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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).


    The EU Clinical Trials Register currently displays   43974   clinical trials with a EudraCT protocol, of which   7312   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 on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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:2021-002323-38
    Sponsor's Protocol Code Number:GBG105GeparPiPPa
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2022-02-16
    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 ConcernedGermany - BfArM
    A.2EudraCT number2021-002323-38
    A.3Full title of the trial
    A randomized, open-label, phase II trial comparing neoadjuvant endocrine therapy in combination with trastuzumab, pertuzumab +/- the PI3K inhibitor inavolisib in patients with HER2-positive, HR-positive, PIK3CA mutant early breast cancer - GeparPiPPa
    Eine randomisierte, offene Phase-II-Studie zum Vergleich einer neoadjuvanten endokrinen Therapie in Kombination mit Trastuzumab, Pertuzumab +/- dem PI3K-Inhibitor Inavolisib bei Patienten mit HER2-positivem, HR-positivem, PIK3CA-mutiertem primären Brustkrebs - GeparPiPPa
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Neoadjuvant endocrine therapy in combination with trastuzumab, pertuzumab with or without inavolisib
    Neoadjuvante endokrine Therapie in Kombination mit Trastuzumab, Pertuzumab mit oder ohne Inavolisib
    A.3.2Name or abbreviated title of the trial where available
    GeparPiPPa
    GeparPiPPa
    A.4.1Sponsor's protocol code numberGBG105GeparPiPPa
    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 SponsorGerman Breast Group
    B.1.3.4CountryGermany
    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 organisation
    B.5.2Functional name of contact point
    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 nameinavolisib (GDC-0077)
    D.3.2Product code RO7113755
    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.3.8INN - Proposed INNinavolisib
    D.3.9.2Current sponsor codeRO7113755/F09-02
    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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    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 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 nameinavolisib (GDC-0077)
    D.3.2Product code RO7113755
    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.3.8INN - Proposed INNinavolisib
    D.3.9.2Current sponsor codeRO7113755/F08-02
    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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    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.2.1.1.1Trade name Phesgo
    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 namePhesgo
    D.3.2Product code RO7198574
    D.3.4Pharmaceutical form Solution for injection in vial
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPertuzumab
    D.3.9.1CAS number 380610-27-5
    D.3.9.2Current sponsor codeRO7198574
    D.3.9.3Other descriptive namePertuzumab SC as part of fixed dose combination with Trastuzumab
    D.3.9.4EV Substance CodeSUB16455MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number80
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 180288-69-1
    D.3.9.3Other descriptive nameTrastuzumab SC as part of fixed dose combination with Pertuzumab
    D.3.9.4EV Substance CodeSUB12612MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    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 Yes
    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 Yes
    D.3.11.13.1Other medicinal product typeA fixed dose combination product of 2 humanised IgG1 monoclonal antibodies (pertuzumab and trastuzumab)
    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 No
    D.2.1.1.1Trade name Phesgo
    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 namePhesgo
    D.3.2Product code RO7198574
    D.3.4Pharmaceutical form Solution for injection in vial
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPertuzumab
    D.3.9.1CAS number 380610-27-5
    D.3.9.2Current sponsor codeRO7198574
    D.3.9.3Other descriptive namePertuzumab SC as part of fixed dose combination with Trastuzumab
    D.3.9.4EV Substance CodeSUB16455MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 180288-69-1
    D.3.9.3Other descriptive nameTrastuzumab SC as part of fixed dose combination with Pertuzumab
    D.3.9.4EV Substance CodeSUB12612MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    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 Yes
    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 Yes
    D.3.11.13.1Other medicinal product typeA fixed dose combination product of 2 humanised IgG1 monoclonal antibodies (pertuzumab and trastuzumab)
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Patients with early breast cancer
    Patienten mit primärem Brustkrebs
    E.1.1.1Medical condition in easily understood language
    Patients with early breast cancer
    Patienten mit primärem Brustkrebs
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Objective:
    To compare pathological complete response (pCR=ypT0/is ypN0) rates between HER2-positive, HR-positive, PIK3CA mutant early breast cancer treated with inavolisib concurrently given to endocrine therapy, pertuzumab and trastuzumab vs. endocrine therapy, pertuzumab and trastuzumab alone.
    Endpoint: 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.
    Ziel:
    Vergleich der pathologischen Komplettremissionsraten (pCR=ypT0/is ypN0) bei HER2-positivem, HR-positivem, PIK3CA-mutiertem Brustkrebs im Frühstadium, der entweder mit Inavolisib in Kombination mit einer endokrinen Therapie und Pertuzumab und Trastuzumab behandelt wurde, im Vergleich zu endokriner Therapie, Pertuzumab und Trastuzumab allein.
    Endpunkt: Eine Pathologische Komplettremission (ypT0/ist ypN0) ist definiert als kein mikroskopischer Nachweis restlicher invasiver Tumorzellen in allen resezierten Präparaten der Brust und Axilla.
    E.2.2Secondary objectives of the trial
    • To determine the rates of ypT0 ypN0; ypT0 ypN0/+; ypT0/is ypN0/+; ypT(any) ypN0
    • To assess the pCR rates per arm separately for the stratified subpopulations
    • To determine the response rates of the breast tumor and axillary nodes based on physical
    examination and imaging tests after study treatment in both arms
    • To determine the percentage of patients receiving additional neoadjuvant chemotherapy after
    residual disease was confirmed by core biopsy at the end of study treatment
    • To determine the breast conservation rate after each treatment
    • To assess early safety and tolerability after the first 20 and the first 40 have completed two cycles of therapy
    • To assess the overall safety and tolerability and treatment compliance in the two arms
    • Invasive disease-free survival (IDFS) and overall survival (OS) in both arms and according to stratified subpopulations.The timing for the time-to-event endpoints analysis will be defined in the statistical analysis plan.
    • Bestimmung der Raten von ypT0 ypN0; ypT0 ypN0/+; ypT0/is ypN0/+; ypT(beliebig) ypN0
    • Bestimmung der pCR-Raten pro Arm für die stratifizierten Subgruppen
    • Bestimmung der Ansprechraten des Brusttumors und der axillären Lymphknoten anhand körperlicher und der bildgebender Untersuchung in beiden Armen
    • Bestimmung des Anteils der Patienten mit zusätzlicher neoadjuvanter Chemotherapie nach Bestätigung von Tumorrest anhand Stanzbiopsie nach der Studienbehandlung
    • Bestimmung der Brusterhaltungsrate nach jeder Behandlung
    • Frühzeitige Beurteilung der Sicherheit und Toxizität, nachdem die ersten 20 und 40 Patienten zwei Therapiezyklen abgeschlossen haben
    • Beurteilung der Sicherheit und Verträglichkeit sowie der Therapiecompliance in beiden Armen
    • Invasives krankheitsfreies Überleben (IDFS) und Gesamtüberleben (OS) in beiden Armen und nach stratifizierten Subpopulationen. Der Zeitpunkt für die Analyse der Time-to-Event-Endpunkte wird im statistischen Analyseplan festgelegt.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients will be eligible for study participation only if they comply with the following criteria:
    1. Written informed consent for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures.
    2. Untreated, unilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration alone is not sufficient. Incisional biopsy is not allowed..
    3. Tumor lesion in the breast with a palpable size of ≥ 2 cm or a sonographical size of ≥ 1 cm in maximum diameter. The lesion has to be measurable in two dimensions, preferably by sonography.
    4. Patients must be in the following stages of disease:
    • cT1c – cT3
    In patients with multifocal or multicentric breast cancer the largest lesion (target lesion) should be measured.
    5. HR+/HER2+ disease with centrally confirmed ER-status, PR-status, HER2-status, PIK3CA mutation (tumor), Ki-67 value and TILs on core biopsy (target lesion). ER/PgR positive and HER2-positive is defined according to current ASCO/CAP guidelines. PIK3CA mutational status will be determined by NGS. Formalin-fixed, paraffin-embedded (FFPE) breast tissue from core biopsy has therefore to be sent to the GBG central pathology laboratory prior to randomization.
    6. Age  18 years, female and male.
    7. ECOG Performance status 0-1.
    8. Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF or shortening fraction) within 3 months prior to randomization. Results for LVEF must be above 55%.
    9. Laboratory requirements:
    Hematology
    • Absolute neutrophil count (ANC)  1.5/ nL
    • Platelets  100/ nL and
    • Hemoglobin  10 g/dL ( 6.2 mmol/L)
    Hepatic function
    • Total bilirubin < ULN except for patients with Gilbert’s syndrome who may only be included if the total bilirubin is ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN
    • AST and ALT  1.5x ULN and
    • Alkaline phosphatase  2.5x ULN
    Glucose Metabolism:
    • Fasting plasma glucose (FPG) < 126 mg/dL (7.0 mmol/L)
    • Glycosylated hemoglobin (HbA1c) < 5.7%
    10. Negative pregnancy test (urine or serum) within 14 days prior to randomization for all women of childbearing potential. A woman is considered to be of childbearing potential if she is not hysterectomised or not postmenopausal.
    Postmenopausal is defined as:
    • Age 60 years.
    • Age <60 years and 12 continuous months of amenorrhea with no identified cause other than menopause.
    • Surgical sterilization (bilateral oophorectomy).
    11. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of  1% per year during the treatment period and for least 7 months after the last dose of PH-FDC SC. Examples of non hormonal contraceptive methods with a failure rate of  1% per year include: bilateral tubal ligation; male partner sterilization; intrauterine devices. For men: men must remain abstinent or use a condom with a spermicidal product during the treatment period and for 7 months after the last dose of PH-FDC therapy to avoid exposing the embryo. Men and women must refrain from donating sperm/eggs during this same period.
    12. Complete staging work-up within prior to randomization with:
    • Bilateral mammography and/or breast MRI in combination with a breast ultrasound
    • Staging according to country guidelines
    • Other tests may be performed as clinically indicated.
    13. Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
    Patienten werden nur dann zur Studienteilnahme zugelassen, wenn sie die folgenden Kriterien erfüllen:
    1. Schriftliche Einverständniserklärung für alle Studienprozeduren gemäß den lokalen behördlichen Anforderungen vor Beginn der spezifischen Protokollbehandlung.
    2. Unbehandeltes, einseitiges Karzinom der Brust, histologisch bestätigt durch Stanzbiopsie. Eine Feinnadelaspiration allein ist nicht ausreichend. Eine Inzisionsbiopsie ist nicht erlaubt.
    3. Tumorläsion in der Brust mit einer palpablen Größe von ≥ 2 cm oder einer sonographischen Größe von ≥ 1 cm im maximalen Durchmesser. Die Läsion muss in zwei Dimensionen messbar sein, vorzugsweise durch Sonographie.
    4. Die Patienten müssen sich in einem der folgenden Stadien der Erkrankung befinden:
    • cT1c - cT3
    Bei Patientinnen mit multifokalem oder multizentrischem Brustkrebs sollte die größte Läsion (Zielläsion) gemessen werden.
    5. HR+/HER2+ Erkrankung mit zentral bestätigtem ER-Status, PR-Status, HER2-Status, PIK3CA-Mutation (Tumor), Ki-67-Wert und TILs anhand der Stanzbiopsie (Zielläsion). ER/PgR-positiv und HER2-positiv wird gemäß den aktuellen ASCO/CAP-Richtlinien definiert. Der PIK3CA-Mutationsstatus wird mittels NGS bestimmt. Formalin-fixiertes, paraffin-eingebettetes (FFPE) Brustgewebe von der Stanzbiopsie muss daher vor der Randomisierung an die Zentralpathologie der GBG geschickt werden.
    6. Alter 18 Jahre, weiblich und männlich.
    7. ECOG Performance Status 0-1.
    8. Eine normale Herzfunktion muss durch EKG und Herzultraschall (LVEF oder Verkürzungsfraktion) innerhalb von 3 Monaten vor der Randomisierung bestätigt werden. Die Ergebnisse für die LVEF müssen über 55 % liegen.
    9. Anforderungen an das Labor:
    Hämatologie
    • Absolute Neutrophilenzahl (ANC)  1,5/ nL
    • Thrombozyten 100/nL und
    • Hämoglobin  10 g/dL ( 6,2 mmol/L)
    Hepatische Funktion
    • Gesamtbilirubin < ULN, außer bei Patienten mit Gilbert-Syndrom, die nur eingeschlossen werden dürfen, wenn das Gesamtbilirubin
    ≤ 3,0 × ULN oder das direkte Bilirubin ≤ 1,5 × ULN ist
    • AST und ALT ≤ 1,5 x ULN und
    • Alkalische Phosphatase ≤ 2,5 x ULN
    Glukose-Stoffwechsel:
    • Nüchtern-Plasmaglukose (FPG) < 126 mg/dL (7,0 mmol/L)
    • Glykosyliertes Hämoglobin (HbA1c) < 5,7%
    10. Negativer Schwangerschaftstest (Urin oder Serum) innerhalb von 14 Tagen vor der Randomisierung für alle gebärfähigen Frauen. Eine Frau gilt als gebärfähig, wenn sie nicht postmenopausal ist oder keine Gebärmutterentfernung hatte..
    Postmenopausal ist definiert als:
    • Alter 60 Jahre.
    • Alter  60 Jahre und  12 ununterbrochene Monate Amenorrhoe ohne erkennbare Ursache außer der Menopause.
    • Chirurgische Sterilisation (bilaterale Oophorektomie).
    11. Für gebärfähige Frauen: Vereinbarung, abstinent zu bleiben (auf heterosexuellen Geschlechtsverkehr zu verzichten) oder Verhütungsmethoden mit einer Versagerrate von 1 % während des Behandlungszeitraums und für mindestens 7 Monate nach der letzten Dosis von PH-FDC SC anzuwenden. Beispiele für nicht hormonelle Verhütungsmethoden mit einer Versagerrate von 1 % pro Jahr sind: bilaterale Tubenligatur; Sterilisation des männlichen Partners; Intrauterinpessare. Für Männer: Männer müssen während des Behandlungszeitraums und für 7 Monate nach der letzten Dosis der PH-FDC-Therapie abstinent bleiben oder ein Kondom mit einem spermiziden Produkt verwenden, um eine Exposition des Embryos zu vermeiden. Männer müssen in diesem Zeitraum auf eine Samenspende verzichten.
    12. Vollständige Staging-Untersuchung vor der Randomisierung mit:
    • Beidseitiger Mammographie und/oder Brust-MRT in Kombination mit einem Brust-Ultraschall
    • Staginguntersuchungen gemäß nationalen Leitlinien
    • Andere Tests können je nach klinischer Indikation durchgeführt werden.
    13. Der Patient muss bereit und in der Lage sein, die geplanten Besuche, Behandlungspläne, Labortests und andere Studienverfahren einzuhalten.
    E.4Principal exclusion criteria
    Patients will be ineligible for study participation if they comply with the following criteria:
    1. Patients with HER2-negative breast cancer and/or HER2-positive, HR-negative breast cancer
    2. Need of immediate neoadjuvant chemotherapy, e.g. inflammatory breast cancer
    3. Patients with definitive clinical or radiologic evidence of Stage IV cancer.
    4. Excisional biopsy or lumpectomy and /or axillary lymph node dissection and/or sentinel lymph node biopsy performed prior to study entry (biopsy of clinical involved LN is warranted).
    5. Prior chemotherapy or endocrine therapy or radiation therapy prior to study entry.
    6. Patients with a history of breast cancer are ineligible with the following exceptions:
    • Patient has been disease-free for more than 5 years and is at low risk for recurrence (at the investigator’s discretion).
    7. Patients with a history of any treated malignancy are ineligible in case of high risk of recurrence (at the investigator’s discretion) and/or ongoing oncological treatment. This also applies to patients who are at high risk that oncological treatment is indicated during study therapy.
    8. BMI>30
    9. Known hypersensitivity reaction to one of the compounds or substances, and/or murine proteins, and/or recombinant human hyaluronidase used in this protocol.
    10. Patients with an established diagnosis of diabetes mellitus type I or uncontrolled type II based on FPG and HbA1c.
    11. Patients who are immunocompromised as the result of HIV or receiving immunosuppressive therapies.
    12. Clinically significant and active liver disease, for example, sclerosing cholangitis, active viral hepatitis B or C infection, or autoimmune hepatic disorders.
    13. Patients with inflammatory bowel disease, such as Crohn’s disease or
    ulcerative colitis, and active bowel inflammation (e.g., diverticulitis).
    14. Patients with any concurrent ocular or intraocular condition, such as cataract or diabetic retinopathy, that would require medical or surgical intervention during the study period to prevent or treat vision loss. In addition, patients with active uveitis or vitritis, history of uveitis, or active infectious process in the eye.
    15. Patients with currently documented pneumonitis/interstitial lung disease.
    16. Known or suspected congestive heart failure (>NYHA I) and / or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, uncontrolled or poorly controlled arterial hypertension (i.e. BP >160 / 90 mm Hg under treatment with three antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease.
    17. Damaged skin at planned site of subcutaneous (SC) injections (thigh).
    18. Patients who may have had a recent episode of thromboembolism and are still trying to optimize the anticoagulation dose and/or have not normalized their INR.
    19. Concurrent treatment with:
    • Chronic corticosteroids unless initiated > 6 months prior to study entry and at low dose (10 mg or less methylprednisolone or equivalent).
    • Sex hormones. Prior treatment must be stopped before study entry. (GnRH a is allowed)
    • Other experimental drugs or any other anti-cancer therapy.
    20. Participation in another clinical trial with any investigational, not marketed drug within 30 days prior to study entry.
    21. Female patients: pregnancy or lactation at the time of randomization.
    22. History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent.
    23. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
    Patienten werden von der Studienteilnahme ausgeschlossen, wenn sie die folgenden Kriterien erfüllen:
    1. Patientinnen mit HER2-negativem Brustkrebs und/oder HER2-positivem, HR-negativem Brustkrebs
    2. Notwendigkeit einer sofortigen neoadjuvanten Chemotherapie, z. B. bei inflammatorischem Brustkrebs
    3. Patienten mit definitivem klinischem oder radiologischem Nachweis von Krebs im Stadium IV.
    4. Exzisionsbiopsie oder Lumpektomie und/oder axilläre Lymphknotendissektion und/oder Sentinel-Lymphknoten-Biopsie, die vor Studienbeginn durchgeführt wurde ( eine Biopsie von klinisch positiven Lymphknoten ist erlaubt).
    5. Vorherige Chemotherapie oder endokrine Therapie oder Strahlentherapie vor Studienbeginn.
    6. Patienten mit Brustkrebs in der Vorgeschichte sind mit den folgenden Ausnahmen nicht zugelassen:
    • Der Patient ist seit mehr als 5 Jahren krankheitsfrei und hat ein geringes Risiko für ein Rezidiv (nach Ermessen des Prüfarztes).
    7. Patienten mit einer Vorgeschichte eines behandelten Malignoms sind nicht teilnahmeberechtigt, wenn ein hohes Risiko für ein Rezidiv (nach Ermessen des Prüfarztes) und/oder eine laufende onkologische Behandlung besteht. Dies gilt auch für Patienten, bei denen ein hohes Risiko besteht, dass eine onkologische Behandlung während der Studientherapie angezeigt ist.
    8. BMI>30
    9. Bekannte Überempfindlichkeitsreaktion auf eine der in diesem Protokoll verwendeten Verbindungen oder Substanzen und/oder murinen Proteine und/oder rekombinante humane Hyaluronidase.
    10. Patienten mit einer Diagnose von Diabetes mellitus Typ I oder unkontrolliertem Typ II basierend auf FPG und HbA1c.
    11. Patienten, die aufgrund von HIV immungeschwächt sind oder immunsuppressive Therapien erhalten.
    12. Klinisch signifikante und aktive Lebererkrankung, z. B. sklerosierende Cholangitis, aktive Virushepatitis B oder C-Infektion oder Autoimmunerkrankungen der Leber.
    13. Patienten mit entzündlichen Darmerkrankungen, wie z. B. Morbus Crohn oder Colitis ulcerosa und aktive Darmentzündungen (z. B. Divertikulitis).
    14. Patienten mit einer gleichzeitigen okulären oder intraokularen Erkrankung, wie z. B. Katarakt oder diabetische Retinopathie, die einen medizinischen oder chirurgischen Eingriff während des Studienzeitraums erfordern würde, um einen Sehverlust zu verhindern oder zu behandeln. Außerdem Patienten mit aktiver Uveitis oder Vitritis, einer Uveitis in der Vorgeschichte oder einem aktiven infektiösen Prozess im Auge.
    15. Patienten mit aktuell dokumentierter Pneumonitis/interstitieller Lungenerkrankung.
    16. Bekannte oder vermutete kongestive Herzinsuffizienz (>NYHA I) und / oder koronare Herzkrankheit, Angina pectoris, die eine antianginöse Medikation erfordert, Myokardinfarkt in der Vorgeschichte, Nachweis eines transmuralen Infarkts im EKG, unkontrollierte oder schlecht kontrollierte arterielle Hypertonie (d. h. Blutdruck >160 / 90 mm Hg unter Behandlung mit drei blutdrucksenkenden Medikamenten), Rhythmusstörungen, die eine dauerhafte Behandlung erfordern, klinisch signifikante Herzklappenerkrankungen.
    17. Beschädigte Haut an der geplanten Stelle der subkutanen (SC) Injektion (Oberschenkel).
    18. Patienten, die kürzlich eine Thromboembolie-Episode hatten und noch versuchen, die Antikoagulationsdosis zu optimieren und/oder ihren INR-Wert nicht normalisiert haben.
    19. Gleichzeitige Behandlung mit:
    • Chronischen Kortikosteroiden, es sei denn, sie wurden > 6 Monate vor Studienbeginn begonnen und in niedriger Dosis (10 mg oder weniger Methylprednisolon oder Äquivalent).
    • Sexualhormone. Die vorherige Behandlung muss vor Studienbeginn beendet sein. (GnRHa ist erlaubt)
    • Andere experimentelle Medikamente oder eine andere Anti-Krebs-Therapie.
    20. Teilnahme an einer anderen klinischen Studie mit einem Prüfpräparat, das nicht auf dem Markt ist, innerhalb von 30 Tagen vor Studienbeginn.
    21. Weibliche Patienten: Schwangerschaft oder Stillzeit zum Zeitpunkt der Randomisierung
    22. Anamnese signifikanter neurologischer oder psychiatrischer Störungen, einschließlich psychotischer Störungen, Demenz oder Krampfanfällen, die das Verständnis und die Erteilung einer informierten Einwilligung unmöglich machen würden.
    23. Jeder Zustand, der nach Meinung des Prüfarztes die Bewertung der Studienbehandlung oder die Interpretation der Patientensicherheit oder der Studienergebnisse beeinträchtigen würde.
    E.5 End points
    E.5.1Primary end point(s)
    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.
    Eine Pathologische Komplettremission (ypT0/ist ypN0) ist definiert als kein mikroskopischer Nachweis restlicher invasiver Tumorzellen in allen resezierten Präparaten der Brust und Axilla.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Pathological response will be assessed considering all removed breast and lymphatic tissues from all surgeries. Patients without residual tumor in the biopsy should undergo surgery or are considered as no pCR, as well as all pCRs which cannot be determined); patients with additional treatment (after biopsy or without biopsy) will be considered as no pCR for the study regardless of the response to the further neoadjuvant treatment. Additional neoadjuvant treatment without definitive pCR assessment by surgery after the end of the study Treatment is to be avoided. To avoid decrease of the pCR rate of the study, these numbers will be monitored. In order not to compromise the power of the study additional patients will be recruited if this scenario affects more than 10% of the patients.
