Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   42158   clinical trials with a EudraCT protocol, of which   6934   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2019-002455-42
    Sponsor's Protocol Code Number:WO41554
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-01-25
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2019-002455-42
    A.3Full title of the trial
    A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY EVALUATING THE EFFICACY AND SAFETY OF GDC-0077 PLUS PALBOCICLIB AND FULVESTRANT VERSUS PLACEBO PLUS PALBOCICLIB AND FULVESTRANT IN PATIENTS WITH PIK3CA-MUTANT, HORMONE RECEPTOR POSITIVE, HER2-NEGATIVE LOCALLY ADVANCED OR METASTATIC BREAST CANCER
    STUDIO DI FASE III RANDOMIZZATO, IN DOPPIO CIECO, CONTROLLATO CON PLACEBO, VOLTO A VALUTARE EFFICACIA E SICUREZZA DI GDC 0077 PIÙ PALBOCICLIB E FULVESTRANT VS. PLACEBO PIÙ PALBOCICLIB E FULVESTRANT IN PAZIENTI CON CARCINOMA MAMMARIO METASTATICO LOCALMENTE AVANZATO O METASTATICO, POSITIVO AI RECETTORI ORMONALI, HER2-NEGATIVO E CON MUTAZIONE DI PIK3CA
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study Evaluating the Efficacy and Safety of GDC-0077 Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Patients with PIK3CA-Mutant, Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer.
    Studio volto a valutare l’efficacia e la sicurezza di GDC-0077 in associazione a Palbociclib e Fulvestrant rispetto a placebo in associazione a a Palbociclib e Fulvestrant in pazienti affetti da Carcinoma mammario localmente avanzato o metastatico, con mutazione di PIK3CA, positivo ai recettori ormonali ed HER2-Negativo.
    A.3.2Name or abbreviated title of the trial where available
    -
    -
    A.4.1Sponsor's protocol code numberWO41554
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorF. HOFFMANN - LA ROCHE LTD.
    B.1.3.4CountrySwitzerland
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportF. Hoffmann-La Roche Ltd
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationF. Hoffmann-La Roche Ltd
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasilea
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number000000
    B.5.5Fax number000000
    B.5.6E-mailglobal.rochegenentechtrials@roche.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameGDC-0077
    D.3.2Product code [RO711-3755/F08-02]
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeRO7113755
    D.3.9.3Other descriptive nameGDC-0077
    D.3.9.4EV Substance CodeSUB184338
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number9
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name IBRANCE
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Inc. US - AIC: 0069-0188-21
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePalbociclib
    D.3.2Product code [RO4991855]
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPALBOCICLIB
    D.3.9.1CAS number 571190-30-2
    D.3.9.2Current sponsor codeRO4991855
    D.3.9.3Other descriptive nameIbrance
    D.3.9.4EV Substance CodeSUB177204
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameGDC-0077
    D.3.2Product code [RO711-3755/F09-02]
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeRO7113755
    D.3.9.3Other descriptive nameGDC-0077
    D.3.9.4EV Substance CodeSUB184338
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number3
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Faslodex
    D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca - EU/1/03/269/002
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameFaslodex (Fulvestrant)
    D.3.2Product code [RO3208209]
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntramuscular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNFULVESTRANT
    D.3.9.2Current sponsor code-
    D.3.9.3Other descriptive nameFaslodex
    D.3.9.4EV Substance CodeSUB13933MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 5
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name IBRANCE
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Inc. US - AIC: 0069-0187-21
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePalbociclib
    D.3.2Product code [RO4991855]
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPALBOCICLIB
    D.3.9.1CAS number 571190-30-2
    D.3.9.2Current sponsor codeRO4991855
    D.3.9.3Other descriptive nameIbrance
    D.3.9.4EV Substance CodeSUB177204
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 6
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name IBRANCE
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Inc. US - AIC: 0069-0189-21
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePalbociclib
    D.3.2Product code [RO4991855]
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPALBOCICLIB
    D.3.9.1CAS number 571190-30-2
    D.3.9.2Current sponsor codeRO4991855
    D.3.9.3Other descriptive nameIbrance
    D.3.9.4EV Substance CodeSUB177204
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number125
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Breast cancer
    Carcinoma mammario
    E.1.1.1Medical condition in easily understood language
    Breast cancer is a cancer that develops in the tissues of the breast.
    Il carcinoma mammario è un tumore che si sviluppa nei tessuti della mammella.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10027475
    E.1.2Term Metastatic breast cancer
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of GDC-0077 plus palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant on the basis of progression-free survival
    Valutare l’efficacia di GDC 0077 in associazione a palbociclib e fulvestrant rispetto a placebo più palbociclib e fulvestrant sulla base della sopravvivenza libera da progressione (PFS)
    E.2.2Secondary objectives of the trial
    •To evaluate the efficacy of GDC-0077 plus palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant on the basis of objective response rate; best overall response rate; duration of response; clinical benefit rate; overall survival; and times to deterioration in pain, physical function, role function, and global health status (GHS)/health-related quality of life (HRQoL)
    •To evaluate the safety of GDC-0077 plus palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant on basis of incidence and severity of adverse events, change from baseline in targeted vital signs, clinical laboratory test results, and electrocardiogram (ECG) parameters
    •To characterize the pharmacokinetics of GDC-0077, palbociclib, and fulvestrant, when administered in combination in this population on the basis of their plasma concentrations at specified timepoints
    •Valut. l’efficacia di GDC 0077 in associazione a palbociclib e fulvestrant rispetto a placebo più palbociclib e fulvestrant sulla base di tasso di risposta obiettiva (ORR); miglior tasso di risposta complessivo (BOR); durata della risposta (DOR); tasso di beneficio clinico (CBR); sopravvivenza globale (OS); e tempo al peggioramento (TTD) del dolore, della funzione fisica, delle funzioni di ruolo, e dello stato di salute generale (GHS)/della qualità di vita correlata alla salute (HRQoL)
    •Valut.la sicurezza di GDC 0077 più palbociclib e fulvestrant rispetto a placebo più palbociclib e fulvestrant sulla base di incidenza e gravità degli eventi avversi, variazione dal basale di parametri vitali mirati, risultati di analisi cliniche di laboratorio mirate, e parametri ECG
    •Caratterizz. la farmacocinetica di GDC 0077, palbociclib e fulvestrant, quando somministrati in associazione in questa popolaz., sulla base della loro concentrazione plasmatica in specifici momenti di rilevazione
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Signed Informed Consent Form
    - Women or men ¿ 18 years of age at time of signing Informed Consent Form
    - If female, patients must meet at least one of the following definitions:
    Postmenopausal, as defined by at least one of the following criteria:
    – Age 60 years
    – Age 60 years and 12 months of amenorrhea plus follicle-stimulating hormone and plasma estradiol levels within postmenopausal range by local laboratory assessment in the absence of oral contraceptive pills, hormone replacement therapy, or gonadotropin-releasing hormone agonist or
    antagonist
    – Documented bilateral oophorectomy (14 days prior to first treatment on
    Day 1 of Cycle 1 and recovery to baseline)
    Premenopausal or perimenopausal (i.e., not meeting the criteria for postmenopausal) and meeting the following criterion:
    – Treatment with luteinizing hormone¿releasing hormone (LHRH) agonist therapy (e.g., goserelin or leuprolide) beginning at least 2 weeks prior to Day 1 of Cycle 1 and continuing for the duration of study treatment
    If male, recommendation of treatment with LHRH agonist therapy (e.g., goserelin or leuprolide) beginning at least 2 weeks prior to Day 1 of Cycle 1 and continuing for the duration of study treatment
    -Histologically or cytologically confirmed adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to surgical or radiation therapy with curative intent - Documented ER-positive and/or progesterone receptor¿positive tumor according to American Society of Clinical Oncology/College of American Pathologists
    (ASCO/CAP) guidelines, defined as ¿ 1% of tumor cells stained positive based on
    the most recent tumor biopsy and assessed locally
    - Documented HER2-negative tumor according to ASCO/CAP guidelines, defined as a HER2 immunohistochemistry (IHC) score of 0 or 1¿, or an IHC score of 2¿ accompanied by a negative fluorescence, chromogenic, or silver in situ hybridization
    test indicating the absence of HER2 gene amplification, or a HER2/CEP17 ratio of 2.0 based on the most recent tumor biopsy and assessed locally
    - Confirmation of biomarker eligibility: valid results from either central testing of blood
    or local testing of blood or tumor tissue documenting PIK3CA-mutant tumor status
    -Consent to provide fresh (preferred) or archival tumor tissue specimen. It is preferred that the specimen be from the most recently collected and available tumor tissue, and whenever possible, from a metastatic site of disease. See the laboratory manual for specimen requirements.
