E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pre- and postmenopausal women who are receiving adjuvant endocrine treatment (LH-RH analogue plus Tamoxifene or Aromatase Inhibitor, Tamoxifene alone, Aromatase Inhibitor alone) for early breast cancer. |
Pazienti in pre- e postmenopausa in trattamento endocrino per carcinoma della mammella, sintomatiche per disturbi uro-genitali refrattari a trattamento con lubrificanti topici. |
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E.1.1.1 | Medical condition in easily understood language |
Endocrine treatments for breast cancer therapy determine a drastic reduction of estrogens that leads to, in many women, a progressive urogenital atrophy. |
I trattamenti endocrini per carcinoma della mammella causano una riduzione drastica degli estrogeni con atrofia urogenitale in molte pazienti. |
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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 | 10006283 |
E.1.2 | Term | Breast neoplasm malignant female |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
The aim of this study is to evaluate the safety and the efficacy of treatment with low doses of vaginal estrogens in pre and post menopausal patients with previous diagnosis of breast cancer and urogenital symptoms related to the adjuvant hormonal therapy |
Lo scopo di questo studio è di valutare la sicurezza e l'efficacia del trattamento con basse dosi di estrogeni vaginali nelle pazienti in pre-e post-menopausa con precedente diagnosi di carcinoma della mammella e sintomi urogenitali correlati alla terapia ormonale adiuvante |
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E.2.2 | Secondary objectives of the trial |
The evaluation of quality of life and the Efficacy of Vagifem in terms of vulvovaginal epithelial maturation during treatment |
La valutazione della Qualità della vita e l’efficacia del trattamento sperimentale sulla maturazione dell’epitelio vulvovaginale. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients mast have histologically proven primary breast cancer;
• Age 18-70 years;
• Immunohistochemical evaluation of ER, PgR, HER2, is mandatory;
• ER and/or PgR must be ≥ 10%
• Postmenopausal level of serum estrogen (< 5 – 30 pg/ml );
• Patients must have had proper surgery for primary breast cancer;
• Patients should be treated with hormone therapy (Tamoxifene, letrozole, anastrozole, exemestane and/or LH-RH analogue);
• Urogenital symptoms (Vaginal dryness, Vaginal atrophy, Dyspareunia, Decreased libido, Urinary urgency/frequency ); patients must be refractory to local non-hormonal treatments for urogenital symptoms;
• No evidence of distant metastatic disease;
• ECOG performance status <2;
• No significant co-morbidities ( > grade 2);
Signed informed consent. |
• Pazienti con diagnosi istologica di carcinoma mammario;
• Età tra i 18 e i 70 anni;
• E’ obbligatoria la valutazione immunoistochimica di ER, PgR, HER2;
• ER e/o PgR ≥ 10%;
• Le pazienti devono avere dei livelli sierici di estrogeno compatibili con menopausa (< 5 – 30 pg/ml);
• Le pazienti devono essere state sottoposte a chirurgia adeguata;
• Le pazienti devono essere in trattamento adiuvante endocrino (Tamoxifene, letrozole, anastrozole, exemestane e/o LH-RH analogue);
• Le pazienti devono lamentare sintomi urogenitali (secchezza vaginale, atrofia, dispareunia, riduzione della libido) refrattari a trattamenti non-ormonali per sintomi urogenitali;
• Nessuna evidenza di metastasi;
• ECOG performance status<2;
• Nessuna comorbidità significativa (grado>2);
• Le pazienti devono firmare il Consenso Informato ai fini della partecipazione allo studio. |
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E.4 | Principal exclusion criteria |
• Patients with previous or concomitant malignancy;
• Patients who exceed the postmenopausal estradiol serum level of 30 pg/ml at baseline;
• Uncontrolled undercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements;
• Patients who have received prior therapy for breast cancer;
• Patients who have received endometrial biopsy; |
• Pazienti con altre neoplasie precedenti o concomitanti;
• Pazienti con valori basali di estradiolo superiori o uguali a 30 pg/ml;
• Patologie scompensate come scompenso cardiaco, angina pectoris, aritmie cardiache, patologie psichiatriche che limitino la compliance al trattamento, infezioni attive in atto;
• Pazienti che hanno già ricevuto trattamenti per un precedente carcinoma mammario;
• Pazienti già sottoposte a biopsie endometriali; |
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E.5 End points |
E.5.1 | Primary end point(s) |
maintenance of serum estradiol levels in postmenopausal range. |
mantenimento di livelli sierici di estradiolo in range postmenopausali. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at the baseline, at the 8th day of treatment and at the 28th day |
al basale, al giorno 8 di trattamento e al giorno 28 di trattamento |
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E.5.2 | Secondary end point(s) |
Targeted Quality of Life (sexual functioning) of patients during treatment.
- Efficacy of Vagifem in terms of vulvovaginal epithelial maturation during treatment.
- Estradiol serum levels during the study period and follow up. |
Qualità della vita delle pazienti durante il trattamento.
- Efficacia di Vagifem in termini di maturazione dell’epitelio vulvovaginale durante il trattamento.
- Livello di estradiolo sierico durante il periodo di studio e follow up |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At baseline, Day 28, 6th month, yearly (from year 1 to year 5) |
Al basale, giorno 28, 6 mese, annualmente fino a 5 anni |
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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 | 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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 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
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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 | 6 |
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 | 6 |
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 |