| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| locally advanced or metastatic breast cancer |
| carcinoma della mammella localmente avanzato oppure metastatico |
|
| E.1.1.1 | Medical condition in easily understood language |
| locally advanced or metastatic breast cancer |
| carcinoma della mammmella localmente avanzato oppure metastatico |
|
| 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 | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10027475 |
| E.1.2 | Term | Metastatic breast cancer |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10072740 |
| E.1.2 | Term | Locally advanced breast cancer |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 efficacy of concomitant chemotherapy and AI versus chemotherapy followed by AI in terms of PFS. |
| Confrontare l’efficacia di chemio-endocrinoterapia concomitante e chemioterapia seguita da endocrinoterapia in termini di sopravvivenza libera da progressione (PFS). |
|
| E.2.2 | Secondary objectives of the trial |
To compare between the two treatment strategies:
• quality of life
• toxicity
• time to treatment failure (TTF)
• time to progression to the therapeutic strategy
• best response rates overall and during chemotherapy
• duration of response
• clinical benefit rate
• overall survival
• To assess correlative biomarkers of response to chemotherapy and endocrine therapy:
- tissue markers (on the primary tumor and / or metastatic tissue)
- circulating markers (e.g. CTCs, ctDNA)
|
Confrontare i due bracci di trattamento in termini di:
• qualità di vita (EORTC QLQ-C30 and QLQ-BR23)
• tossicità (CTCAE version 4.03)
• tempo al fallimento terapeutico
• tempo alla progressione della strategia terapeutica
• tasso di migliore risposta
• durata della risposta
• tasso di beneficio clinico
• sopravvivenza globale (OS)
• biomarcatori di risposta alla chemioterapia e all’endocrinoterapia:
– marcatori tissutali (sul tumore primitivo e/o sul tessuto metastatico)
– marcatori circolanti (per esempio CTCs, ctDNA)
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Age ≥ 18 years.
2) Male or female
3) Histological diagnosis of HER2-negative luminal breast cancer (ER >10% of tumor cells), determined by local laboratory on most recent available tumor tissue.
4) Locally advanced (not susceptible to locoregional therapy) or metastatic disease (herein globally defined as advanced breast cancer, ABC).
5) Candidate to chemotherapy-based treatment per the investigator best judgment; e.g. because of disease aggressiveness, short disease-free interval, elevated Ki67 [if available on a metastatic site], low expression of hormone receptors, extended visceral involvement, visceral involvement at risk for organ failure, uncontrolled symptoms), according to Associazione Italiana di Oncologia Medica (AIOM) Guidelines (2016 edition).
6) Postmenopausal women, or premenopausal women undergoing treatment with LHRH analog, or men (either receiving treatment with LHRH analog or not). Postmenopausal status is defined as:
a. bilateral, surgical oophorectomy
b. age ≥60 years
c. age <60 years, with amenorrhea >12 months and follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol concentrations within postmenopausal range
d. age <60 years and previous simple hysterectomy, with FSH, LH and estradiol levels within the post-menopausal range at two consecutive assessments two weeks apart.
7) Measurable disease according to RECIST 1.1 criteria or non measurable but evaluable lesions.
8) No prior chemotherapy for ABC. Up to two prior lines of endocrine therapy for ABC, as well as targeted therapies (such as palbociclib and/or everolimus or investigative targeted therapies) administered as part of a prior hormonal regimen for ABC, are allowed.
9) Eastern Cooperative Oncology Group performance status (ECOG-PS) ≤2
10) Adequate organ (renal, hepatic, bone marrow, cardiac) functions.
11) Female participants of child-bearing potential and male participants whose partner is of child bearing potential must be willing to use effective contraception during the study period and for 4 months thereafter. Effective contraception methods include: total abstinence (when this is in line with the preferred and usual lifestyle of the subject); tubal ligation; male sterilization; combination of the placement of an intrauterine device or intrauterine system and barrier methods of contraception with spermicidal suppository.
12) Participant is willing and able to give informed consent for participation in the study
|
1) Età ≥ 18 anni.
2) Sesso femminile o maschile.
3) Diagnosi istologica di carcinoma mammario HER2-negativo di sottotipo luminale (ER >10%), determinata localmente sul più recente tessuto tumorale disponibile.
4) Malattia localmente avanzata (non suscettibile di trattamento locoregionale) o metastatica.
5) Paziente candidato a un trattamento chemioterapico secondo il miglior giudizio clinico, per es. in caso di: malattia particolarmente aggressiva; ridotto intervallo libero da malattia; Ki67 elevato; ridotta espressione dei recettori ormonali; esteso interessamento viscerale di malattia, eventualmente con rischio di crisi d’organo imminente; sintomatologia non controllata; ecc., in accordo con le linee guida dell’Associazione Italiana di Oncologia Medica (AIOM), edizione 2016.
6) Donna in stato post-menopausale, o pre-menopausale in procinto di avviare un trattamento con LHRH analogo (per gli uomini è consentito ma non obbligatorio il trattamento con LHRH analogo).
7) Malattia misurabile secondo i criteri RECIST 1.1, o malattia non misurabile ma valutabile.
8) Prima linea chemioterapica per malattia metastatica. Sono consentiti fino a 2 precedenti trattamenti ormonoterapici in setting metastatico, in combinazione o meno con terapie target (per es. palbociclib, everolimus, ecc.).
9) ECOG Performance Status ≤2.
10) Adeguata funzione d’organo (midollare, renale, epatica, cardiaca).
11) Adozione di adeguate misure contraccettive.
12) Consenso informato scritto.
|
|
| E.4 | Principal exclusion criteria |
1) Any prior chemotherapy for advanced breast cancer
2) Resistance to both non-steroidal and steroidal aromatase inhibitors, eg patients who progressed while on or within 12 months after the end of an aromatase inhibitor in the adjuvant setting and who progressed while on an aromatase inhibitor (of a different class) in the metastatic setting, or patients who progressed to both classes of aromatase inhibitors administered as two distinct lines of therapy for metastatic disease.
3) Active central nervous system metastases.
4) Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (patients with history of hepatitis B must undergo prophylactic therapy with lamivudine or other agent according to infectious disease consultation), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
5) Prior history of non‐breast malignancy (except for adequately controlled basal cell carcinoma of the skin, carcinoma in situ of the cervix, in situ carcinoma of the bladder), unless treated with curative intent and disease free for at least 3 years.
|
1) Aver già eseguito un qualsivoglia trattamento chemioterapico in setting metastatico.
2) Resistenza a entrambe le categorie di inibitori dell’aromatasi (steroideo e non steroideo).
3) Presenza di metastasi encefaliche attive.
4) Patologie concomitanti che compromettano la possibilità di aderire alle procedure previste dal protocollo.
5) Precedente neoplasia non mammaria, se non insorta entro i 3 anni dall’arruolamento e non trattata con intento curativo (carcinomi basocellulari cutanei e carcinomi in situ sono consentiti). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| To compare the efficacy of concomitant chemotherapy and AI versus chemotherapy followed by AI in terms of progression free survival (PFS). |
| Confrontare l’efficacia di chemio-endocrinoterapia concomitante e chemioterapia seguita da endocrinoterapia in termini di sopravvivenza libera da progressione (PFS). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
| To compare overall survival (OS) between treatment arms |
| Confrontare i due bracci di trattamento in termini di sopravvivenza globale (OS) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | No |
| 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 |
| QoL and correlative biomarkers of response to chemotherapy and endocrine therapy |
| QoL ed analisi di biomarcatori di risposta alla chemioterapia e all’endocrinoterapia |
|
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| confronto tra chemio-endocrinoterapia concomitante e chemioterapia seguita da endocrinoterapia |
| to compare concomitant chemo-endocrine therapy versus chemotherapy followed by endocrine therapy |
|
| 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 | 11 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 11 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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