E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HER2 Positive Early Breast Cancer |
carcinoma mammario in stadio iniziale HER2-positivo |
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E.1.1.1 | Medical condition in easily understood language |
HER2 Positive Early Breast Cancer |
carcinoma mammario in stadio iniziale HER2-positivo |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065430 |
E.1.2 | Term | HER-2 positive breast cancer |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the treatment effect of ABP 980 with trastuzumab on pathologic complete response (pCR) in women with early breast cancer
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Confrontare l’efficacia del trattamento di ABP 980 con trastuzumab sulla risposta patologica completa (pathologic Complete Response, pCR) in donne con carcinoma mammario in stadio iniziale |
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E.2.2 | Secondary objectives of the trial |
To assess the safety, tolerability, and immunogenicity of ABP 980 compared with trastuzumab
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Valutare la sicurezza, la tollerabilità, e l’immunogenicità di ABP 980 rispetto a trastuzumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Females ≥ 18 years of age
Histologically confirmed invasive breast cancer
Planning for surgical resection of breast tumor and sentinel node (SN) or axillary lymph node resection
Planning neoadjuvant chemotherapy
HER2 positive disease defined as:
3+ overexpression by immunohistochemistry (IHC) or
HER2 amplification by fluorescence in situ hybridization (FISH)
Measurable disease (assessment method used in order of priority: ultrasound, mammography, MRI, or physical examination) in the breast after diagnostic biopsy, defined as longest diameter ≥ 2.0 cm
Known ER and PR hormone receptor status at study entry
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Left ventricular ejection fraction (LVEF) of ≥ 55% by 2D echocardiogram
Normal bone marrow function as defined by:
absolute neutrophil count (ANC) > 1.5 x 10^9 g/dL (1,500/µL);
platelets > 100 x 10^9 g/dL (100,000/µL);
hemoglobin > 10.0 g/dL.
Normal hepatic function as defined by:
total bilirubin within normal institutional limits;
aspartate aminotransferase (AST) and alanine aminotransferase (ALT);
< 2.5 × the upper limit of normal (ULN);
subjects with an elevated unconjugated bilirubin (Gilbert's syndrome) will be eligible if hepatic enzymes and function are otherwise within normal limits (ie, AST, ALT, and Alkaline Phosphatase are within normal limits), and there is no evidence of hemolysis.
Normal renal function as defined by creatinine < 1.5 × ULN or estimated creatinine clearance (CrCl) ≥ 50 mL/min calculated by the Cockcroft-Gault method
Subjects must sign an IRB/EC-approved informed consent form before any study specific procedures
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• Soggetti di sesso femminile ≥ 18 anni di età
• Carcinoma mammario invasivo confermato istologicamente
• Prevista resezione chirurgica del tumore mammario e del nodulo sentinella (SN) o del linfonodo ascellare
• Prevista chemioterapia neoadiuvante
• Malattia HER2 positiva definita come:
o sovraespressione 3+ stabilita da immunoistochimica (IHC) o
o amplificazione di HER2 mediante ibridazione in situ a fluorescenza (Fluorescence In Situ Hybridization, FISH)
• Malattia misurabile (metodo di valutazione utilizzato in ordine di priorità: ultrasuoni, mammografia, RMI o esame obiettivo) alla mammella in seguito a biopsia diagnostica, definita come diametro massimo ≥ 2,0 cm
• Status del recettore ormonale per gli estrogeni (ER) e per il progesterone (PR) noto all’ingresso nello studio
• Stato di validità ECOG (Eastern Cooperative Oncology Group) pari a 0 o 1
• Frazione di eiezione ventricolare sinistra (Left Ventricular Ejection Fraction, LVEF) ≥ 55% mediante ecocardiogramma 2D
• Funzione del midollo osseo normale definita da:
o conta assoluta dei neutrofili (Absolute Neutrophil Count, ANC) > 1,5 ×109 g/dl (1.500/µl);
o piastrine > 100 × 109 g/dl (100.000/µl);
o emoglobina > 10,0 g/dl.
• Funzione epatica normale definita da:
o bilirubina totale entro i normali limiti istituzionali;
o aspartato aminotransferasi (aspartate aminotransferase, AST) e alanina aminotransferasi (alanine aminotransferase, ALT);
< 2,5 × il limite superiore della norma (Upper Limit of Normal, ULN);
o i soggetti con bilirubina non coniugata elevata (sindrome di Gilbert) saranno idonei se la funzione e gli enzimi epatici sono entro i normali limiti
(ossia se AST, ALT e fosfatasi alcalina sono entro i normali limiti) e non vi è alcuna evidenza di emolisi.
• Funzione renale normale definita come creatinina < 1,5 × ULN o clearance della creatinina (CrCl) stimata ≥ 50 ml/min calcolata con il metodo di Cockcroft-Gault
• I soggetti devono firmare un modulo di consenso informato approvato dal Comitato di Revisione Istituzionale (Institutional Review Board, IRB) e dal Comitato etico (CE) prima di qualsiasi procedura specifica dello studio
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E.4 | Principal exclusion criteria |
Bilateral breast cancer
Presence of known metastases
Received prior treatment, including chemotherapy, biologic therapy, radiation or surgery with the exception of diagnostic biopsy for primary breast cancer
Other concomitant active malignancy or history of malignancy in the past 5 years except treated basal cell carcinoma of the skin or carcinoma in situ of the cervix
Pre-existing clinically significant (≥ grade 2) peripheral neuropathy
Any history of documented or current congestive heart failure, current high-risk uncontrolled arrhythmias, current angina pectoris requiring a medicinal product, current clinically significant valvular disease, current evidence of transmural infarction on electrocardiogram (ECG), or current poorly controlled hypertension
Severe dyspnea at rest requiring supplementary oxygen therapy
History of positivity for hepatitis B surface antigen, hepatitis C virus, or HIV
Recent infection requiring a course of systemic anti-infectives that were completed
≤ 14 days before enrollment (with the exception of uncomplicated urinary tract infection)
Woman of childbearing potential who is pregnant or is breast feeding
Woman of childbearing potential who is not consenting to use highly effective methods of birth control (eg, abstinence, sterilization, birth control pills, Depo-Provera injections, or contraceptive implants) during treatment and for an additional 4 months after the last administration of the protocol specified treatment
Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study
Other investigational procedures while participating in this study are excluded
Subject has known sensitivity to any of the products to be administered during the study, including mammalian cell derived drug products, trastuzumab, murine proteins, or to any of the excipients
Subject previously has enrolled and/or has been randomized in this study
Subject likely to not be available to complete all protocol required study visits or procedures
History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the Investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion |
• Carcinoma mammario bilaterale
• Presenza di metastasi note
• Ricezione di trattamento precedente, compresi chemioterapia, terapia biologica, radiazioni o intervento chirurgico ad eccezione della biopsia diagnostica per il carcinoma mammario primario
• Altri tumori maligni attivi concomitanti o anamnesi di tumori maligni nei 5 anni precedenti eccetto carcinoma basocellulare della pelle o carcinoma in situ della cervice
• Neuropatia periferica preesistente clinicamente significativa (≥ grado 2)
• Qualsiasi anamnesi di insufficienza cardiaca congestizia documentata o attuale, attuali aritmie incontrollate ad alto rischio, attuale angina pectoris che necessita di un prodotto medicinale, attuale patologia valvolare clinicamente significativa, attuale evidenza di infarto transmurale dall’elettrocardiogramma (ECG) o attuale ipertensione scarsamente controllata
• Grave dispnea a riposo che necessita di terapia con ossigeno supplementare
• Anamnesi di positività per l’antigene superficiale dell’epatite B, virus dell’epatite C o HIV
• Infezione recente che ha richiesto un ciclo completato di antinfettivi sistemici
≤ 14 giorni prima dell’arruolamento (a eccezione di infezioni del tratto urinario senza complicazioni)
• Donne in età fertile attualmente in gravidanza o allattamento
• Donne in età fertile che non accettano di utilizzare metodi altamente efficaci per il controllo delle nascite (ad es. astinenza, sterilizzazione, pillole anticoncezionali, iniezioni di Depo-Provera o impianti contraccettivi) durante il trattamento e per ulteriori 4 mesi in seguito all’ultima somministrazione del trattamento specificato nel protocollo
• Attualmente in trattamento nell’ambito di un altro studio su farmaci o dispositivi sperimentali, o meno di 30 giorni dal termine del trattamento nell’ambito di un altro studio su farmaci o dispositivi sperimentali
• Durante la partecipazione a questo studio sono escluse altre procedure sperimentali
• Il soggetto presenta una sensibilità nota a qualsiasi prodotto da somministrarsi durante lo studio, compresi prodotti farmacologici derivati da cellule di mammiferi, trastuzumab, proteine murine o uno qualsiasi degli eccipienti
• Il soggetto si è arruolato e/o è stato randomizzato in questo studio in precedenza
• Probabilmente il soggetto non è disposto a completare tutte le visite o le procedure richieste dal protocollo
Anamnesi o evidenza di qualsiasi altro disturbo, condizione o malattia (eccetto quanto descritto sopra) clinicamente significativi che, a parere dello Sperimentatore o del medico di Amgen, se consultato, rappresenterebbe un rischio per la sicurezza del soggetto o interferirebbe con l’analisi, le procedure o il completamento dello studio
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E.5 End points |
E.5.1 | Primary end point(s) |
Risk ratio (RR) of the incidence of pathologic complete response (pCR) in breast tissue and axillary lymph nodes |
Rischio relativo (RR) dell’incidenza di risposta patologica completa (pCR) nel tessuto mammario e nei linfonodi ascellari |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Visit 10 (Initiation of investigational product adjuvant therapy cycle 1): Subjects will undergo a lumpectomy or mastectomy with sentinel node or axillary node dissection. Surgery is expected to be scheduled within 3 to 7 weeks after the last dose of investigational product in the neoadjuvant phase and pCR will be analyzed.
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Visita 10 (inizio del prodotto sperimentale nella terapia adiuvante ciclo1): I pazienti saranno sottoposti ad una asportazione della massa o mastectomia con la resezione del Nodulo Sentinella o linfonodo ascellare. L’intervento sarà completato dalle 3 alle 7 settimane dopo l’ultima dose di prodotto sperimentale nella fase neoadiuvante; e sarà analizzata la pCR. |
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E.5.2 | Secondary end point(s) |
Risk ratio (RR) of pCR in breast tissue
Risk ratio (RR) of pCR in breast tissue and axillary lymph nodes and absence of Ductal Carcinoma in Situ (DCIS)
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Rischio relativo (RR) di risposta patologica completa (pCR) nel tessuto mammario Rischio relativo (RR) di risposta patologica completa (pCR) nel tessuto mammario e nei linfonodi ascellari e assenza di carcinoma duttale in situ (Ductal Carcinoma in Situ, DCIS) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Visit 10 (Initiation of investigational product adjuvant therapy cycle 1): Subjects will undergo a lumpectomy or mastectomy with SN or axillary node dissection. Surgery is expected to be scheduled within 3 to 7 weeks after the last dose of investigational product in the neoadjuvant phase Pathology of tumor sample and pCR will then be analyzed.
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Visita 10 (inizio del prodotto sperimentale nella terapia adiuvante ciclo1): I pazienti saranno sottoposti ad una asportazione della massa o mastectomia con la resezione del Nodulo Sentinella o linfonodo ascellare. L’intervento sarà completato dalle 3 alle 7 settimane dopo l’ultima dose di prodotto sperimentale nella fase neoadiuvante; sarano analizzati La Patologia del Campione di tumore e pCR |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
ADA - anti-drug antibody testing is being performed |
verrà eseguito l’esame anticordpo anti farmaco - ADA |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belarus |
Brazil |
Bulgaria |
Canada |
Czech Republic |
Germany |
Greece |
Hungary |
Italy |
Mexico |
Peru |
Poland |
Romania |
Russian Federation |
Serbia |
Slovakia |
South Africa |
Spain |
Ukraine |
United Kingdom |
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E.8.7 | Trial 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
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The end of study (end of trial) will be the date when the last subject has their last study assessment |
la Fine dello Studio (fine della sperimentazione) sarà la data dell’ultimo paziente che avrà eseguito l’ultimo accertamento |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |