Clinical trial NCT05063786: Trastuzumab + Alpelisib +/- Fulvestrant vs Trastuzumab + CT in Patients With PIK3CA Mutated Previously Treated HER2+ Advanced BrEasT Cancer (ALPHABET)
Official title: A Randomized Phase III Trial of Trastuzumab + ALpelisib +/- Fulvestrant Versus Trastuzumab + Chemotherapy in Patients With PIK3CA Mutated Previously Treated HER2+ Advanced BrEasT Cancer. "ALPHABET Study".
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Advanced Breast Cancer
Keywords: Alpelisib
Metastatic Breast Cancer
PIK3CA mutated
HER2 positive
Lead sponsor: Spanish Breast Cancer Research Group
Sponsor class: OTHER
Collaborators: name: ETOP IBCSG Partners Foundation
name: Breast International Group
name: Novartis Pharmaceuticals
First posted: 2021-10-01
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Randomized phase III trial of trastuzumab + Alpelisib +/- fulvestrant versus trastuzumab + chemotherapy in patients with PIK3CA mutated previously treated HER2+ Advanced Breast cancer.

Detailed description: This is an international, multicenter, open-label, controlled phase III randomized clinical trial in HER2+ advanced breast cancer (ABC) patients harboring PIK3CA mutation.

Approximately 300 patients (144 in the Hormone Receptor (HR)- cohort and 156 in the HR+ cohort) will be enrolled.

Central screening of PIK3CA mutations on the most recent available formalin-fixed paraffinembedded (FFPE) tumor sample is required for the purpose of eligibility. Investigators will be encouraged to send the most recent tumor tissue, preferably from a metastatic lesion. However, if this is not possible, archived tissue samples either from primary tumor or metastatic lesion will be acceptable. Local screening of HR and HER2 status is required (although there will be a central confirmation done retrospectively).

Once the screening process (locally at each site and at the central laboratory) is completed, fully eligible patients will be randomized in a 1:1 fashion to the control arm with trastuzumab plus chemotherapy (CT) or to the experimental arm with trastuzumab + alpelisib +/- fulvestrant (depending on HR status). The two patient cohorts defined according to HR status will be randomized separately, with randomization in each cohort stratified by prior treatment with pertuzumab (yes vs no) and number of prior anti-HER2 based therapy lines for MBC (≤2 vs \>2).

In both cohorts patients will continue to receive their assigned treatment until objective disease progression, symptomatic deterioration, unacceptable toxicity, death, or withdrawal of consent, whichever occurs first.

After objective disease progression, patients in both treatment arms will be followed until death or withdrawal of consent.

In order to perform exploratory biomarker analysis, pre-treatment tumor and sequential blood samples (at baseline, at week 9, at the end of treatment (EOT), and at progressive disease (PD)) will be obtained. Additionally, blood samples from approximately 100 patients (50 HR+ and 50 HR-) screened and without PIK3CA mutation will be collected.

Eligibility criteria: Inclusion Criteria:

Patients are eligible to be enrolled for randomization in the study only if they meet all of the following criteria:

1. Written informed consent prior to any specific study procedures, showing patient willingness to comply with all study procedures.
2. Histologically or cytologically documented locally recurrent inoperable or metastatic breast cancer with HER2+ status based on local laboratory determination, preferably on the most recent available FFPE tumor sample, and according to American Society of ClinicalOncology (ASCO)/College of American Pathologists (CAP) international guidelines valid at the time of the assay. In case of discordance in HER2+ status in different biopsies, we will consider the result from the most recent biopsy one will be used.
3. Documented HR status based on local laboratory, preferably on the most recent available FFPE tumor sample, and according to ASCO/CAP international guidelines valid at the time of the assay. In case of discordance in HR status in different biopsies, the result from the most recent biopsy will be used. HR+ will be defined as ≥1% positive cells by immunohistochemistry for Estrogen Receptor (ER) and/or Progesterone Receptor (PgR). HR- will be defined as \<1% positive cells by immunohistochemistry for both ER and PgR. Considering that there are limited data on endocrine therapy benefit for cancers with 1% to 10% of cells staining ER positive, for the purpose of this study, patients with ER and PgR expression between 1 and 10% (considered to be HR low by the most recent ASCO/CAP guidelines) will be eligible for inclusion in the HR- cohort.
4. Patients with a PIK3CA tumor mutation at central laboratory determination, preferably on the most recent available FFPE tumor sample.
5. At least 1 but no more than 5 prior lines of anti-HER2 based therapy for metastatic breast cancer (MBC). Maintenance therapy will not count as an additional line of therapy.
6. At least 1 prior line of trastuzumab in the metastatic setting, or in the (neo)adjuvant setting (provided the patient relapsed while on therapy or within 6 months after completing adjuvant trastuzumab).
7. Female or male patient is at least 18 years of age.
8. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
9. Patients can be either males or premenopausal/perimenopausal or postmenopausal females. In the HR+ cohort, males and females who are not post-menopausal must have been on a gonadotropin-releasing hormone (GnRH) agonist (e.g. goserelin or leuprorelin) for at least 28 days prior to starting study treatment.

   Premenopausal status is defined as either:
   * Last menstrual period occurred within the last 12 months, or
   * If on tamoxifen: last menstrual period occurred within the past 14 days, plasma estradiol is ≥ 10 pg/mL and follicle-stimulating hormone (FSH) ≤ 40 IU/l or in the premenopausal range, according to local laboratory definition, or
   * In case of therapy induced amenorrhea: plasma estradiol is ≥ 10 pg/mL and FSH ≤ 40 IU/l or in the premenopausal range, according to local laboratory definition.

   Postmenopausal status is defined as either:

   - Natural (spontaneous) amenorrhea lasting more than 12 months and either age from49 to 59 years and/or history of vasomotor symptoms (e.g., hot flush) in the absence of other medical justification, or Levels of plasma estradiol ≤ 20 pg/mL and follicle-stimulating hormone (FSH) ≥ 40 IU/l or in the postmenopausal range, according to local laboratory definition, or Surgical bilateral oophorectomy.

   Perimenopausal status is defined as neither premenopausal nor postmenopausal.
10. Measurable disease or at least one evaluable bone lesion, lytic or mixed (lytic+blastic), which has not been previously irradiated and is assessable by computer tomography (CT)/magnetic resonance imaging (MRI) in the absence of measurable disease according to RECIST 1.1 criteria.
11. Life expectancy ≥ 12 weeks.
12. Adequate organ and marrow function defined as follows:

    * Absolute neutrophil count (ANC) ≥ 1,500/mm3 (1.5x109/L).
    * Platelets ≥ 100,000/mm3 (100x109/L).
    * Hemoglobin ≥ 9g/dL (90g/L).
    * Calcium (corrected for serum albumin) and magnesium within normal limits or ≤ grade 1 according to NCI-CTCAE version 5.0 if judged clinically not significant by the investigator.
    * Creatinine \<1.5 x upper limit of normal (ULN) or creatinine Clearance ≥ 35 mL/min using Cockcroft-Gault formula (if creatinine is ≥1.5 ULN).
    * Total bilirubin \< 2 x ULN (any elevated bilirubin should be asymptomatic at enrollment) except for patients with Gilbert's syndrome who may only be included if the total bilirubin is ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN.
    * Potassium within normal limits, or corrected with supplements.
    * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN.

    If patient has liver metastasis, AST and ALT ≤ 5.0 x ULN (elevated AST or AST values must be stable for 2 weeks, without evidence of biliary obstruction by imaging).
    * Fasting serum amylase ≤ 2.0 x ULN.
    * Fasting serum lipase ≤ ULN.
    * Fasting plasma glucose (FPG) \< 140 mg/dL (7.7 mmol/L) and glycosylated hemoglobin (HbA1c) \< 6.5%.
13. Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI-CTCAE version 5.0 grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator´s discretion).
14. Adequate cardiac function as defined by left ventricular ejection fraction (LVEF) of ≥ 50% measured by echocardiography or multi-gated acquisition (MUGA) scans.

Exclusion Criteria:

Patients will be excluded from the study if they meet any of the following criteria:

1. Have received more than 5 previous lines of anti-HER2 based therapy for MBC, or prior fulvestrant.
2. Symptomatic visceral disease or any disease burden that makes the patient ineligible for experimental therapy per the investigator's best judgment.
3. Symptomatic central nervous system (CNS) metastases. However, patients with CNS metastases who have been adequately treated, are asymptomatic and do not require corticosteroid or anti-epileptic medication are eligible.
4. Presence of leptomeningeal carcinomatosis.
5. Other invasive malignancy (different from the current breast cancer) at the time of enrollment or previous diagnosis of a completely removed malignancy within 3 years prior to randomization except for adequately treated (including complete surgical removal) of International Federation of Gynecology and Obstetrics (FIGO) stage I grade 1 endometrial cancer, basal or squamous cell carcinoma of the skin, thyroid cancer limited to thyroid gland, in situ carcinoma of the cervix, and grade 1-2 early stage bladder cancer defined as T1 or less, without nodal involvement (N0).
6. Patients with an established diagnosis of diabetes mellitus type I or not controlled type II (FPG ≥ 140 mg/dL \[7.7 mmol/L\] or HbA1c ≥ 6.5%), or history of gestational diabetes (as per American College of Obstetricians and Gynecologists (ACOG) guidelines) or documented steroid-induced diabetes mellitus.
7. Prior treatment with any mTOR, AKT or PI3K inhibitor.
8. Patients treated within the last 7 days prior to treatment initiation with:

   * Drugs that are strong inducers of CYP3A4.
   * Drugs that are inhibitors of Breast Cancer Resistance Protein (BCRP).
9. Patients who received before randomization:

   * Any investigational agent within 4 weeks.
   * Chemotherapy within a period of time that is shorter than the cycle duration used for that treatment (e.g. \< 3 weeks for fluorouracil, doxorubicine, epirubicin or \< 1 week for weekly chemotherapy).
   * Biologic therapy (e.g., antibodies, other than trastuzumab which is permitted): within 4 weeks prior to starting study treatment.
   * Endocrine therapy: tamoxifen or aromatase inhibitor (AI) within 2 weeks prior to starting study treatment.
   * Corticosteroids within 2 weeks prior to starting study treatment. Note: the following uses of corticosteroids are permitted at any time: single doses, topical applications(e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular).
   * Radiotherapy within 2 weeks prior to starting study treatment (all acute toxic effects must be resolved to NCI-CTCAE version 5.0 grade \<1, except toxicities not considered a safety risk for the patient at investigator´s discretion). Patients who received prior radiotherapy to \>25% of bone marrow are not eligible regardless of when it was administered.
   * Major surgery or other anti-cancer therapy not previously specified within 4 weeks prior to starting study treatment, (all acute toxic effects, including peripheral neurotoxicity must be resolved to NCI-CTCAE version 5.0 grade ≤ 1, except toxicities not considered a safety risk for the patient at the investigator´s discretion).
10. Patient has clinically significant, uncontrolled heart disease and/or recent cardiac events including any of the following:

    * History of angina pectoris, coronary artery bypass graft (CABG), symptomatic pericarditis or myocardial infarction within 6 months of randomization.
    * History of documented congestive heart failure (New York Heart Association functional classification III-IV).
    * Clinically significant cardiac arrhythmias, (e.g., ventricular tachycardia), complete left bundle branch block, high grade AV block (e.g. bifascicular block, Mobitz type II and third degree AV block without pacemaker in place).
    * Uncontrolled hypertension defined by a Systolic Blood Pressure ≥ 160 mmHg and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, with or without anti-hypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening.
    * Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or Fridericia QT correction formula (QTcF) \> 470msec.
    * Bradycardia (heart rate \< 50 at rest), by electrocardiogram (ECG) or pulse.
    * Inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF \> 460 msec for females (using Fridericia's correction). All as determined by screening ECG.
11. Bleeding diathesis (i.e., Disseminated Intravascular Coagulation (DIC), clotting factor deficiency) or long-term (\> 6 months) anticoagulant therapy, other than antiplatelet therapy and low dose coumarin derivatives, provided that the International Normalised Ratio (INR) is less than 1.5.
12. History of clinically significant bowel disease including abdominal fistula, or gastrointestinal perforation.
13. Difficulties to swallow tablets, malabsorption syndrome disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, or active inflammatory bowel disease (e.g., ulcerative diseases).
14. Known hypersensitivity to trastuzumab, alpelisib or fulvestrant or any of their excipients. If known hypersensitivity to either vinorelbine, capecitabine, eribulin or any of their excipients, patient will be eligible as long as the investigator's choice avoids that drug in the control arm.

    If known hypersensitivity to all three cytostatics (vinorelbine, capecitabine and eribulin), the patient will not be eligible.
15. Known positive serology for Human Immunodeficiency Virus (HIV), or active infection for hepatitis B or hepatitis C.
16. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
17. Patients with currently documented pneumonitis/interstitial lung disease (the chest Computed Tomography \[CT\] scan performed at screening for the purpose of tumor assessment should be reviewed to confirm that there are no relevant pulmonary complications present).
18. Patient with liver disease with a Child Pugh score B or C.
19. Patient with a history of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis.
20. Patient has a history of Steven-Johnson-Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN).
21. Patient is nursing (lactating) or is pregnant as confirmed by a positive serum human Chorionic Gonadotropin (hCG) test prior to initiating study treatment.
22. Patient is a woman of child-bearing potential or a partner of a woman of child-bearing potential, unless agreement to remain abstinent or use single or combined non-hormonal contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 7 months after the last dose of study treatment, except for patients receiving fulvestrant in which this period should be of at least 2 years.

    * Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient.
    * Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.
    * Examples of non-hormonal contraceptive methods with a failure rate of \< 1% per year include tubal ligation, male sterilization (only if he is the sole partner and have been performed at least 6 months prior to screening), and certain intrauterine devices.
    * Alternatively, two methods (e.g., two barrier methods such as a condom and a cervical cap) may be combined to achieve a failure rate of \< 1% per year. Barrier methods must always be supplemented with the use of a spermicide.
    * Male participants must not donate sperm during study and up to the time period specified above.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: The accumulation of targeted PFS events is estimated at 44 and 38 months since first patients randomized, in the HR- and HR+ cohorts, respectively.
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Approximately 59 months from the inclusion of the first patient.
measure: Objective Response (OR)
timeFrame: Through study completion, an average of 59 months from the inclusion of the first patient.
measure: Safety and tolerability
timeFrame: During the study treatment period or within 30 days of the last dose of study treatment.
Other outcomes:
measure: Time to first subsequent therapy (TFST)
timeFrame: After disease progression or unacceptable toxicity up approximately 59 months from the inclusion of the first patient.
measure: Time to first subsequent therapy cessation (TFSTC)
timeFrame: At the finalization of the first subsequent line of systemic therapy after study treatment estimated to be approximately 59 months from the inclusion of the first patient.
measure: Change in the National Comprehensive Cancer Network - Functional- Breast Cancer Symptom Index-16 (NFBSI) summary score from baseline to 9 weeks after randomization
timeFrame: Baseline and 9 weeks after randomization.
measure: Time to deterioration (TTD) in QoL.
timeFrame: QoL will be assessed at baseline;every 3 weeks until week 9 and then every 6 weeks until progression and at the post-treatment visit.
measure: PIK3CA mutations determined in tumor and blood samples, and their correlation with efficacy variables.
timeFrame: At baseline, at week 9, at the end of treatment [EOT] and at Progression Disease estimated up to 9 months.
Locations:
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck - Univ.Klinik f. Frauenheilkunde Innsbruck
city: Leoben
country: Austria
facility: LKH Hochsteiermark - Leoben
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH - BHS
city: Pölten
country: Austria
facility: Universitätsklinikum St. Pölten
city: Steyr
country: Austria
facility: Pyhrn - Eisenwurzen Klinikum Steyr
city: Wien
country: Austria
facility: Klinik Hietzing Wien
city: Wien
country: Austria
facility: Klinik Ottakring
city: Wien
country: Austria
facility: Medizinische Universität Wien - Univ.klinikum AKH Wien
city: Chambray-lès-Tours
country: France
facility: Centre d'Oncologie et Radiothérapie 37
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Dijon
country: France
facility: Centre Régional De Lutte Contre Le Cancer Georges-François Leclerc
city: Limoges
country: France
facility: Centre hospitalier universitaire à Limoges
city: Paris
country: France
facility: Institut Curie Hospital
city: Poitiers
country: France
facility: Centre hospitalier universitaire de Poitiers
city: Saint-Cloud
country: France
facility: Institute Curie - Site Saint-Cloud
city: Alessandria
country: Italy
facility: A.O. "SS Antonio e Biagio e Cesare Arrigo"
city: Ancona
country: Italy
facility: Clinica Oncologica, AOU Riuniti
city: Bolzano
country: Italy
facility: Ospedale di Bolzano Azienda Sanitaria Alto Adige
city: Castellanza
country: Italy
facility: Ospedale MultiMedica Castellanza
city: Catania
country: Italy
facility: Cannizzaro Hospital
city: Cremona
country: Italy
facility: ASST Cremona
city: Florence
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi, University of Florence
city: Genoa
country: Italy
facility: IRCCS Policlinico San Martino
city: Legnago
country: Italy
facility: Mater Salutis Hospital
city: Mantova
country: Italy
facility: ASST-Mantova- Hospital Carlo Poma
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei tumori
city: Milano
country: Italy
facility: IEO - Istituto Europeo di Oncologia
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Monselice
country: Italy
facility: Ospedali Riuniti Monselice Padova
city: Novara
country: Italy
facility: AOU Maggiore della Caritá
city: Palermo
country: Italy
facility: Casa di Cura La Maddalena S.P.A.
city: Parma
country: Italy
facility: Azienda Ospedaliero-Universitaria di Parma
city: Pavia
country: Italy
facility: Istituti Clinici Scientifici Maugeri SpA-SB
city: Rimini
country: Italy
facility: AUSL Romagna/Oncology Department
city: Roma
country: Italy
facility: Istituti Fisioterapici ospitaliersi - IFO - Istituti Regina Elena
city: Roma
country: Italy
facility: Policlinico Umberto I
city: Sassuolo
country: Italy
facility: UOSD AUSL Modena
city: Trento
country: Italy
facility: Santa Chiara Hospital
city: Turin
country: Italy
facility: Sant'Anna Hospital - Città della salute e della scienza
city: Udine
country: Italy
facility: Department of Oncology, ASUFC, PO Sm Misericordia
city: Nijmegen
country: Netherlands
facility: Radboud Medical Center
state: Güeldres
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
city: Den Haag
country: Netherlands
facility: HagaZiekenhuis
city: Goes
country: Netherlands
facility: Adrz Medisch Centrum
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis
city: Maastricht
country: Netherlands
facility: Maastricht UMC
city: Terneuzen
country: Netherlands
facility: ZorgSaam Ziekenhuis
city: Utrecht
country: Netherlands
facility: Diakonessenhuis Utrecht
city: Venlo
country: Netherlands
facility: VieCuri Medisch Centrum
city: A Coruña
country: Spain
facility: Centro Oncoloxico de Galicia
city: A Coruña
country: Spain
facility: Complexo Hospitalario Universitario A Coruña
city: A Coruña
country: Spain
facility: Hospital Clínico Universitario de Santiago CHUS
city: Albacete
country: Spain
facility: Complejo Hospitalario Universitario de Albacete
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Badajoz
country: Spain
facility: Hospital Universitario de Badajoz
city: Badalona
country: Spain
facility: ICO Badalona - Hospital Universitario Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Bilbao
country: Spain
facility: Hospital Universitario Basurto
city: Bilbao
country: Spain
facility: Hospital Galdakao-Usansolo
city: Bilbao
country: Spain
facility: Hospital Universitario de Cruces
city: Cadiz
country: Spain
facility: Hospital Universitario Puerta del Mar
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcántara
city: Donostia
country: Spain
facility: Hospital Universitario Donostia
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
city: Girona
country: Spain
facility: ICO de Girona - Hospital Josep Trueta
city: Granada
country: Spain
facility: Hospital Universitario Clínico San Cecilio
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Huelva
country: Spain
facility: Hospital Universitario Juan Ramón Jiménez
city: Jaén
country: Spain
facility: Hospital Universitario de Jaen
city: Jerez De La Frontera
country: Spain
facility: Hospital Universitario de Jerez de la Frontera
city: Lleida
country: Spain
facility: Hospital Universitario Arnau de Vilanova de Lleida
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario de Fuenlabrada
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro - CIOCC Clara Campal
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Madrid
country: Spain
facility: Hospital Universitario Ramon Y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Severo Ochoa
city: Manresa
country: Spain
facility: Althaia Xarxa Assistencial de Manresa
city: Mataró
country: Spain
facility: Hospital de Mataró
city: Murcia
country: Spain
facility: Hospital Clinico Universitario Virgen de La Arrixaca
city: Málaga
country: Spain
facility: Hospital Universitario Regional de Malaga
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Espases
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Llatzer
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
city: Sabadell
country: Spain
facility: Corporació Sanitaria Parc Taulí
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de Valme
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Tarragona
country: Spain
facility: Hospital Universitario Sant Joan de Reus
city: Tenerife
country: Spain
facility: Hospital Universitario de Canarias
city: Tenerife
country: Spain
facility: Hospital Universitario Nuestra Señora de la Candelaria
city: Terrassa
country: Spain
facility: Hospital de Terrassa - Consorci Sanitari de Terrassa
city: Toledo
country: Spain
facility: Hospital Virgen de la Salud
city: Valencia
country: Spain
facility: Consorcio Hospital General Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario Arnau de Vilanova de Valencia
city: Zamora
country: Spain
facility: Hospital Provincial de Zamora (Complejo Asistencial de Zamora)
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Aarau
country: Switzerland
facility: Tumor Zentrum Aarau
city: Berne
country: Switzerland
facility: Inselspital, Universitätsspital Bern
city: Fribourg
country: Switzerland
facility: Centre du sein Fribourg
Study officials:
affiliation: H. Clínico Universitario Valencia. Valencia, Spain.
name: Study Director
role: STUDY_DIRECTOR
affiliation: Istituto Europeo di Oncologia. Milan, Italy.
name: Study Director
role: STUDY_DIRECTOR
affiliation: Princess Margaret Cancer Center. Toronto, Canada
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Perez-Fidalgo JA, Criscitiello C, Carrasco E, Regan MM, Di Leo A, Ribi K, Adam V, Bedard PL. A phase III trial of alpelisib + trastuzumab +/- fulvestrant versus trastuzumab + chemotherapy in HER2+ PIK3CA-mutated breast cancer. Future Oncol. 2022 Jun;18(19):2339-2349. doi: 10.2217/fon-2022-0045. Epub 2022 Apr 25.