Neoadjuvant Endocrine Therapy +/- the PI3K Inhibitor Inavolisib in HER2+, HR+, PIK3CA Mutant Early Breast Cancer
- Conditions
- HER2-positive Breast Cancer
- Interventions
- Registration Number
- NCT05306041
- Lead Sponsor
- German Breast Group
- Brief Summary
Evaluation of the potential incremental efficacy and safety of inavolisib in the neoadjuvant endocrine treatment of early-stage HER2-positive, HR-positive, PIK3CA mutant breast cancer.
- Detailed Description
This is a multicenter, prospective, randomized, open-label, parallel-group, phase II study to evaluate the potential incremental efficacy and safety of inavolisib in the neoadjuvant treatment of early-stage HER2-positive, HR-positive, PIK3CA mutant breast cancer.
170 patients with confirmed eligibility criteria and PIK3CA mutant breast cancer will be randomized in a 1:1 ratio to receive: Neoadjuvant endocrine therapy in combination with dual anti-HER2 blockade consisting of ready-to-use fixed-dose combination of pertuzumab and trastuzumab as subcutaneous (PH-FDC SC) formulation q3w for 6 cycles (18 weeks) with (6cycles) or without inavolisib. Endocrine therapy consists of either tamoxifen 20mg or an aromatase inhibitor +/- GnRH analogue for premenopausal women and men.
In both study arms, treatment will be given until surgery/core-biopsy, disease progression, unacceptable toxicity, or withdrawal of consent of the patient.
All patients will undergo surgery or biopsy after completing study therapy to assess pCR rate.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 170
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description without Inavolisib PHESGO Neoadjuvant endocrine therapy in combination with dual anti-HER2 blockade consisting of ready-to-use fixed-dose combination of pertuzumab and trastuzumab as subcutaneous (PH-FDC SC) formulation q3w for 6 cycles (18 weeks) Inavolisib PHESGO Inavolisib for 6 cycles (18 weeks) Neoadjuvant endocrine therapy in combination with dual anti-HER2 blockade consisting of ready-to-use fixed-dose combination of pertuzumab and trastuzumab as subcutaneous (PH-FDC SC) formulation q3w for 6 cycles (18 weeks) Inavolisib Endocrine therapy Inavolisib for 6 cycles (18 weeks) Neoadjuvant endocrine therapy in combination with dual anti-HER2 blockade consisting of ready-to-use fixed-dose combination of pertuzumab and trastuzumab as subcutaneous (PH-FDC SC) formulation q3w for 6 cycles (18 weeks) without Inavolisib Endocrine therapy Neoadjuvant endocrine therapy in combination with dual anti-HER2 blockade consisting of ready-to-use fixed-dose combination of pertuzumab and trastuzumab as subcutaneous (PH-FDC SC) formulation q3w for 6 cycles (18 weeks) Inavolisib Inavolisib Inavolisib for 6 cycles (18 weeks) Neoadjuvant endocrine therapy in combination with dual anti-HER2 blockade consisting of ready-to-use fixed-dose combination of pertuzumab and trastuzumab as subcutaneous (PH-FDC SC) formulation q3w for 6 cycles (18 weeks)
- Primary Outcome Measures
Name Time Method Pathologic complete response in the breast and axillary lymph nodes (ypT0/is ypN0) 21 weeks (time window + 3 weeks) Pathological complete response (ypT0/is ypN0) is defined as no microscopic evidence of residual invasive tumor cells in all resected specimens of the breast and axilla.
- Secondary Outcome Measures
Name Time Method Rates of ypT0 ypN0; ypT0 ypN0/+; ypT0/is ypN0/+; ypT(any) ypN0 21 weeks (time window + 3 weeks) ypT0 ypN0 is defined as no microscopic evidence of residual invasive or non-invasive viable tumor cells in all resected specimens of the breast and axilla; ypT0 ypN0/+ is defined as no microscopic evidence of residual invasive or non-invasive viable tumor cells in all resected specimens of the breast; ypT0/Tis ypN0/+ is defined as no microscopic evidence of residual invasive viable tumor cells in all resected specimens of the breast
pCR rates per arm separately for the stratified subpopulations 21 weeks (time window + 3 weeks) Pathological complete response (ypT0/is ypN0) is defined as no microscopic evidence of residual invasive tumor cells in all resected specimens of the breast and axilla.
Safety and tolerability profile (haematological and non-haematological adverse events) after the first 20 and the first 40 patients who started therapy and have completed two cycles of therapy 6 weeks Tolerability and safety analyses include assessment of patients whose treatment had to be dose reduced, delayed or permanently stopped. The reason for treatment discontinuation includes aspects of efficacy (e.g. discontinuation due to tumor progression), safety (e.g. discontinuation due to haematological and non-haematological adverse events) and compliance (e.g. discontinuation due to withdrawal of consent). Safety by toxicity grades are defined by the NCI-CTCAE version 5.0
Breast conservation rate after treatment 21 weeks (time window + 3 weeks) Breast conservation is defined as tumorectomy, segmentectomy or quadrantectomy as a most radical surgery.
Overall safety and tolerability and treatment compliance in the two arms 21 weeks (time window + 3 weeks) Descriptive statistics for the 2 treatment arms will be given on the number of patients whose treatment had to be dose reduced, delayed or permanently stopped. Reasons for premature discontinuation will be categorized according to the main reason and will be presented in frequency tables. Safety by toxicity grades are defined by the NCI-CTCAE version 5.0, laboratory parameters will be converted in CTC-grades and reported together with other adverse events.
Response rates of the breast tumor and axillary nodes based on physical examination and imaging tests (sonography, mammography, or MRI) after study treatment in both arms 21 weeks (time window + 3 weeks) Clinical (c) and imaging (i) response will be assessed every 2nd cycle and before surgery by physical examination and imaging tests. Sonography is the preferred examination.
The response categories of the breast are:
* Complete response (CR): complete disappearance of all tumor signs in the breast
* Partial response (PR): reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more
* Stable disease (NC): no significant change in tumor size during treatment which means an estimated reduction of the tumor area by less than 50%, or an estimated increase in the size of the tumor area lesions of less than 25%
* Progressive disease (PD): development of new, previously undetected lesions, or an estimated increase in the size of pre-existing lesions by 25% or more after at least two cycles of therapyPercentage of patients receiving additional neoadjuvant chemotherapy after residual disease was confirmed by core biopsy at the end of study treatment 21 weeks (time window + 3 weeks) In case of ycT0 and no tumor residuals in the biopsy, it is recommended to undergo surgery. Further neoadjuvant or adjuvant treatment including chemotherapy, radiotherapy, endocrine therapy and HER2-therapy will be administered at the discretion of the investigator and according to standard of care.
Invasive disease-free survival (IDFS) and overall survival (OS) in both arms and according to stratified subpopulations (data collected within a registry). up to 5 years Survival endpoints are defined as the time period between randomization and first event and will be analyzed after the end of the study by referring to data from GBG´s registries
Trial Locations
- Locations (29)
Hämatologie-Onkologie im Zentrum MVZ GmbH
🇩🇪Augsburg, Germany
DBZ Onkologie
🇩🇪Berlin, Germany
Praxisklinik Krebsheilkunde für Frauen
🇩🇪Berlin, Germany
Onkologische Schwerpunktpraxis Bielefeld
🇩🇪Bielefeld, Germany
Städtisches Klinikum Dessau
🇩🇪Dessau, Germany
University Hospital Carl Gustav Carus
🇩🇪Dresden, Germany
Center for Gynecologic Oncology
🇩🇪Düsseldorf, Germany
Frauenklinik des Universitätsklinikums Erlangen
🇩🇪Erlangen, Germany
Klinik für Gynäkologie und Geburtshilfe Agaplesion Markus Krankenhaus
🇩🇪Frankfurt, Germany
SRH Wald-Klinikum Gera GmbH
🇩🇪Gera, Germany
Mammazentrum HH am Krankenhaus Jerusalem
🇩🇪Hamburg, Germany
Klinikum Hanau
🇩🇪Hanau, Germany
DIAKOVERE Henriettenstift Frauenklinik
🇩🇪Hannover, Germany
National Center for Tumor Diseases - University Hospital Heidelberg
🇩🇪Heidelberg, Germany
Elisabeth Krankenhaus Brustzentrum
🇩🇪Kassel, Germany
Praxis für Hämatologie und Onkologie Koblenz and InVo - Institut für Versorgungsforschung in der Onkologie GbR
🇩🇪Koblenz, Germany
Department of Breast-Center Holweide - Kliniken der Stadt Köln
🇩🇪Köln, Germany
University Hospital Mannheim
🇩🇪Mannheim, Germany
University Hospital Gießen and Marburg, Campus Marburg
🇩🇪Marburg, Germany
Media Vita GmbH (MVZ)
🇩🇪Münster, Germany
University Hospital Tübingen
🇩🇪Tübingen, Germany
Department of Gynecology and Obstetrics - University of Ulm
🇩🇪Ulm, Germany
GRN Klinik Weinheim
🇩🇪Weinheim, Germany
Klinikum Worms
🇩🇪Worms, Germany
Helios Universitätsklinikum Wuppertal
🇩🇪Wuppertal, Germany
Università Politecnica delle Marche - Azienda Ospedaliero Universitarià delle Marche
🇮🇹Ancona, Italy
AULSS9 Scaligera - Ospedale Mater Salutis di Legnago
🇮🇹Legnago, Italy
Istituto Europeo di Oncologica
🇮🇹Milano, Italy
KEM Kliniken Essen-Mitte
🇩🇪Essen, NRW, Germany