    - Patients must have progressed during adjuvant endocrine treatment or within 12 months of completing adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen
    - Measurable disease per RECIST v1.1
    • Firma del modulo di consenso informato
    • Donne o uomini di età ¿ 18 anni al momento della firma del modulo di consenso informato
    • Le pazienti di sesso femminile devono presentare almeno una delle seguenti caratteristiche:
    Stato di postmenopausa, dimostrato dalla presenza di almeno uno dei seguenti criteri:
    Età maggiore o uguale a 60 anni
    Età minore di 60 anni e 12 mesi di amenorrea con livelli plasmatici di ormone follicolo-stimolante ed estradiolo che ricadono nel range postmenopausale in base alla valutazione di un laboratorio locale, in assenza di pillola contraccettiva, terapia ormonale sostitutiva o agonisti o antagonisti dell’ormone di rilascio delle gonadotropine
    Ovariectomia bilaterale documentata (¿ 14 giorni prima del primo trattamento il Giorno 1 del Ciclo 1 e ripristino delle condizioni basali)
    Stato di premenopausa o perimenopausa (ossia, mancato soddisfacimento dei criteri di postmenopausa) e soddisfacimento del seguente criterio:
    Trattamento con agonisti dell’ormone di rilascio dell’ormone luteinizzante (LHRH) (per es., goserelin o leuprolide) iniziato almeno 2 settimane prima del Giorno 1 del Ciclo 1 e destinato a proseguire per l’intera durata del trattamento dello studio
    Per i pazienti di sesso maschile si raccomanda la terapia con agonisti dell’LHRH (per es., goserelin o leuprolide) da iniziare almeno 2 settimane prima del Giorno 1 del Ciclo 1 e da proseguire per l’intera durata del trattamento dello studio
    • Adenocarcinoma mammario istologicamente o citologicamente confermato, che sia localmente avanzato o metastatico e non soggetta a resezione chirurgica o terapia locale con intento curativo
    • Tumore con positività documentata per il recettore degli estrogeni (ER) e/o il recettore progestinico ai sensi delle linee guida dell’American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP), definito dalla presenza di ¿ 1% di cellule tumorali con colorazione positiva alla più recente biopsia del tumore valutata localmente
    • Tumore con negatività documentata di HER2 ai sensi delle linee guida ASCO/CAP, definito da un punteggio dell’esame immunoistochimico (IHC) per HER2 di 0 o 1¿, oppure da un punteggio IHC di 2¿ associato a un test di ibridazione in situ in fluorescenza, cromogenica o ad argento indicante l’assenza di amplificazione del gene HER2, oppure un rapporto HER2/CEP17 di ¿ 2,0 in base alla più recente biopsia del tumore valutata localmente
    • Conferma dell’eleggibilità per i biomarcatori: risultati validi di un’analisi centrale sul sangue o un’analisi locale su sangue o tessuto tumorale che documentino lo stato mutazionale di PIK3CA nel tumore
    • Consenso a fornire un campione di tessuto tumorale fresco (da preferire) o d’archivio. Il campione deve preferibilmente provenire dal tessuto tumorale disponibile prelevato più recentemente e, dove possibile, da un sito di malattia metastatica. Per i requisiti sui campioni si rimanda al manuale di laboratorio.
    • I pazienti devono essere andati incontro a una progressione della malattia durante la terapia endocrina adiuvante o nei 12 mesi successivi al completamento della terapia endocrina adiuvante con un inibitore dell’aromatasi o con tamoxifene
    Se è stato incluso un inibitore CDK4/6 come parte della terapia neoadiuvante o adiuvante, l'evento di progressione deve avvenire > 12 mesi dal completamento della porzione con inibitore CDK4/6 della terapia neoadiuvante o adiuvante.
    • Malattia misurabile secondo i criteri RECIST v 1.1
    E.4Principal exclusion criteria
    - Metaplastic breast cancer
    -Any history of leptomeningeal disease or carcinomatous meningitis
    -Any prior systemic therapy for metastatic breast cancer
    Prior treatment with fulvestrant or any selective estrogen-receptor degrader
    - Prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose
    mechanism of action is to inhibit the PI3K-AKT-mTOR pathway
    - Appropriate for treatment with cytotoxic chemotherapy at time of entry into the
    study, as per national or local treatment guidelines (e.g., patients with visceral crisis)
    - Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or
    any history of Type 1 diabetes
    - Inability or unwillingness to swallow pills or receive intramuscular injections
    - Malabsorption syndrome or other condition that would interfere with
    enteral absorption
    - Known and untreated, or active CNS metastases
    - Clinically significant and active liver disease, including severe liver impairment (Child-Pugh Class B/C), viral or other hepatitis, current alcohol abuse, or cirrhosis
    • Carcinoma mammario metaplastico
    • Anamnesi di malattia leptomeningea o meningite carcinomatosa
    • Qualsiasi precedente terapia sistemica per il carcinoma mammario metastatico
    • Precedente trattamento con fulvestrant o qualsiasi trattamento che degrada selettivamente i recettori per gli estrogeni
    • Precedente trattamento con qualsiasi inibitore di PI3K, AKT o mTOR, o con qualsiasi agente il cui meccanismo d’azione consista nell’inibire la via di PI3K-AKT-mTOR
    • Idoneità al trattamento con chemioterapia citotossica al momento dell’ingresso nello studio, secondo le linee guida nazionali di trattamento (per es. pazienti con crisi viscerali)
    • Diabete di tipo 2 con necessità di trattamento sistemico al momento dell’ingresso nello studio; oppure anamnesi di diabete di tipo 1
    • Incapacità o riluttanza a deglutire pillole o a ricevere iniezioni intramuscolari
    • Sindrome da malassorbimento o altra patologia che potrebbe interferire con l’assorbimento enterico
    • Metastasi del SNC note e non trattate oppure attive
    • Epatopatia clinicamente significativa e attiva, inclusa grave insufficienza epatica (classe Child-Pugh B/C), epatite virale o altra epatite nota, attuale alcolismo o cirrosi
    E.5 End points
    E.5.1Primary end point(s)
    1. Progression-free survival
    1. Sopravvivenza libera da progressione (PFS)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Up to 6 years
    Fino a 6 anni
    E.5.2Secondary end point(s)
    1. Objective response rate
    2. Best overall response rate
    3. Duration of response
    4. Clinical benefit rate
    5. Overall survival
    6. Time to deterioration (TTD) in pain
    7. TTD in physical function
    8. TTD in role function
    9. TTD in GHS/HRQoL
    10. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
    11. Change from baseline in targeted vital signs
    12. Change from baseline in targeted clinical laboratory test results
    13. Change from baseline in ECG parameters
    14. Plasma concentration of GDC-0077 at specified timepoints
    15. Plasma concentration of palbociclib at specified timepoints
    16. Plasma concentration of fulvestrant at specified timepoints
    1. Tasso di risposta obiettiva (ORR)
    2. Miglior tasso di risposta complessivo (BOR)
    3. Durata della risposta (DOR)
    4. Tasso di beneficio clinico (CBR)
    5. Sopravvivenza globale (OS)
    6. Tempo al peggioramento (TTD) del dolore
