A Randomized, Multicenter, Open-Label Cross-Over Study to Evaluate Patient Preference and Satisfaction of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Patients With HER2-Positive Early Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 160
- 试验地点
- 40
- 主要终点
- Percentage of Participants by Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 1 of the Patient Preference Questionnaire (PPQ)
研究概览
简要总结
This is a Phase II, randomized, multicentre, multinational, open-label, cross-over study in adult patients who have completed neoadjuvant chemotherapy with neoadjuvant pertuzumab and trastuzumab and have undergone surgical treatment of human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. The study will consist of two adjuvant treatment periods: a treatment cross-over period and a treatment continuation period. It will evaluate participant-reported preference for a subcutaneously administered fixed-dose combination formulation (FDC SC) of pertuzumab and trastuzumab compared with intravenously (IV) administered pertuzumab and trastuzumab formulations. The study will also evaluate participant-reported satisfaction with pertuzumab and trastuzumab FDC SC and health-related quality of life outcomes; healthcare professionals' perceptions of time/resource use and convenience of pertuzumab and trastuzumab FDC SC compared with pertuzumab and trastuzumab IV formulations; as well as the safety and efficacy of each study regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- •Disease-specific criteria:
- •Female or male with histologically confirmed, HER2-positive (HER2+) inflammatory, locally advanced or early-stage breast cancer who have received neoadjuvant pertuzumab and trastuzumab and have completed neoadjuvant chemotherapy and subsequently undergone surgery for their breast cancer.
- •HER2+ breast cancer assessed at the local laboratory prior to initiation of neoadjuvant therapy. HER2+ status must be determined based on breast biopsy material obtained prior to neoadjuvant treatment and is defined as 3+ by immunohistochemistry (IHC) and/or positive by HER2 amplification by in situ hybridization (ISH) with a ratio of ≥2 for the number of HER2 gene copies to the number of chromosome 17 copies.
- •Hormone receptor status of the primary tumour determined by local assessment. Hormone receptor status may be either positive or negative.
- •Completed all neoadjuvant chemotherapy and surgery. Adjuvant radiotherapy may be planned or ongoing at study entry and adjuvant hormone therapy is allowed during the study. Note that study treatment cannot be initiated within <2 weeks of surgery but must be initiated ≤9 weeks from the last administration of systemic neoadjuvant therapy.
- •No evidence of residual, locally recurrent or metastatic disease after completion of surgery. Patients with clinical suspicion of metastases must undergo radiological assessments per institutional practice to rule out distant disease.
- •Wound healing after breast cancer surgery adequate per investigator's assessment to allow initiation of study treatment within ≤9 weeks of last systemic neoadjuvant therapy
- •No adjuvant chemotherapy planned. Note that adjuvant hormonal treatment is allowed during the study.
- •General criteria:
- •Ability to comply with the study protocol, in the investigator's judgment
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Intact skin at planned site of subcutaneous injections (thigh)
- •Left ventricular ejection fraction (LVEF) ≥55% measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan within 28 days of study randomization
- •No major surgical procedure unrelated to breast cancer within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
- •For women of childbearing potential: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating eggs, Women must remain abstinent or use non-hormonal contraceptive methods with a failure rate of <1% per year, or two effective non-hormonal contraceptive methods during the study treatment periods and for 7 months after the last dose of study treatment
- •For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm, men must remain abstinent or use a condom during the study treatment periods and for seven months after the last dose of study treatment to avoid exposing the embryo. Men must refrain from donating sperm during this same period
- •A negative serum pregnancy test must be available prior to randomization for women of childbearing potential
排除标准
- •Cancer-specific criteria:
- •Stage IV (metastatic) breast cancer
- •Current or prior history of active malignancy within the last five years. Appropriately treated non-melanoma skin cancer; in situ carcinomas, including cervix, colon, or skin; or Stage I uterine cancer within the last five years are allowed
- •Previous systemic therapy for treatment or prevention of breast cancer, except neoadjuvant Perjeta, Herceptin and chemotherapy for current breast cancer
- •General criteria:
- •Investigational treatment within four weeks of enrolment
- •Serious cardiac illness or medical conditions
- •History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease, coronary heart disease, clinically significant electrolyte abnormalities, or family history of sudden unexplained death or long QT syndrome
- •Inadequate bone marrow, renal and impaired liver function
- •Current severe, uncontrolled systemic disease that may interfere with planned treatment
- •Pregnant or breastfeeding, or intending to become pregnant during the study or within seven months after the last dose of study treatment. Women of childbearing potential must have a negative serum pregnancy test result within seven days prior to initiation of study treatment
- •Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in, and completion of, the study
- •Known active liver disease, for example, active viral hepatitis infection, autoimmune hepatic disorders, or sclerosing cholangitis
- •Concurrent, serious, uncontrolled infections, or known infection with human immunodeficiency virus (HIV)
- •Known hypersensitivity to any of the study drugs, excipients, and/or murine proteins
- •Current chronic daily treatment with corticosteroids
研究组 & 干预措施
A: P+H IV Followed by PH FDC SC
In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.
干预措施: Pertuzumab and Trastuzumab Fixed-Dose Combination for Subcutaneous Administration (PH FDC SC) (Drug)
A: P+H IV Followed by PH FDC SC
In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.
干预措施: Pertuzumab IV (Drug)
A: P+H IV Followed by PH FDC SC
In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.
干预措施: Trastuzumab IV (Drug)
B: PH FDC SC Followed by P+H IV
In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.
干预措施: Pertuzumab and Trastuzumab Fixed-Dose Combination for Subcutaneous Administration (PH FDC SC) (Drug)
B: PH FDC SC Followed by P+H IV
In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.
干预措施: Pertuzumab IV (Drug)
B: PH FDC SC Followed by P+H IV
In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.
干预措施: Trastuzumab IV (Drug)
结局指标
主要结局
Percentage of Participants by Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 1 of the Patient Preference Questionnaire (PPQ)
时间窗: Cycle 6 Day 1 (each cycle is 21 days)
Question 1 of the Patient Preference Questionnaire (PPQ) asked participants the following question: "All things considered, which method of administration did you prefer?" The three available options for a participant's response were: IV, SC, or No preference. A point estimate with associated exact Clopper-Pearson binomial 95% confidence interval was calculated only for the percentage of participants who preferred PH FDC SC.
次要结局
- Change From Baseline Over Time in the Insomnia Scale Score of the EORTC QLQ-C30(Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years))
- Change From Baseline Over Time in the Appetite Loss Scale Score of the EORTC QLQ-C30(Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years))
- Change From Baseline Over Time in the Constipation Scale Score of the EORTC QLQ-C30(Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years))
- Change From Baseline Over Time in the Financial Difficulties Scale Score of the EORTC QLQ-C30(Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years))
- Mean Scores of the Five Domains of the TASQ-IV and TASQ-SC (Satisfaction, Physical Impact, Psychological Impact, Impact on Activities of Daily Living, and Convenience) to Assess the Impact of IV and SC Routes of Administration(Cycle 3 Day 1, Cycle 6 Day 1 (each cycle is 21 days))
- Percentage of Participants by Their Responses to Question 9 of the TASQ-IV and TASQ-SC, Assessing Whether Participants Receiving IV and SC Administration Have as Much Time as They Would Like to Talk to Their Nurse and/or Doctor About Their Illness(Cycle 3 Day 1 and Cycle 6 Day 1 (each cycle is 21 days))
- Percentage of Participants by Their Responses to Question 10 of the TASQ-IV and TASQ-SC, Assessing Whether IV and SC Administration Have an Impact on the Amount of Time Participants Have to Talk to Their Nurse and/or Doctor About Their Illness(Cycle 3 Day 1 and Cycle 6 Day 1 (each cycle is 21 days))
- Percentage of Participants by Their Responses to Question 11 of the TASQ-IV and TASQ-SC, Assessing the Participants' Preferred Method for Receiving Cancer Treatment(Cycle 3 Day 1 and Cycle 6 Day 1 (each cycle is 21 days))
- Percentage of Participants by Their Choice of Treatment in the Treatment Continuation Period (PH FDC SC or P+H IV) and by Consistency of This Choice With Their Preferred Method of Administration Reported in Question 1 of the PPQ(Cycle 6 Day 1 (each cycle is 21 days))
- Percentage of Responses From Participants to the Two Main Reasons for Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 3 of the Patient Preference Questionnaire (PPQ)(Cycle 6 Day 1 (each cycle is 21 days))
- Percentage of Participants by Responses to the Strength of Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 2 of the Patient Preference Questionnaire (PPQ)(Cycle 6 Day 1 (each cycle is 21 days))
- Percentage of Participants by Their Level of Satisfaction With the Respective Methods of Administration (IV and SC), Question 1 of the Therapy Administration Satisfaction Questionnaire -Intravenous (TASQ-IV) and -Subcutaneous (TASQ-SC)(Cycle 3 Day 1, Cycle 6 Day 1 (each cycle is 21 days))
- Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room(Day 1 of Cycles 1-6 (each cycle is 21 days))
- Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room(Day 1 of Cycle 6 (each cycle is 21 days))
- Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room(Day 1 of Cycle 6 (each cycle is 21 days))
- Percentage of Healthcare Professionals (HCPs) by Their Responses to Question 8 of the HCPQ - Treatment Room(Day 1 of Cycle 6 (each cycle is 21 days))
- Duration of Treatment Preparation According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the HCPQ - Drug Preparation Room(Day 1 of Cycles 1-6 (each cycle is 21 days))
- Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room(Day 1 of Cycle 6 (each cycle is 21 days))
- Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use of Each Study Regimen, Questions 3 and 4 of the HCPQ - Drug Preparation Room(Day 1 of Cycle 6 (each cycle is 21 days))
- Change From Baseline Over Time in Health-Related Quality of Life (HRQoL) as Assessed by the Global Health Status (GHS)/HRQoL Scale Score of the the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30)(Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years))
- Change From Baseline Over Time in the Physical Functioning Scale Score of the EORTC QLQ-C30(Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years))
- Change From Baseline Over Time in the Role Functioning Scale Score of the EORTC QLQ-C30(Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years))
- Change From Baseline Over Time in the Emotional Functioning Scale Score of the EORTC QLQ-C30(Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years))
- Change From Baseline Over Time in the Cognitive Functioning Scale Score of the EORTC QLQ-C30(Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years))
- Change From Baseline Over Time in the Social Functioning Scale Score of the EORTC QLQ-C30(Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years))
- Change From Baseline Over Time in the Fatigue Scale Score of the EORTC QLQ-C30(Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years))
- Change From Baseline Over Time in the Nausea and Vomiting Scale Score of the EORTC QLQ-C30(Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years))
- Change From Baseline Over Time in the Pain Scale Score of the EORTC QLQ-C30(Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years))
- Change From Baseline Over Time in the Dyspnoea Scale Score of the EORTC QLQ-C30(Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years))
- Change From Baseline Over Time in the Diarrhoea Scale Score of the EORTC QLQ-C30(Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years))
- Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received(From Day 1 of Cycle 1 to the end of Cycle 3 of Cross-Over Period; from Day 1 of Cycle 4 to the end of Cycle 6 of Cross-Over Period (1 cycle is 21 days))
- Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods(From Day 1 of Cycle 1 to end of Cycle 6 of the Treatment Cross-Over Period; from Day 1 of Cycle 7 up to the completion of 18 cycles of neo/adjuvant anti-HER2 treatment in the Treatment Continuation Period (1 cycle is 21 days))
- Number of Participants With at Least One Event of Heart Failure With the FDC SC and IV Formulations During the Treatment Cross-Over and Treatment Continuation Periods(From Day 1 of Cycle 1 to end of Cycle 6 of the Treatment Cross-Over Period; from Day 1 of Cycle 7 up to the completion of 18 cycles of neo/adjuvant anti-HER2 treatment in the Treatment Continuation Period (1 cycle is 21 days))
- Number of Participants With an Event for Invasive Disease-Free Survival Including Second Primary Non-Breast Cancer, Overall and by Treatment Sequence(Up to 3 years, 10 months)
- Number of Participants With at Least One Event of Ejection Fraction Decreased With the FDC SC and IV Formulations During the Treatment Cross-Over and Treatment Continuation Periods(Baseline; Day 1 of Cycles 4, 7, and 11 (each cycle is 21 days); End of Treatment Visit (up to 1 year))
- Number of Participants With an Event for Overall Survival, Overall and by Treatment Sequence(Up to 3 years, 10 months)
- Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Overall Survival, Overall and by Treatment Sequence(At 12, 24, and 36 months)
- Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Invasive Disease-Free Survival Including Second Primary Non-Breast Cancer, Overall and by Treatment Sequence(At 12, 24, and 36 months)
- Number of Participants With an Event for Invasive Disease-Free Survival, Overall and by Treatment Sequence(Up to 3 years, 10 months)
- Number of Participants With Targeted Vital Signs Outside the Normal Limits Among Those Without an Abnormality at Baseline During the Treatment Cross-Over and Treatment Continuation Periods(Pre-dose at Day 1 of Cycles 1 (baseline), 4, and 7, and end of treatment (up to 18 cycles; 1 cycle is 21 days))
- Number of Participants With Chemistry and Hematology Laboratory Test Result Shifts From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 Post-Baseline During the Treatment Cross-Over and Treatment Continuation Periods(Pre-dose at Day 1 of Cycles 1 (baseline), 4, 7, 11, 15, and end of treatment (up to 18 cycles; 1 cycle is 21 days))
- Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Invasive Disease-Free Survival, Overall and by Treatment Sequence(At 12, 24, and 36 months)
- Number of Participants With an Event for Distant Disease-Free Survival, Overall and by Treatment Sequence(Up to 3 years, 10 months)
- Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Distant Disease-Free Survival, Overall and by Treatment Sequence(At 12, 24, and 36 months)