National Phase IIIb Prospective Two-Cohort Non-Randomized, Multi-centre, Open Label Study to Assess the Safety of Subcutaneous Trastuzumab and Molecular Biomarkers in Patients With Early and Locally Advanced HER2-Positive Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 240
- 试验地点
- 54
- 主要终点
- Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
This non-randomized, multicenter, open-label study will assess the safety and efficacy of subcutaneously administered trastuzumab in participants with early and locally advanced HER2-positive breast cancer in two sequential cohorts. First 120 participants will be treated with subcutaneous (SC) trastuzumab 600 milligrams (mg) vial (Cohort A) and the subsequent 120 participants will be treated with SC trastuzumab prefilled single use injection device (SID) (Cohort B). Participants from each cohort will receive neoadjuvant or adjuvant chemotherapy consisting of doxorubicin every 3 weeks (q3w) (1 cycle) for 4 cycles followed by paclitaxel weekly or docetaxel every 3 weeks (q3w) in combination with SC trastuzumab (600 mg) q3w for 4 cycles and a further 14 cycles of SC trastuzumab (600 mg) q3w alone. All participants will be followed up for 24 months after the last participant has received the last dose of study treatment, or earlier in case of withdrawal from the study, loss to follow-up or death.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast. Stage of disease: T1-4 (T describes size of tumour from 1 to 4), N0-3 (N describes nearby lymph nodes), M0 (M describes distant metastasis)
- •HER2-positive disease immunohistochemistry (IHC) 3+ or in situ hybridization (ISH) positive
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Left ventricular ejection fraction (LVEF) of greater than or equal to (>=) 55 percent (%) measured by echocardiography (ECHO) or multiple gated acquisition (MUGA) scan prior to first dose of trastuzumab SC
- •Intact skin at site of SC injection on the thigh
排除标准
- •History of other malignancy, except for participants with curatively treated carcinoma in situ of the cervix or basal cell carcinoma and participants with other curatively treated malignancies, other than breast cancer, who have been disease-free for at least 5 years
- •Severe dyspnea at rest or requiring supplementary oxygen therapy
- •Concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness
- •Serious cardiac illness or medical conditions that would preclude the use of trastuzumab, specifically: history of documented congestive heart failure (CHF), high-risk uncontrolled arrhythmias, angina pectoris requiring medication, clinically significant valvular disease, evidence of transmural infarction on electrocardiogram (ECG), diagnosed poorly controlled hypertension
- •Known infection with human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or hepatitis C virus (HCV)
- •Pregnant or lactating women
- •Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment, including hormonal therapy, bisphosphonate therapy and immunotherapy, within 28 days prior to the first dose of study treatment
- •Known hypersensitivity to trastuzumab, murine proteins, to any of the excipients of Herceptin including hyaluronidase, or the adhesive of the SC device (for Cohort B), or a history of severe allergic or immunological reactions, for example, difficulty to control asthma
- •Inadequate bone marrow, hepatic or renal function
- •Hormonal treatment concomitant with chemotherapy (allowed in adjuvant phase with adjuvant trastuzumab SC)
- •Pre-existing motor or sensory neuropathy of Grade greater than (>) 1
- •Synchronous bilateral invasive breast cancer
研究组 & 干预措施
Trastuzumab (Vial)
Participants will receive trastuzumab 600 mg SC using a vial q3w (1 cycle) for 1 year (4 cycles in combination with adjuvant or neoadjuvant chemotherapy [consisting of doxorubicin, paclitaxel or docetaxel] and 14 cycles administered alone).
干预措施: Doxorubicin (Drug)
Trastuzumab (Vial)
Participants will receive trastuzumab 600 mg SC using a vial q3w (1 cycle) for 1 year (4 cycles in combination with adjuvant or neoadjuvant chemotherapy [consisting of doxorubicin, paclitaxel or docetaxel] and 14 cycles administered alone).
干预措施: Docetaxel (Drug)
Trastuzumab (Vial)
Participants will receive trastuzumab 600 mg SC using a vial q3w (1 cycle) for 1 year (4 cycles in combination with adjuvant or neoadjuvant chemotherapy [consisting of doxorubicin, paclitaxel or docetaxel] and 14 cycles administered alone).
干预措施: Paclitaxel (Drug)
Trastuzumab (Vial)
Participants will receive trastuzumab 600 mg SC using a vial q3w (1 cycle) for 1 year (4 cycles in combination with adjuvant or neoadjuvant chemotherapy [consisting of doxorubicin, paclitaxel or docetaxel] and 14 cycles administered alone).
干预措施: Trastuzumab (Drug)
Trastuzumab (SID)
Participants will receive trastuzumab 600 mg SC using SID q3w (1 cycle) for 1 year (4 cycles in combination with adjuvant or neoadjuvant chemotherapy [consisting of doxorubicin, paclitaxel or docetaxel] and 14 cycles administered alone).
干预措施: Doxorubicin (Drug)
Trastuzumab (SID)
Participants will receive trastuzumab 600 mg SC using SID q3w (1 cycle) for 1 year (4 cycles in combination with adjuvant or neoadjuvant chemotherapy [consisting of doxorubicin, paclitaxel or docetaxel] and 14 cycles administered alone).
干预措施: Docetaxel (Drug)
Trastuzumab (SID)
Participants will receive trastuzumab 600 mg SC using SID q3w (1 cycle) for 1 year (4 cycles in combination with adjuvant or neoadjuvant chemotherapy [consisting of doxorubicin, paclitaxel or docetaxel] and 14 cycles administered alone).
干预措施: Paclitaxel (Drug)
Trastuzumab (SID)
Participants will receive trastuzumab 600 mg SC using SID q3w (1 cycle) for 1 year (4 cycles in combination with adjuvant or neoadjuvant chemotherapy [consisting of doxorubicin, paclitaxel or docetaxel] and 14 cycles administered alone).
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: Day 1 up to 28 days after last dose of trastuzumab (up to approximately 1 year)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were the AEs occurring from starting on the day of or after first administration of trastuzumab and within 28 days after last dose of trastuzumab. Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.
次要结局
- Percentage of Participants With Pathological Complete Response (pCR) (Neoadjuvant Groups Only) Using Mammography(Day 1 up to 24 weeks)
- Duration of Treatment With Trastuzumab(Day 1 up last dose of trastuzumab (up to approximately 1 year))
- Percentage of Participants Who Received Concomitant Medications(Screening (Day -28 to -1) up to 2.5 years)
- Actual Dose of Trastuzumab Administered(Day 1 up last dose of trastuzumab (up to approximately 1 year))
- Percentage of Participants With Event (Local, Regional or Distant Recurrence, Contralateral Breast Cancer or Death) Using Mammography(Day 1 up to local, regional or distant recurrence, contralateral breast cancer or death due to any cause (whichever occurred first [up to approximately 4.5 years]))
- Disease-Free Survival (DFS) Using Mammography(Day 1 up to local, regional or distant recurrence, contralateral breast cancer or death due to any cause (whichever occurred first [up to approximately 4.5 years]))
- Percentage of Participants Who Died(Day 1 up to death due to any cause (up to approximately 4.5 years))
- Overall Survival (OS)(Day 1 up to death due to any cause (up to approximately 4.5 years))
- Percentage of Participants by Response to Patient Satisfaction Questionnaire (PSQ)(After at least 14 cycles (1 cycle = 21 days; maximum up to 1 year))
- Percentage of Health Care Professionals (HCPs) by Response to Health Care Professional Questionnaire (HCPQ)(After at least 4 participants completed 5 cycles of adjuvant treatment (1 cycle = 21 days; maximum up to 1 year))