    7. TTD della funzione fisica
    8. TTD delle funzioni di ruolo
    9. TTD dello stato di salute generale (GHS)/della qualità di vita correlata alla salute (HRQoL)
    10. Incidenza e gravità degli eventi avversi, classificando la gravità in base ai Criteri terminologici comuni per gli eventi avversi del National Cancer Institute, Versione 5.0 (NCI-CTCAE, v 5.0)
    11. Variazione dal basale di parametri vitali mirati
    12. Variazione dal basale dei risultati di analisi cliniche di laboratorio mirate
    13. Variazione dal basale dei parametri ECG
    14. Concentrazione plasmatica di GDC 0077 in specifici momenti di rilevazione
    15. Concentrazione plasmatica di palbociclib in specifici momenti di rilevazione
    16. Concentrazione plasmatica di fulvestrant in specifici momenti di rilevazione
    E.5.2.1Timepoint(s) of evaluation of this end point
    1-5. Up to 6 years
    6-9. Day 1 of Cycle 1, on the planned Day 1 of Cycle 2 and 3 then at the planned Day 1 of every other cycle (i.e., C5, C7, etc.) and at treatment discontinuation. During post-treatment follow-up, PROs collected every 8 weeks during the first 2 years on study, then every 12 weeks
    10. Up to 30 days after the final dose of study treatment, or until initiation of another anti-cancer therapy
    11-13. From baseline (Day 1 of Cycle 1) to 30 days after the final dose of study treatment
    14-16. Day 1, 8, 15 of Cycle 1; Day 15 of Cycle 2
    1-5. Fino a 6 anni
    6-9. Giorno 1 del Ciclo 1, al giorno 1 pianificato del Ciclo 2 e 3 e successivamente al Giorno 1 pianificato di ogni Ciclo successivo (es. C5, C7, ecc.) e all’interruzione del trattamento. Durante il follow up post trattamento, PROs raccolti ogni 8 settimane durante i primi due anni di studio, successivamente ogni 12 settimane
    10. Fino a 30 giorni dopo l’ultima dose del trattamento in studio, o fino all’inizio di una nuova terapia antitumorale.
    11-13. Dal basale (Giorno 1 del Ciclo 1) fino a 30 giorni dopo l’ultima dose del trattamento in studio
    14-16. Giorno 1, 8, 15 del Ciclo 1; Giorno 15 del Ciclo 2
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Exploratory Biomarker, Health Status Utility
    Biomarcatori esplorativi, utilità dello stato di salute
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA100
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Austria
    Belgium
    Canada
    Denmark
    France
    Germany
    Greece
    Hong Kong
    Hungary
    Italy
    Korea, Republic of
    New Zealand
    Poland
    Portugal
    Russian Federation
    Singapore
    Spain
    Taiwan
    Thailand
    Ukraine
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 280
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 120
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 223
    F.4.2.2In the whole clinical trial 400
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    A patient will be eligible to receive Roche IMP (GDC 0077) after
    completing the study if all of the following conditions are met:
    • The patient has a life-threatening or severe medical condition and
    requires continued Roche IMP treatment for his or her well-being
    • There are no appropriate alternative treatments available to the
    patientThe patient and his or her doctor comply with and satisfy any legal or
    regulatory requirements that apply to them
    please see section 4.3.5 in the protocol
    Un paziente avrà diritto a ricevere Roche IMP (GDC 0077) dopo lo studio se sono soddisfatte tutte le seguenti condizioni:
    • Il paziente ha una condizione medica grave o pericolosa per la vita e richiede un costante trattamento IMP Roche per il suo benessere
    • Non ci sono trattamenti alternativi adeguati disponibili per paziente
    • Il paziente e il suo medico rispettano e soddisfano qualsiasi diritto o requisiti normativi ad essi applicabili
    consultare la sezione 4.3.5 del protocoll
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-08-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-09-15
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA