Studie porovnávající biologickou dostupnost v ustáleném stavu injekčního letrozolu SIE a perorálního letrozolu u postmenopauzálních žen s časným karcinomem prsu pozitivním na hormonální receptory (SIE-1)
Otevřená, jednosekvenční studie k posouzení komparativní biologické dostupnosti v ustáleném stavu u čtvrtletně podávaného letrozolu SIE a jednou denně podávaného 2,5 mg perorálního letrozolu (Femara®) u postmenopauzálních žen léčených endokrinní terapií pro časný hormonálně receptor-pozitivní karcinom prsu. (SIE-1)
The study aims to compare the amount of the drug letrozole that gets into the bloodstream after multiple doses of the quarterly injection Letrozole SIE, versus multiple doses of the standard oral daily tablet of letrozole (Femara®), in women who have gone through menopause and have received treatment for hormone receptor-positive early breast cancer. Participants must have completed at least five years of hormone therapy with at least two of those years with letrozole before starting their participation in the study. Women who have completed four years of hormone therapy are also eligible if their doctor considers them at low risk of cancer returning.
Přehled studie
Postavení
Detailní popis
The primary objective of the study is to evaluate the steady-state comparative bioavailability of quarterly injectable Letrozole SIE compared to United States (US)-sourced oral Femara® in the US-sourced arm and of quarterly injectable Letrozole SIE compared to European Union (EU)-sourced oral Femara® in the EU-sourced arm, in post-menopausal women treated with endocrine therapy for hormone-receptor positive (HR+) early breast cancer (EBC). The study also aims to characterize the elimination phase of Letrozole SIE after multiple doses.
The study consists of four periods: Screening, Treatment Period 1 (TP1), Treatment Period 2 (TP2) and Extension Period. After the Screening Period, participants will be randomized to two different arms: US-sourced oral Femara® or EU-sourced oral Femara® for 14 days to achieve the steady-state concentrations of letrozole in TP1. After receiving the latest oral letrozole dose, participants from both arms will start TP2. In TP2, quarterly injectable Letrozole SIE will be administered to achieve steady-state. After TP2, a subset of participants (up to 60 participants, regardless of which study arm they belong to) will continue in the study for the assessment of the elimination phase of Letrozole SIE after multiple doses during the Extension Period.
It is estimated that approximately 120 subjects should be randomized.
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 1
Kontakty a umístění
Studijní kontakt
- Jméno: Clinical Operations. Laboratorios Farmacéuticos ROVI
- Telefonní číslo: +34913756230
- E-mail: departamento.medico@rovi.es
Studijní místa
-
-
California
-
Beverly Hills, California, Spojené státy, 90212
- Nábor
- Precision NextGen Oncology and Research Center (Investigational Site number USA-001)
-
-
Florida
-
Margate, Florida, Spojené státy, 33063
- Nábor
- D&H National Research Centers INC (Investigational Site number USA-002)
-
Port Orange, Florida, Spojené státy, 32127
- Nábor
- United Medical Research (Investigational Site number USA-005)
-
-
-
-
-
Belgrade, Srbsko, 11000
- Nábor
- Investigational Site number SRB-004
-
Belgrade, Srbsko, 11080
- Nábor
- Investigational Site number SRB-002
-
Kamenitz, Srbsko, 21204
- Nábor
- Investigational Site number SRB-001
-
Kragujevac, Srbsko, 34000
- Nábor
- Investigational Site number SRB-003
-
Niš, Srbsko, 18000
- Nábor
- Investigational Site number SRB-005
-
-
-
-
-
Alcorcón, Španělsko, 28922
- Nábor
- Hospital Universitario Fundación Alcorcón (Investigational Site number ESP-015)
-
Barcelona, Španělsko, 08023
- Nábor
- NEXT Oncology. Phase I Unit / IOB - Hospital Quironsalud Barcelona (Investigational Site number ESP-002)
-
Granada, Španělsko, 18014
- Nábor
- Hospital Universitario Virgen de las Nieves (Investigational Site number ESP-011)
-
Jaén, Španělsko, 23007
- Nábor
- Hospital Universitario de Jaén (HUJ) (Investigational Site number ESP-005)
-
León, Španělsko, 24071
- Nábor
- Complejo Asistencial Universitario de León - Hospital de León (Investigational Site number ESP-013)
-
Lleida, Španělsko, 25198
- Nábor
- Hospital Universitario Arnau de Vilanova de Lleida (Investigational Site number ESP-003)
-
Manresa, Španělsko, 08243
- Nábor
- Althaia Xarxa Assistencial Universitària de Manresa F.P (Investigational Site number ESP-012)
-
Murcia, Španělsko, 30120
- Nábor
