E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Breast cancer |
Carcinoma mammario |
|
E.1.1.1 | Medical condition in easily understood language |
Breast cancer |
Carcinoma mammario |
|
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 | PT |
E.1.2 | Classification code | 10057654 |
E.1.2 | Term | Breast cancer female |
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 increase (a 50% increase) in serum Estradiol levels after 3-month estradiol treatment. |
Valutare l’aumento (aumento del 50%) dei livelli sierici di estradiolo dopo 3 mesi di trattamento con estradiolo. |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate patient-reported outcomes (PRO) in terms of symptoms related to endocrine treatment and two global quality of life (QoL) indicators.
• To evaluate the change in the biochemical marker of bone turnover modification C-telopeptide (C-terminal telopeptide of the 1 chain of type I collagen (CTX)), after 3-month estradiol treatment.
• To evaluate breast cancer related free survival (BCRS), disease free survival (DFS), and overall survival (OS).
• To compare the results of this study to the results of our previous study on 3-month letrozole therapy free interval. |
• valutare la Qualità di Vita in relazione alla salute e agli effetti indesiderati degli estrogeni.
• valutare eventuali variazioni del marcatore osseo C-telopeptide (telopeptide C-terminale del collagene di tipo I (CTx)) dopo 3 mesi di trattamento con estradiolo
• valutare la sopravvivenza libera da malattia mammaria, la sopravvivenza libera da malattia e la sopravvivenza globale
confrontare i risultati di questo studio con quelli di uno studio precedente che prevedeva assunzione intermittente di Letrozolo. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Postmenopausal women with operable breast cancer
- Patient with diagnosis of histological proven breast cancer (pT1, pT2, or pT3, N sentinel negative, pN0(either i- or i+); M0.
- Diagnosis of hormone receptor positive tumors. (ER and/or PgR must be greater than or equal to 10%) |
Pazienti in postmenopausa con diagnosi di carcinoma mammario operabile
-Pazienti con diagnosi di carcinoma mammario istologicamente confermato (pT1, pT2, o pT3, Nsentinelnegative, pN0 [sia i-o i+], M0)
-Diagnosi di carcinoma mammario endocrinoresponsivo (ER e/o PgR≥10%) |
|
E.4 | Principal exclusion criteria |
Patients who are premenopausal
- Patients with locally advanced disease (pN1, pN2, pN3) or distant metastatic disease
- Patients with bilateral invasive breast cancer
- Patients with positive final margins (referring to only DCIS and invasive cancer, not LCIS).
- Patients with a history of prior ipsilateral or contralateral invasive breast cancer.
- Patients with previous or concomitant malignancy EXCEPT adequately treated (basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, contra- or ipsilateral in situ breast carcinoma).
- Patients who have received prior therapy for breast cancer including prior irradiation, adjuvant or neoadjuvant chemotherapy or endocrine therapy.
- Patients who were taking tamoxifen or other SERM (e.g. Raloxifene) or hormone replacement therapy (HRT) within one year prior to their breast cancer diagnosis. |
Pazienti in premenopausa
-Pazienti con carcinoma mammario localmente avanzato (pN1, pN2, pN3) o metastatico
-Pazienti con carcinoma mammario bilaterale alla diagnosi
-Pazienti con margini tissutali positivi per DCIS o carcinoma infiltrante dopo l’intervento chirurgico
-Pazienti con anamnesi positiva per carcinoma mammario infiltrante ipsilaterale o controlaterale
-Pazienti con pregressa o concomitante neoplasia, eccetto i tumori baso-spinocellulari, il carcinoma in situ della cervice uterina o della vescica, i carcinomi mammari in situ ipsi-controlaterali
-Pazienti che hanno ricevuto una terapia endocrina neoadiuvante
-Pazienti che abbiano assunto tamoxifene o un altro SERM (eccetto raloxifene), o altri trattamenti ormonali steroidei nell’ultimo anno prima della diagnosi di carcinoma mammario |
|
E.5 End points |
E.5.1 | Primary end point(s) |
serum Estradiol levels after 3-month estradiol treatment. |
livelli sierici di estradiolo dopo 3 mesi di trattamento con estradiolo. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
at baseline and after 3 months of treatment |
prima dell'inizio ed al termine di 3 mesi di trattamento |
|
E.5.2 | Secondary end point(s) |
• patient-reported outcomes (PRO) in terms of symptoms related to endocrine treatment and two global quality of life (QoL) indicators.
• variations of biochemical marker of bone turnover modification C-telopeptide (C-terminal telopeptide of the 1 chain of type I collagen (CTX)), after 3-month estradiol treatment.
• breast cancer related free survival (BCRS), disease free survival (DFS), and overall survival (OS). |
•Qualità di Vita in relazione alla salute e agli effetti indesiderati degli estrogeni.
•Variazioni del marcatore osseo C-telopeptide (telopeptide C-terminale del collagene di tipo I (CTx)
sopravvivenza libera da malattia mammaria, la sopravvivenza libera da malattia e la sopravvivenza globale |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
For Quality of Life: 24 months
For C-tepoleptide marker evaluation: 15 months
For BCRS, DFS, OS evaluation: ongoing |
Per la Qualità di Vita: 24 mesi
Per la valutazione del marcatore C-telopeptide: 15 mesi
Per la valutazione di BCRS, DFS, OS: ongoing |
|
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 | No |
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 | 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 | 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 |
- Stesso farmaco ad altro dosaggio |
- same IMP used at different dosage |
|
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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 | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |