Een studie om de steady-state biologische beschikbaarheid van injecteerbaar letrozol SIE en oraal letrozol te vergelijken bij postmenopauzale vrouwen met hormoonreceptorpositieve vroege borstkanker (SIE-1)
Een open-label, één-sequentie onderzoek om de steady-state vergelijkende biologische beschikbaarheid te evalueren van driemaandelijks letrozol SIE en eenmaal daags 2,5 mg oraal letrozol (Femara®) bij postmenopauzale vrouwen behandeld met endocriene therapie voor hormoonreceptor-positieve vroege borstkanker. (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.
Studie Overzicht
Toestand
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Geschat)
Fase
- Fase 1
Contacten en locaties
Studiecontact
- Naam: Clinical Operations. Laboratorios Farmacéuticos ROVI
- Telefoonnummer: +34913756230
- E-mail: departamento.medico@rovi.es
Studie Locaties
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Belgrade, Servië, 11000
- Werving
- Investigational Site number SRB-004
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Belgrade, Servië, 11080
- Werving
- Investigational Site number SRB-002
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Kamenitz, Servië, 21204
- Werving
- Investigational Site number SRB-001
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Kragujevac, Servië, 34000
- Werving
- Investigational Site number SRB-003
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Niš, Servië, 18000
- Werving
- Investigational Site number SRB-005
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Alcorcón, Spanje, 28922
- Werving
- Hospital Universitario Fundación Alcorcón (Investigational Site number ESP-015)
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Barcelona, Spanje, 08023
- Werving
- NEXT Oncology. Phase I Unit / IOB - Hospital Quironsalud Barcelona (Investigational Site number ESP-002)
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Granada, Spanje, 18014
- Werving
- Hospital Universitario Virgen de las Nieves (Investigational Site number ESP-011)
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Jaén, Spanje, 23007
- Werving
- Hospital Universitario de Jaén (HUJ) (Investigational Site number ESP-005)
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León, Spanje, 24071
- Werving
- Complejo Asistencial Universitario de León - Hospital de León (Investigational Site number ESP-013)
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Lleida, Spanje, 25198
- Werving
- Hospital Universitario Arnau de Vilanova de Lleida (Investigational Site number ESP-003)
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Manresa, Spanje, 08243
- Werving
- Althaia Xarxa Assistencial Universitària de Manresa F.P (Investigational Site number ESP-012)
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Murcia, Spanje, 30120
- Werving
- Hospital Clínico Universitario Virgen de la Arrixaca (Investigational Site number ESP-009)
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Málaga, Spanje, 29004
- Werving
- Hospital Quirónsalud Málaga (Investigational Site number ESP-001)
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Pozuelo de Alarcón, Spanje, 28223
- Werving
- NEXT Oncology Phase I Unit - Hospital Universitario Quironsalud Madrid (Investigational Site number ESP-008)
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Reus, Spanje, 43204
- Werving
- Hospital Universitari Sant Joan de Reus (Investigational Site number ESP-004)
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Sabadell, Spanje, 08208
- Werving
- Consorci Corporació Sanitària Parc Taulí - Hospital de Sabadell (Investigational Site number ESP-006)
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Santiago de Compostela, Spanje, 15705
- Werving
- Hospital Clinico Universitario Santiago de Compostela (Investigational Site number ESP-007)
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California
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Beverly Hills, California, Verenigde Staten, 90212
- Werving
- Precision NextGen Oncology and Research Center (Investigational Site number USA-001)
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Florida
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Margate, Florida, Verenigde Staten, 33063
- Werving
- D&H National Research Centers INC (Investigational Site number USA-002)
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Port Orange, Florida, Verenigde Staten, 32127
- Werving
- United Medical Research (Investigational Site number USA-005)
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
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Experimenteel: US-sourced oral Femara®
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US-sourced Femara® 2.5 mg/day oral for 14 days (treatment period 1) + quarterly injectable Letrozole SIE (treatment period 2) |
|
Experimenteel: EU-gebaseerde orale Femara®
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EU-sourced oral Femara® 2.5 mg/day for 14 days (treatment period 1) + quarterly injectable Letrozole SIE (treatment period 2) |
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Area under the concentration-time curve within a dosing interval at Steady-State (SS AUCtau)
Tijdsspanne: 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
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Adverse Events
Tijdsspanne: 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)
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Injection site reactions
Tijdsspanne: 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
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Injection-related pain score
Tijdsspanne: 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
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|
Bone mineral density (BMD) by dual energy x-ray absorptiometry (DXA)
Tijdsspanne: From screening to Day 281 TP2
|
Changes in bone mineral density BMD by DXA |
From screening to Day 281 TP2
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Average plasma drug concentration during a dosing interval at Steady-State (SS Cave)
Tijdsspanne: 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)
Tijdsspanne: 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
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Maximum plasma concentration at steady-state (Cmax ss)
Tijdsspanne: 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
Tijdsspanne: 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
|
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Time to peak observed concentration (Tmax)
Tijdsspanne: 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
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Steady-State (SS)
Tijdsspanne: 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
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Terminal rate constant (λz)
Tijdsspanne: After multiple doses of Letrozole SIE in TP2 until Day 421 in the Extension Period
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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
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Terminal half-life (t1/2)
Tijdsspanne: 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∞)
Tijdsspanne: 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)
Tijdsspanne: 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
|
Andere uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Hormone supression
Tijdsspanne: 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)
|
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CYP2A6 genotyping
Tijdsspanne: 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)
|
Medewerkers en onderzoekers
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- ROV-SIE-2025-01
- 2025-523269-31-00 (Ctis)
- 2025 (Subsidie/contract van de Amerikaanse NIH)
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
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