    Das pathologische Ansprechen wird unter Berücksichtigung von allem OP-Gewebe bewertet. Patienten ohne Resttumor in der Biopsie sollten sich einer Operation unterziehen (andernfalls werden sie als non-pCR betrachtet wie die Fälle, in denen diese nicht bestimmt werden kann).; Patienten mit zusätzlicher Behandlung werden als non-pCR betrachtet, unabhängig vom Ansprechen auf die weitere neoadjuvante Behandlung. Zusätzliche neoadjuvante Behandlung ohne definitive pCR-Bestimmung nach dem Ende der Studienbehandlung soll vermieden werden. Zur Vermeidung der Verringerung der pCR-Rate in der Studie werden diese Fälle während der Studie überwacht. Um die Aussagekraft der Studie nicht zu beinträchtigen werden zusätzliche Patienten rekrutiert, wenn dieses Szenario mehr als 10% der Patienten betrifft
    E.5.2Secondary end point(s)
    • To determine the rates of ypT0 ypN0; ypT0 ypN0/+; ypT0/is ypN0/+; ypT(any) ypN0
    • To assess the pCR rates per arm separately for the stratified subpopulations
    • To determine the 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
    • To determine the percentage of patients receiving additional neoadjuvant chemotherapy after residual disease was confirmed by core biopsy at the end of study treatment
    • To determine the breast conservation rate after each treatment
    • To assess early safety and tolerability after the first 20 and the first 40 patients who started therapy have completed two cycles of therapy
    • To assess the overall safety and tolerability and treatment compliance in the two arms
    • Invasive disease-free survival (IDFS) and overall survival (OS) in both arms and according to stratified subpopulations (data collected within a registry).The timing for the time-to-event endpoints analysis will be defined in the statistical analysis plan.
    • Bestimmung der Raten von ypT0 ypN0; ypT0 ypN0/+; ypT0/is ypN0/+; ypT(beliebig) ypN0
    • Bestimmung der pCR-Raten pro Arm für die stratifizierten Subgruppen
    • Bestimmung der Ansprechraten des Brusttumors und der axillären Lymphknoten anhand der körperlichen und der bildgebenden Untersuchungen (Sonographie, Mammographie oder MRT) nach der Studienbehandlung in beiden Armen
    • Bestimmung des Anteils der Patienten, die eine zusätzliche neoadjuvante Chemotherapie erhalten, nachdem ein Tumorrest durch eine Stanzbiopsie am Ende der Studienbehandlung bestätigt wurde
    • Bestimmung der Brusterhaltungsrate nach jeder Behandlung
    • Frühzeitige Beurteilung der Sicherheit und Toxizität, nachdem die ersten 20 und 40 Patienten, die mit der Therapie begonnen haben, zwei Therapiezyklen abgeschlossen haben
    • Beurteilung der Sicherheit und Verträglichkeit sowie der Therapiecompliance in den beiden Armen
    • Invasives krankheitsfreies Überleben (IDFS) und Gesamtüberleben (OS) in beiden Armen und nach stratifizierten Subpopulationen (Daten werden innerhalb eines Registers gesammelt). Der Zeitpunkt für die Analyse der Time-to-Event-Endpunkte wird im statistischen Analyseplan festgelegt.
    E.5.2.1Timepoint(s) of evaluation of this end point
    • 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, however, if sonography appears not to provide valid results or is not performed, MRI, mammography or palpation will be considered with decreasing priority. The same imaging method should be considered for the measurement before, during and after treatment.
    • 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.
    • Das klinische (c) und bildgebende (i) Ansprechen wird in jedem 2. Zyklus und vor der Operation durch körperliche Untersuchung und bildgebende Tests beurteilt. Die Sonographie ist die bevorzugte Untersuchung. Wenn jedoch die Sonographie keine gültigen Ergebnisse zu liefern scheint oder nicht durchgeführt wird, werden MRT, Mammographie oder Palpation mit abnehmender Priorität in Betracht gezogen. Das gleiche bildgebende Verfahren sollte für die Messung vor, während und nach der Behandlung in Betracht gezogen werden.
    • Überlebensendpunkte sind definiert als die Zeitspanne zwischen Randomisierung und erstem Ereignis und werden nach Ende der Studie anhand von Daten aus den Registern der GBG analysiert.
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    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 No
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    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 No
    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 concerned20
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA45
    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 No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Switzerland
    Germany
    Italy
    Belgium
    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
    Regular end-of-study is defined with the primary objective pCR. Planned end of study is QI/2026.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months9
    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: 170
    F.1.3Elderly (>=65 years) No
    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 Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    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 state90
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 145
    F.4.2.2In the whole clinical trial 170
    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)
    No study specific treatment or investigation is planned after end of neoadjuvant treatment, surgery and subsequent treatment after surgery are not part of this study.
    However, information on the health status of the patients will be collected within the GBG longterm registry of previous study participants (EternityB). German patients also have the possibility to participate in the patient self reporting registry (Patientenselbstauskunft).
    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 Decision2022-08-29
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-05-06
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA