of neoadjuvant treatment (before surgery), 6 months after surgery and at the end of all treatments.
- •ECOG performance status 0 or 1
- •For women who are not postmenopausal (≥ 12 months of non-therapyinduced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 7 months after the last dose of study drugs. Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. Examples of contraceptive methods with a failure rate of < 1% per year include tubal ligation, male sterilization (not acceptable in Germany), hormonal implants, established, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices
- •Written informed consent to participate in the trial (approved by the Institutional Review Board [IRB]/ Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures
排除标准
- •Evidence of bilateral breast cancer or metastatic disease (M1)
- •History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins or hyaluronidase; only for patients enrolled in Germany: history of severe allergic reactions to any protocol anticancer agent or any of the excipients
- •Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
- •Patients with prior allogeneic stem cell or solid organ transplantation
- •History of autoimmune disease including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Bell’s palsy, GuillainBarré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis (see Appendix A for preexisting autoimmune diseases and immune deficiencies)
- •History of idiopathic pulmonary fibrosis (including bronchiolitis obliterans with organizing pneumonia) or evidence of active pneumonitis on screening chest computed tomography scan
- •Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease
- •History of HIV infection, active hepatitis B (chronic or acute), or hepatitis C infection. Patients with past or resolved hepatitis B infection (defined as having a negative HBsAg test and a positive hepatitis B core antibody [anti-HBc] test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction assay (PCR) is negative for HCV RNA Only for patients enrolled in Germany: all patients have to undergo hepatitis and HIV testing during screening in order to adequately determine the infection status and ensure that patients with an active infection will be excluded from the trial.
- •Active tuberculosis
- •Severe infections within 4 weeks prior to Day 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia. Signs or symptoms of significant infection within 2 weeks prior to Day 1
- •Received oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1
- •Patients with HER2-negative defined as 0-1+ by immunohistochemistry or 2+ by immunohistochemistry without HER2 amplification by either In Situ Hybridization (ISH) or other amplification tests done locally are considered not eligible for the study
- •Other serious illness or medical condition, including but not limited to history of documented congestive cardiac failure; New York Heart Association (NYHA) Class II or greater CHF; angina pectoris requiring anti-anginal medication or unstable angina within 6 months prior to Day 1; evidence of transmural infarction on ECG; myocardial infarction stroke or transient ischemic attack (TIA) within 6 months prior to Day 1; poorly controlled hypertension (e.g. systolic >180 mm Hg or diastolic >100 mm Hg; however, patients with hypertension which is well controlled on medication are eligible); clinically significant valvular heart disease; high-risk uncontrolled arrhythmias; severe dyspnea at rest requiring supplementary oxygen therapy; uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently); Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected calcium > ULN)
- •Patients with a history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and precluding informed consent or adversely affecting compliance with study drugs
- •Serious uncontrolled infections (bacterial or viral) or poorly controlled diabetes mellitus
- •Any of the following abnormal baseline hematological values: a. White blood count (WBC) < 2.5 x 109 /L b. Absolute Neutrophil Count (ANC) < 1.5 × 109 /L c. Lymphocyte count < 0.5 x 109 /L d. Platelet count < 100 × 109 /L e. Hemoglobin (Hb) < 10 g/dL
- •Any of the following abnormal baseline laboratory tests a. Serum total bilirubin > 1.5 × ULN (upper limit of normal) (except for patients with clearly documented Gilbert’s syndrome) b. Alanine transaminase (ALT) or aspartate transaminase (AST) > 1.25 × ULN c. Alkaline phosphatase > 2.5× ULN d. Serum creatinine > 1.5 × ULN e. INR and aPTT > 1.5 × ULN within 2 weeks prior to enrollment. This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose
- •Baseline left ventricular ejection fraction (LVEF) < 55% by echocardiography or multi-gated scintigraphic scan (MUGA)
- •Major surgical procedure within 28 days prior to Day 1 or anticipation of need for a major surgical procedure during the course of the study
- •Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist®) within 4 weeks prior to Day 1 or at any time during the study; only for patients enrolled in Germany: the concomitant administration of yellow-fever vaccine is not allowed.
- •Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti−CTLA-4, anti−PD-1, and anti−PD-L1 therapeutic antibodies
- •Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment
- •Pregnant or lactating women. Documentation of a negative pregnancy test must be available for premenopausal women with intact reproductive organs and for women less than one year after the last menstrual cycle
- •Women with childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception as mentioned at point
- •of inclusion criteria
- •Previous treatment with chemotherapy, hormonal therapy or an investigational drug for any type of malignancy; only for patients enrolled in Germany: presence of bleeding tumors.
- •Previous investigational treatment for any condition other than malignancy within 4 weeks of randomization date; only for patients enrolled in Germany: or within 5 half-lives, whichever is longer.
- •Administration of a live, attenuated vaccine within 4 weeks before Day 1 or anticipation that such a live attenuated vaccine will be required during the study
- •Previous or concomitant malignancy of any other type that could affect compliance with the protocol or interpretation of results. Patients with curatively treated basal cell carcinoma of the skin or in situ cervix cancer are eligible
- •Pre-existing motor or sensory neuropathy of grade > 1 for any reason
结局指标
主要结局
Event Free Survival (EFS)
Event Free Survival (EFS)
次要结局
- Distant Event Free Survival
- Overall Survival
- Pathological Complete Response (pCR)
- Relationship between pCR and EFS
- Clinical Overall Response (cOR) at the end of neo-adjuvant treatment
- Disease-Free Survival (DFS)
研究者
Board of Directors’ designee
Scientific
Fondazione Michelangelo
研究点 (62)
Loading locations...
相似试验
进行中（未招募）
1 期
Atezolizumab, Pertuzumab and Trastuzumab with chemotherapy as neoadjuvant (before surgery) treatment of HER2 positive early high-risk and locally advanced breast cancer.Women with a diagnosis of non-metastatic high-risk invasive unilateral, HER2-positive breast cancer.MedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)EUCTR2017-000981-31-BEFONDAZIONE MICHELANGELO ONLUS PER L'AVANZAMENTO DELLO STUDIO E LA CURA DEI TUMORI650
进行中（未招募）
1 期
Atezolizumab, Pertuzumab and Trastuzumab with chemotherapy as neoadjuvant (before surgery) treatment of HER2 positive early high-risk and locally advanced breast cancer.EUCTR2017-000981-31-ATFONDAZIONE MICHELANGELO ONLUS PER L'AVANZAMENTO DELLO STUDIO E LA CURA DEI TUMORI650
进行中（未招募）
1 期
Atezolizumab, Pertuzumab and Trastuzumab with chemotherapy as neoadjuvant (before surgery) treatment of HER2 positive early high-risk and locally advanced breast cancerWomen with a diagnosis of non metastatic high-risk invasive unilateral, HER2-positive breast cancerMedDRA version: 20.0Level: LLTClassification code 10006283Term: Breast neoplasm malignant femaleSystem Organ Class: 100000004864EUCTR2017-000981-31-ITFONDAZIONE MICHELANGELO ONLUS PER L'AVANZAMENTO DELLO STUDIO E LA CURA DEI TUMORI650
进行中（未招募）
1 期
Atezolizumab, Pertuzumab and Trastuzumab with chemotherapy as neoadjuvant (before surgery) treatment of HER2 positive early high-risk and locally advanced breast cancer.Women with a diagnosis of non-metastatic high-risk invasive unilateral, HER2-positive breast cancer.MedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)EUCTR2017-000981-31-ROFONDAZIONE MICHELANGELO ONLUS PER L'AVANZAMENTO DELLO STUDIO E LA CURA DEI TUMORI650
尚未招募
不适用
eoadjuvant trastuzumab, pertuzumab and tucatinib without chemotherapy in HER2-positive breast cancer: the TRAIN-4 studyBreast cancerNL-OMON53609Antoni van Leeuwenhoek Ziekenhuis30