- Hospital Clínico Universitario Virgen de la Arrixaca (Investigational Site number ESP-009)
-
Málaga, Španělsko, 29004
- Nábor
- Hospital Quirónsalud Málaga (Investigational Site number ESP-001)
-
Pozuelo de Alarcón, Španělsko, 28223
- Nábor
- NEXT Oncology Phase I Unit - Hospital Universitario Quironsalud Madrid (Investigational Site number ESP-008)
-
Reus, Španělsko, 43204
- Nábor
- Hospital Universitari Sant Joan de Reus (Investigational Site number ESP-004)
-
Sabadell, Španělsko, 08208
- Nábor
- Consorci Corporació Sanitària Parc Taulí - Hospital de Sabadell (Investigational Site number ESP-006)
-
Santiago de Compostela, Španělsko, 15705
- Nábor
- Hospital Clinico Universitario Santiago de Compostela (Investigational Site number ESP-007)
-
-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Women with weight of ≥50 kg and a Body Mass Index (BMI) ≥19 kg/m2 and ≤39 kg/m2
- Postmenopausal women.
- Women with confirmed diagnosis of HR+/HER2- or HR+/HER2+ early stage breast cancer who have completed at least 5 years of endocrine therapy, at least 2 years of which were with letrozole. Participants at a low risk of relapse, as assessed by the investigator, can also be eligible after completing 4 years of adjuvant endocrine therapy, at least 2 of which were with letrozole.
- Women in good health.
- Women who have undergone breast imaging per applicable guidelines (e.g., mammogram) within the last 12 months with no evidence of malignancy (documentation required), and if not done, must be willing to have 1 performed prior to baseline.
Exclusion Criteria:
- Presence of an uncontrolled, unstable, clinically significant medical condition.
- Have used estrogen or progesterone systemic or topical therapy, oral contraceptives, androgens, LH-releasing hormone analogs, prolactin inhibitors, or antiandrogens within 3 months prior to screening.
- Use of inducers or inhibitors of CYP3A4 and CYP2A6.
- Diagnosed with osteoporosis.
- Preexisting cardiovascular disease
- Positive result for hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, or HIV antibodies.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: US-sourced oral Femara®
|
US-sourced Femara® 2.5 mg/day oral for 14 days (treatment period 1) + quarterly injectable Letrozole SIE (treatment period 2) |
|
Experimentální: orální Femara® pocházející z EU
|
EU-sourced oral Femara® 2.5 mg/day for 14 days (treatment period 1) + quarterly injectable Letrozole SIE (treatment period 2) |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Area under the concentration-time curve within a dosing interval at Steady-State (SS AUCtau)
Časové okno: After multiple doses of Letrozole SIE until Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® on Day 14 TP1
|
Individual and mean area under the concentration-time curve within a dosing interval at steady-state |
After multiple doses of Letrozole SIE until Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® on Day 14 TP1
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Adverse Events
Časové okno: From the time of obtaining signed informed consent until the final follow-up visit on Day 281 (or Day 421 for the subset of participants in the Extension Period)
|
Incidence of adverse events (type, severity, seriousness, and relationship to study drug), including the incidence of treatment-emergent adverse events (TEAEs), the incidence of serious TEAEs, and the incidence of TEAEs leading to treatment discontinuation. |
From the time of obtaining signed informed consent until the final follow-up visit on Day 281 (or Day 421 for the subset of participants in the Extension Period)
|
|
Injection site reactions
Časové okno: At pre-dose and 1 hour after each Letrozole SIE administration in TP2
|
Incidence of injection site reactions |
At pre-dose and 1 hour after each Letrozole SIE administration in TP2
|
|
Injection-related pain score
Časové okno: From baseline TP2 to the follow-up visit on Day 281
|
Changes in injection-related pain score by numeric rating scale (NRS). The NRS evaluates the intensity of injection-related pain experienced at the time of Letrozole SIE administration. It is scored from 0 to 10 (0 meaning no pain and 10 meaning the worst possible pain). |
From baseline TP2 to the follow-up visit on Day 281
|
|
Bone mineral density (BMD) by dual energy x-ray absorptiometry (DXA)
Časové okno: From screening to Day 281 TP2
|
Changes in bone mineral density BMD by DXA |
From screening to Day 281 TP2
|
|
Average plasma drug concentration during a dosing interval at Steady-State (SS Cave)
Časové okno: After multiple doses of Letrozole SIE until Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® at Day 14 TP1
|
Individual and mean steady-state average plasma drug concentration during a dosing interval |
After multiple doses of Letrozole SIE until Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® at Day 14 TP1
|
|
Minimum drug concentration at steady-state (Cmin ss)
Časové okno: After multiple doses of Letrozole SIE until Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® at Day 14 TP1
|
Minimum drug concentration at steady-state |
After multiple doses of Letrozole SIE until Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® at Day 14 TP1
|
|
Maximum plasma concentration at steady-state (Cmax ss)
Časové okno: After multiple doses of Letrozole SIE at Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® at Day 14 TP1
|
Maximum plasma concentration at steady-state |
After multiple doses of Letrozole SIE at Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® at Day 14 TP1
|
|
Letrozole blood level percent fluctuation
Časové okno: After multiple doses of Letrozole SIE at Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® at Day 14 TP1
|
Individual and mean letrozole blood percent fluctuation |
After multiple doses of Letrozole SIE at Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® at Day 14 TP1
|
|
Time to peak observed concentration (Tmax)
Časové okno: After multiple doses of Letrozole SIE until Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® at Day 14 TP1
|
Time to peak observed concentration |
After multiple doses of Letrozole SIE until Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® at Day 14 TP1
|
|
Steady-State (SS)
Časové okno: After multiple doses of Letrozole SIE until Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® at Day 14 TP1
|
Characterization of the steady-state |
After multiple doses of Letrozole SIE until Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® at Day 14 TP1
|
|
Terminal rate constant (λz)
Časové okno: After multiple doses of Letrozole SIE in TP2 until Day 421 in the Extension Period
|
Individual and mean Terminal rate constant (λz) after multiple doses of Letrozole SIE in the subset of participants in the Extension Period |
After multiple doses of Letrozole SIE in TP2 until Day 421 in the Extension Period
|
|
Terminal half-life (t1/2)
Časové okno: After multiple doses of Letrozole SIE in TP2 until Day 421 in the Extension Period
|
Individual and mean Terminal half-life after multiple doses of Letrozole SIE in the subset of participants in the Extension Period |
After multiple doses of Letrozole SIE in TP2 until Day 421 in the Extension Period
|
|
Area under the curve extrapolated to infinity (AUC∞)
Časové okno: After multiple doses of Letrozole SIE in TP2 until Day 421 in the Extension Period
|
Individual and mean Area under the curve extrapolated to infinity after multiple doses of Letrozole SIE in the subset of participants in the Extension Period |
After multiple doses of Letrozole SIE in TP2 until Day 421 in the Extension Period
|
|
Area under the curve that is extrapolated (AUCextrap)
Časové okno: After multiple doses of Letrozole SIE in TP2 until Day 421 in the Extension Period
|
Percentage of area under the curve that is extrapolated after multiple doses of Letrozole SIE in the subset of participants in the Extension Period |
After multiple doses of Letrozole SIE in TP2 until Day 421 in the Extension Period
|
Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Hormone supression
Časové okno: From screening to the final follow-up visit on Day 281 (or Day 421 for the subset of participants in the Extension Period)
|
Analysis of letrozole exposure and hormone suppression measuring the sex hormone estrone (E1), sulfate estrone (SE1), and estradiol (E2) plasma levels. |
From screening to the final follow-up visit on Day 281 (or Day 421 for the subset of participants in the Extension Period)
|
|
CYP2A6 genotyping
Časové okno: From screening to final follow-up visit Day 281 (or Day 421 for the subset of participants in the Extension Period)
|
Proportion of participants in each CYP2A6 metabolizer phenotype category (normal, intermediate, slow) |
From screening to final follow-up visit Day 281 (or Day 421 for the subset of participants in the Extension Period)
|
Spolupracovníci a vyšetřovatelé
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- ROV-SIE-2025-01
- 2025-523269-31-00 (Ctis)
- 2025 (Grant/smlouva NIH USA)
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .