Study of Palbociclib and Trastuzumab With Endocrine Therapy in HER2-positive Metastatic Breast Cancer
- Conditions
- Metastatic Breast Cancer
- Interventions
- Drug: Endocrine therapyDrug: ChemotherapyDrug: Antibody-Drug Conjugates
- Registration Number
- NCT02448420
- Lead Sponsor
- SOLTI Breast Cancer Research Group
- Brief Summary
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.
- Detailed Description
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.
Stratification factors will include number of previous regimens for advanced breast cancer (one and two vs three or more) and presence of visceral disease (yes vs no).
Treatment in all cohorts will be administered until progression, unacceptable toxicity, patient consent withdrawal, or death A total of 102 patients will be included. The inclusion period will be divided in two phases. During phase I it is planned to include 45 patients in 24 months; considering early stopping rule according to SF rate. During phase II, the trial will continue until the final evaluable number of 102 randomizations are included.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 73
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: HER2-positive/Hormone receptor-negative (Recruitment Closed) Palbociclib 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. Arm B2:HER+/HR+: trastuzumab + palbociclib +letrozole (Recruitment Closed) Endocrine therapy 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. Arm C1: Palbociclib, trastuzumab and endocrine therapy 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. Arm C2: Treatment based of physician's choice Endocrine therapy 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. Arm C2: Treatment based of physician's choice Chemotherapy 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. Arm C2: Treatment based of physician's choice Antibody-Drug Conjugates 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. Arm B1: HER2+/Hormone receptor-positive (Recruitment Closed) Palbociclib 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. Arm A: HER2-positive/Hormone receptor-negative (Recruitment Closed) Trastuzumab 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. Arm B1: HER2+/Hormone receptor-positive (Recruitment Closed) Trastuzumab 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. Arm B2:HER+/HR+: trastuzumab + palbociclib +letrozole (Recruitment Closed) Palbociclib 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. Arm C1: Palbociclib, trastuzumab and endocrine therapy Palbociclib 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. Arm B2:HER+/HR+: trastuzumab + palbociclib +letrozole (Recruitment Closed) Trastuzumab 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. Arm C1: Palbociclib, trastuzumab and endocrine therapy Trastuzumab 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. Arm C2: Treatment based of physician's choice Trastuzumab 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.
- Primary Outcome Measures
Name Time Method Progression-Free Survival at 6 months 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 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)
- Secondary Outcome Measures
Name Time Method Rate of Overall tumour objective response rate (ORR) in treatment arms (A and B). up to 5 years Number of patients who achieve complete or partial response according to RECIST 1.1 criteria during treatment.
Rate of Disease control rate (DCR) in treatment arms (A and B) up to 5 years Number of patients with objective response (complete or partial) or stable disease according to RECIST 1.1 criteria for at least 12 weeks.
Evaluation of time to progression (Cohorts A and B) up to 5 years Time between treatment start and disease progression
Cardiac Safety profile in arms A and B: Percentage of Participants with cardiac adverse events up to 5 years Frequency of cardiac events of any grade, frequency of grade III-IV grade cardiac events according to NYHA classification.
Overall Survival in treatment arms (Cohorts A and B). up to 5 years Measured as time between treatment start and all-cause death.
Rate of Disease control rate (DCR) in both treatment arms (C1 and C2) up to 4 years Number of patients with objective response (complete or partial) or stable disease according to RECIST 1.1 criteria for at least 8 weeks.
Rate of Overall tumour objective response rate (ORR) in treatment arms (C1 and C2). up to 4 years Number of patients who achieve complete or partial response according to RECIST 1.1 criteria during treatment.
Median duration of response in both treatment arms (C1 and C2). up to 4 years Time of median duration of response according to RECIST 1.1 by treatment arm.
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 The FACT-B consists of the Functional Assessment of Cancer Therapy-General (FACT-G) (27-items) and a breast-specific module: a 10-item instrument designed to assess patient concernsrelating to BC. The FACT-G is a 27-item compilation of general questions divided into 4 domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, and Functional Well-Being. Patients are asked to respond to a Likert scale where 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much.
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 The EuroQol EQ-5D is designed to assess health status in terms of a single index value or utility score. It contains 5 descriptors of current health state (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression) with each dimension having 5 levels of function (1=no problem, 2=slight problem, 3=moderate problem, 4=severe problem, and 5=unable/extreme). The scores on the 5 descriptors are summarized to create a single summary score. The EQ-5D also includes a visual analog scale (VAS), in which the patients self-rate their overall health status on a scale from 0 (worst imaginable) to 100 (best imaginable).
Safety profile in all treatment arms: Percentage of Participants with Adverse Events up to 5 years Measurements used to assess the safety profile will include adverse events of any grade, grade 3 and 4 adverse events, withdrawals due to adverse events and dose reductions due to adverse events. CTCAE v.5.0 will be used to evaluate AE grade.
To investigate biomarkers as predictors of response or resistance to the study treatment. up to 5 years Beyond PAM50 test, peripheral blood samples will be collected, and plasma extracted for circulating tumoral DNA (ctDNA) determination.
Trial Locations
- Locations (35)
ICO Hospitalet
🇪🇸Barcelona, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitario de Badajoz
🇪🇸Badajoz, Spain
Hospital Son Llatzer
🇪🇸palma de Mallorca, Spain
Hospital Álvaro Cunqueiro
🇪🇸Vigo, Spain
HU Clínico San Cecilio
🇪🇸Granada, Spain
Hospital Clínic de Barcelona
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital General Universitario de Valencia
🇪🇸Valencia, Spain
Complejo Hospitalario de Navarra
🇪🇸Pamplona, Spain
Hospital Virgen Universitario Virgen de Macarena
🇪🇸Sevilla, Spain
Hospital Quirón Salud Sagrado Corazón
🇪🇸Sevilla, Spain
Hospital General Universitario de Alicante
🇪🇸Alicante, Spain
Consorcio Hospitalario Provincial de Castellón
🇪🇸Castelló de la Plana, Spain
Hospital Universitario Sant Joan de Reus
🇪🇸Tarragona, Spain
H. U Puerta de Hierro
🇪🇸Madrid, Spain
Hospital Reina Sofía de Córdoba
🇪🇸Córdoba, Spain
H. Severo Ochoa
🇪🇸Madrid, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Instituto Valenciano de Oncología
🇪🇸Valencia, Spain
Hospital Universitario Virgen de las Nieves
🇪🇸Granada, Spain
Complejo Asistencial Universitario de León
🇪🇸León, Spain
HU Arnau de Vilanova Lleida
🇪🇸Lleida, Spain
Centro Integral Oncológico Clara Campal (CIOCC)
🇪🇸Madrid, Spain
Hospital Universitario Son Espases
🇪🇸palma de Mallorca, Spain
ICO-Badalona
🇪🇸Badalona, Barcelona, Spain
Hospital General De Catalunya
🇪🇸Sant Cugat Del Vallès, Barcelona, Spain
Complejo Hospitalario Universitario A Coruña
🇪🇸A Coruña, Spain
Hospital Universitario Rey Juan Carlos
🇪🇸Móstoles, Madrid, Spain
Hospital Universitario del Vall d' Hebron
🇪🇸Barcelona, Spain
Hospital de Basurto
🇪🇸Bilbao, Spain
Hospital San Pedro de Alcantara
🇪🇸Cáceres, Spain
Hospital Universitario Doce de Octubre
🇪🇸Madrid, Spain