A Phase II Trial of Palbociclib in Combination With Trastuzumab and Endocrine Therapy in Patients With Previously-treated Locally Advanced or Metastatic HER2-positive Breast Cancer (PATRICIA II)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 73
- 试验地点
- 35
- 主要终点
- Progression-Free Survival at 6 months
研究概览
简要总结
PATRICIA is a phase II, open-label, multicentre, Simon's two-stage-design study of the combination of palbociclib plus trastuzumab, with or without letrozole, in post-menopausal patients with HER2-positive locally advanced or metastatic breast cancer (MBC) who have received chemotherapy and treatment with trastuzumab for their metastatic disease. Cohorts A, B1, and B2 based on their HR status and treatment allocation were planned.
Cohort A included patients with hormone receptor-negative, HER2 positive breast cancer, who received trastuzumab + palbociclib.
Cohort B1 included patients with hormone receptor-positive, HER2 positive breast cancer, who received trastuzumab + palbociclib.
Cohort B2 included patients with hormone receptor-positive, HER2 positive breast cancer, who received trastuzumab + palbociclib + letrozole.
The aim of the PATRICIA study is to test the hypothesis that the addition of Palbociclib to standard therapy is well tolerated and can provide a benefit in progression-free survival.
Based on interim results from this trial that support the benefit of CDK4 / 6 inhibition in luminal disease, two additional cohorts will be included.
详细描述
After the amendment of PATRICIA study, two additional cohorts will be included:
- Cohort C1: will include patients with OR+, HER2 positive, Luminal intrinsic subtype determined by PAM50 who will receive trastuzumab + palbociclib + endocrine therapy (ET)
- Cohort C2: will include patients with OR+, HER2 positive, Luminal intrinsic subtype determined by PAM50 who will receive treatment of physician's choice.
When the recruitment of those cohorts C begins, the recruitment in cohorts A and B will be closed.
For cohorts C, an adaptive design will be applied to compare arms of treatment in patients with Luminal subtype locally advanced or metastatic breast cancer (MBC).
All patients in those cohorts will have histologically- confirmed HR+/HER2-positive and PAM50-confirmed Luminal intrinsic subtype breast adenocarcinoma, and must have received at least 1 previous line of sistemic treatment for locally advanced disease or MBC which must have included trastuzumab and/or anti-HER2 Antibody-Drug conjugate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm B2:HER+/HR+: trastuzumab + palbociclib +letrozole (Recruitment Closed)
Patients with hormone receptor-positive, HER2 positive breast cancer, who received trastuzumab + palbociclib + letrozole Palbociclib: oral, 200 mg/day for 2 weeks, followed by 1 week off. Trastuzumab: intravenous trastuzumab loading dose of 8mg/kg followed by 6 mg/kg once every 3 weeks; or subcutaneous trastuzumab 600mg every 3 weeks.
Letrozole: daily oral dose of 2.5 mg.
干预措施: Endocrine therapy (Drug)
Arm A: HER2-positive/Hormone receptor-negative (Recruitment Closed)
Patients with hormone receptor-negative, HER2 positive breast cancer, who received trastuzumab + palbociclib.
Palbociclib: oral, 200 mg/day for 2 weeks, followed by 1 week off. Trastuzumab: intravenous trastuzumab loading dose of 8mg/kg followed by 6 mg/kg once every 3 weeks; or subcutaneous trastuzumab 600mg every 3 weeks.
干预措施: Palbociclib (Drug)
Arm A: HER2-positive/Hormone receptor-negative (Recruitment Closed)
Patients with hormone receptor-negative, HER2 positive breast cancer, who received trastuzumab + palbociclib.
Palbociclib: oral, 200 mg/day for 2 weeks, followed by 1 week off. Trastuzumab: intravenous trastuzumab loading dose of 8mg/kg followed by 6 mg/kg once every 3 weeks; or subcutaneous trastuzumab 600mg every 3 weeks.
干预措施: Trastuzumab (Drug)
Arm B1: HER2+/Hormone receptor-positive (Recruitment Closed)
Patients with hormone receptor-positive, HER2 positive breast cancer, who received trastuzumab + palbociclib.
Palbociclib: oral, 200 mg/day for 2 weeks, followed by 1 week off. Trastuzumab: intravenous trastuzumab loading dose of 8mg/kg followed by 6 mg/kg once every 3 weeks; or subcutaneous trastuzumab 600mg every 3 weeks.
干预措施: Palbociclib (Drug)
Arm B1: HER2+/Hormone receptor-positive (Recruitment Closed)
Patients with hormone receptor-positive, HER2 positive breast cancer, who received trastuzumab + palbociclib.
Palbociclib: oral, 200 mg/day for 2 weeks, followed by 1 week off. Trastuzumab: intravenous trastuzumab loading dose of 8mg/kg followed by 6 mg/kg once every 3 weeks; or subcutaneous trastuzumab 600mg every 3 weeks.
干预措施: Trastuzumab (Drug)
Arm B2:HER+/HR+: trastuzumab + palbociclib +letrozole (Recruitment Closed)
Patients with hormone receptor-positive, HER2 positive breast cancer, who received trastuzumab + palbociclib + letrozole Palbociclib: oral, 200 mg/day for 2 weeks, followed by 1 week off. Trastuzumab: intravenous trastuzumab loading dose of 8mg/kg followed by 6 mg/kg once every 3 weeks; or subcutaneous trastuzumab 600mg every 3 weeks.
Letrozole: daily oral dose of 2.5 mg.
干预措施: Palbociclib (Drug)
Arm B2:HER+/HR+: trastuzumab + palbociclib +letrozole (Recruitment Closed)
Patients with hormone receptor-positive, HER2 positive breast cancer, who received trastuzumab + palbociclib + letrozole Palbociclib: oral, 200 mg/day for 2 weeks, followed by 1 week off. Trastuzumab: intravenous trastuzumab loading dose of 8mg/kg followed by 6 mg/kg once every 3 weeks; or subcutaneous trastuzumab 600mg every 3 weeks.
Letrozole: daily oral dose of 2.5 mg.
干预措施: Trastuzumab (Drug)
Arm C1: Palbociclib, trastuzumab and endocrine therapy
HR-positive, HER2 positive, Luminal intrinsic subtype determined by PAM50 who will receive trastuzumab + palbociclib + endocrine therapy
Trastuzumab: intravenous trastuzumab loading dose of 8mg/kg followed by 6 mg/kg once every 3 weeks; or subcutaneous trastuzumab 600mg every 3 weeks.
Palbociclib: oral, 125 mg/d for 3 weeks, followed by one week off, in 4-week cycles.
Endocrine therapy: either an Aromatase Inhibitor, Fulvestrant, or Tamoxifen.
干预措施: Palbociclib (Drug)
Arm C1: Palbociclib, trastuzumab and endocrine therapy
HR-positive, HER2 positive, Luminal intrinsic subtype determined by PAM50 who will receive trastuzumab + palbociclib + endocrine therapy
Trastuzumab: intravenous trastuzumab loading dose of 8mg/kg followed by 6 mg/kg once every 3 weeks; or subcutaneous trastuzumab 600mg every 3 weeks.
Palbociclib: oral, 125 mg/d for 3 weeks, followed by one week off, in 4-week cycles.
Endocrine therapy: either an Aromatase Inhibitor, Fulvestrant, or Tamoxifen.
干预措施: Trastuzumab (Drug)
Arm C1: Palbociclib, trastuzumab and endocrine therapy
HR-positive, HER2 positive, Luminal intrinsic subtype determined by PAM50 who will receive trastuzumab + palbociclib + endocrine therapy
Trastuzumab: intravenous trastuzumab loading dose of 8mg/kg followed by 6 mg/kg once every 3 weeks; or subcutaneous trastuzumab 600mg every 3 weeks.
Palbociclib: oral, 125 mg/d for 3 weeks, followed by one week off, in 4-week cycles.
Endocrine therapy: either an Aromatase Inhibitor, Fulvestrant, or Tamoxifen.
干预措施: Endocrine therapy (Drug)
Arm C2: Treatment based of physician's choice
HR-positive, HER2 positive, Luminal intrinsic subtype determined by PAM50 who will receive treatment based on physician's choice from the following options: TDM1 or chemotherapy (gemcitabine, vinorelbine, capecitabine, eribulin or a taxane) in combination with trastuzumab or endocrine therapy (Aromatase Inhibitor, Fulvestrant or Tamoxifen) in combination with trastuzumab.
干预措施: Trastuzumab (Drug)
Arm C2: Treatment based of physician's choice
HR-positive, HER2 positive, Luminal intrinsic subtype determined by PAM50 who will receive treatment based on physician's choice from the following options: TDM1 or chemotherapy (gemcitabine, vinorelbine, capecitabine, eribulin or a taxane) in combination with trastuzumab or endocrine therapy (Aromatase Inhibitor, Fulvestrant or Tamoxifen) in combination with trastuzumab.
干预措施: Endocrine therapy (Drug)
Arm C2: Treatment based of physician's choice
HR-positive, HER2 positive, Luminal intrinsic subtype determined by PAM50 who will receive treatment based on physician's choice from the following options: TDM1 or chemotherapy (gemcitabine, vinorelbine, capecitabine, eribulin or a taxane) in combination with trastuzumab or endocrine therapy (Aromatase Inhibitor, Fulvestrant or Tamoxifen) in combination with trastuzumab.
干预措施: Chemotherapy (Drug)
Arm C2: Treatment based of physician's choice
HR-positive, HER2 positive, Luminal intrinsic subtype determined by PAM50 who will receive treatment based on physician's choice from the following options: TDM1 or chemotherapy (gemcitabine, vinorelbine, capecitabine, eribulin or a taxane) in combination with trastuzumab or endocrine therapy (Aromatase Inhibitor, Fulvestrant or Tamoxifen) in combination with trastuzumab.
干预措施: Antibody-Drug Conjugates (Drug)
结局指标
主要结局
Progression-Free Survival at 6 months
时间窗: From randomization date to date of first documentation of progression or death , whichever came first, assessed up to 6 months.
For cohorts A,B1 and B2: This was defined as the proportion of patients alive and without progression (according to RECIST v1.1 criteria), 6 months after randomization.
Progression-Free Survival (PFS)as Assessed by the Investigator [ Time Frame: From randomization date to date of first documentation of progression or death
时间窗: From randomization date to date of first documentation of progression or death , whichever came first, assessed up to 4 years
For cohorts C: This will be defined as the proportion of patients alive and without progression (according to RECIST v1.1 criteria)
次要结局
- Rate of Overall tumour objective response rate (ORR) in treatment arms (A and B).(up to 5 years)
- Rate of Disease control rate (DCR) in treatment arms (A and B)(up to 5 years)
- Evaluation of time to progression (Cohorts A and B)(up to 5 years)
- Cardiac Safety profile in arms A and B: Percentage of Participants with cardiac adverse events(up to 5 years)
- Overall Survival in treatment arms (Cohorts A and B).(up to 5 years)
- Rate of Disease control rate (DCR) in both treatment arms (C1 and C2)(up to 4 years)
- Rate of Overall tumour objective response rate (ORR) in treatment arms (C1 and C2).(up to 4 years)
- Median duration of response in both treatment arms (C1 and C2).(up to 4 years)
- Change From Baseline Between Treatment Comparison in Functional Assessment of Cancer Therapy FACT-B to assess patient reported breast cancer specific health related quality of life (HRQOL) and general health status in both treatment arms (C1 and C2).(From the date of randomization up to 5 years)
- Change From Baseline Between Treatment Comparison in Euroqol-5D (EQ-5D) to assess patient reported breast cancer specific health related quality of life (HRQOL) and general health status in both treatment arms (C1 and C2).(From the date of randomization up to 5 years)
- Safety profile in all treatment arms: Percentage of Participants with Adverse Events(up to 5 years)
- To investigate biomarkers as predictors of response or resistance to the study treatment.(up to 5 years)