E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced or metastatic breast cancer resistant to aromatase inhibitor
therapy. |
Carcinoma della mammella avanzato o metastatico resistente alla terapia con inibitori dell'aromatasi. |
|
E.1.1.1 | Medical condition in easily understood language |
Breast cancer |
Carcinoma della mammella |
|
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 | SOC |
E.1.2 | Classification code | 10029104 |
E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 evaluate the efficacy (PFS) of fulvestrant + GDC-0941 and fulvestrant + GDC-0980 versus fulvestrant + placebo in all treated patients and in patients with PIK3CA mutations and/or PTEN loss
- To evaluate the safety of fulvestrant + GDC-0941 and fulvestrant + GDC-0980 versus fulvestrant + placebo |
- Valutare l'efficacia (PFS) di fulvestrant + GDC-0941 e fulvestrant + GDC-9080 rispetto a fulvestrant + placebo in tutti i pazienti trattati e nei pazienti con mutazioni PI3KCA e/o perdita di PTEN
- Valutare la sicurezza di fulvestrant + GDC-0941 e fulvestrant + GDC-0980 rispetto a fulvestrant + placebo |
|
E.2.2 | Secondary objectives of the trial |
- To assess other clinical activity and efficacy parameters of fulvestrant+GDC-0941 and fulvestrant + GDC-0980 versus fulvestrant + placebo in all treated patients and in patients with PIK3CA mutations and/or PTEN
loss |
- Misurare altri parametri di attività clinica ed efficacia di fulvestrant+GDC-0941 e fulvestrant + GDC-0980 rispetto a fulvestrant + placebo in tutti i pazienti trattati e nei pazienti con mutazioni PI3KCA e/o perdita di PTEN |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 18 years
2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
3. Postmenopausal women with locally advanced breast cancer or MBC whose disease relapsed during treatment with (or within 6 months after discontinuation of) an AI in the adjuvant setting or progressed during
treatment with an AI in the metastatic setting. The AI must be most recent treatment prior to enrollment and patients must have received at least 4 weeks of treatment with an AI prior to recurrence or disease progression.
4. ER-positive disease and HER2-negative disease
5. Measurable disease or non-measurable disease
6. Adequate hematologic and end-organ function |
1. Età ≥ 18 anni
2. ECOG Performance Status = 0 o 1
3. Donne in postmenopausa con carcinoma della mammella localmente avanzato o metastatico recidivante durante il trattamento (o entro 6 mesi dopo l'interruzione del trattamento) con un inibitore dell'aromatasi (AI) in condizione adiuvante o progredito durante il trattamento con un AI in condizione metastatica. L'AI deve essere il più recente trattamento prima dell'arruolamento e i pt devono aver ricevuto almeno 4 settimane di trattamento con un AI prima della ricaduta e della progressione di malattia.
4. malattia ER-positiva e malattia HER-2 negativa
5. Malattia misurabile o malattia non-misurabile
6. Ematologia adeguata e funzionalità dei recettori periferici |
|
E.4 | Principal exclusion criteria |
1. Prior treatment with fulvestrant, PI3K inhibitor, or mTOR inhibitor for
advanced breast cancer or MBC
2. Prior anti-cancer therapy or radiotherapy within 2 weeks prior to Day 1 of Cycle 1
3. Prior treatment with > 1 cytotoxic chemotherapy regimens or > 2 endocrine therapies for MBC
4. Patients requiring anti-hyperglycemic therapy
5. History of clinically significant cardiac or pulmonary dysfunction
6. Clinically significant history of liver disease, including cirrhosis,
current alcohol abuse, or current known active infection with hepatitis B
virus, or hepatitis C virus
7. Need for current chronic corticosteroid therapy
8. Known untreated or active CNS metastases |
1. Precedente trattamento per carcinoma della mammella avanzato o metastatico con fulvestrant, inibitori di PI3K o inibitori di mTOR
2. Precedete terapia anti-cancro o radioterapia entro le 2 settimane precedenti al giorno 1 del ciclo 1
3. Precedente trattamento con > 1 regime chemioterapico citotossico o > 2 terapie endocrine per MBC
4. Pt che richiedono terapia anti-glicemica
5. Storia di disfunzioni cardiache o polmonari clinicamente significative
6. Storia clinicamente significativa di malattie del fegato, incluse cirrosi, attuale abuso di alcool o attuale conosciuta infezione attiva con virus dell'epatite B o dell'epatite C
7. Necessità di terapia cronica attuale con corticosteroidi
8. Metastasi note del SNC non trattate o attive |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy outcome measure in all treated patients and in patients with PI3K pathway abnormalities is:
- PFS, defined as the time from the first dose of fulvestrant on Cycle 1
Day 1 to the first observation of disease progression as assessed by the
investigator per modified RECIST version 1.1 or death from any
cause on study (<= 30 days after the last dose of study treatment) |
La misurazione dell'obiettivo primario di efficacia in tutti i pazienti e nei pazienti con anormalità nel pathway di PI3K è:
- PFS, definita come il tempo tra la prima dose di fulvestrant al ciclo 1, giorno 1 e la prima ossrvazione di progressione di malattia, valutata dallo sperimentatore mediante RECIST, versione 1.1 modificata, o morte per qualsiasi causa durante lo studio (<= 30 giorni dopo l'ultima dose del trattamento in studio) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Tumor assessments at end of Cycles 2, 4, 6 and 8 and every 3 cycles
thereafter |
Valutazioni tumorali alla fine dei cicli 2, 4, 6 e 8 e successivamente ogni 3 cicli |
|
E.5.2 | Secondary end point(s) |
The secondary activity outcome measures in all treated patients and in
patients with PI3K pathway abnormalities are the following:
- Objective tumor response as assessed by the investigator per modified RECIST v1.1
- Clinical benefit defined as PR, CR, or stable disease, lasting for at least
6 months (i.e., 26 weeks)
- Duration of confirmed objective response, defined as the time from first observation of an objective tumor response until first observation of disease progression as assessed by the investigator per modified RECIST
v1.1
- The mutational status of PIK3CA and the presence of complete loss of the PTEN as determined by IHC |
Le misurazioni degli obiettivi secondari di attività in tutti i pazienti e nei pazienti con anormalità nel pathway di PI3K sono:
- risposta tumorale obiettiva, valutata dallo sperimentatore mediante RECIST, versione 1.1 modificata
- beneficio clinico definito come PR, CR, o malattia stabile per almeno 6 mesi (es. 26 settimane)
- durata della risposta obiettiva confermata, definito come il tempo fra la prima osservazione della risposta tumorale obiettiva fino alla prima ossrvazione di progressione di malattia, valutata dallo sperimentatore mediante RECIST, versione 1.1
- stato mutazionale di PI3KCA e presenza di completa perdita di PTEN, determinata con immunoistochimica (IHC) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Tumor assessments at end of Cycles 2, 4, 6 and 8 and every 3 cycles
thereafter |
Valutazioni tumorali alla fine dei cicli 2, 4, 6 e 8 e successivamente ogni 3 cicli |
|
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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 66 |
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 |
Argentina |
Australia |
Brazil |
Canada |
Chile |
Hong Kong |
Israel |
Korea, Democratic People's Republic of |
Korea, Republic of |
Malaysia |
Mexico |
New Zealand |
Peru |
Russian Federation |
Singapore |
Taiwan |
Thailand |
Ukraine |
United States |
|
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
|
The end of the study is currently defined as the date on which the last patient has their last visit (LPLV). However, the Sponsor has the right to terminate this study at any timeprior to LPLV (see section 4.8 of study protocol for reasons for terminating the study prior to LPLV). |
Fine dello studio = data dell'ultima visita dell'ultimo pt(LPLV). Comunque lo Sponsor ha il diritto di interrompere lo studio in qualsiasi momento prima della LPLV (fare rif. a sez.4.8 del protocollo). |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 37 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 37 |
E.8.9.2 | In all countries concerned by the trial days | 0 |