A Study to Compare the Steady-State Bioavailability of Injectable Letrozole SIE and Oral Letrozole in Post-Menopausal Women With Hormone Receptor Positive Early Breast Cancer (SIE-1)

September 10, 2026 updated by: Rovi Pharmaceuticals Laboratories

An Open-Label, One-Sequence Study to Evaluate the Steady-State Comparative Bioavailability of Quarterly Letrozole SIE and Once Daily 2.5 mg Oral Letrozole (Femara®) in Post-Menopausal Women Treated With Endocrine Therapy for Hormone Receptor-Positive Early Breast Cancer. (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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Serbia
      • Belgrade, Serbia, 11000
        • Recruiting
        • Investigational Site number SRB-004
      • Belgrade, Serbia, 11080
        • Recruiting
        • Investigational Site number SRB-002
      • Kamenitz, Serbia, 21204
        • Recruiting
        • Investigational Site number SRB-001
      • Kragujevac, Serbia, 34000
        • Recruiting
        • Investigational Site number SRB-003
      • Niš, Serbia, 18000
        • Recruiting
        • Investigational Site number SRB-005
  • Spain
      • Alcorcón, Spain, 28922
        • Recruiting
        • Hospital Universitario Fundación Alcorcón (Investigational Site number ESP-015)
      • Barcelona, Spain, 08023
        • Recruiting
        • NEXT Oncology. Phase I Unit / IOB - Hospital Quironsalud Barcelona (Investigational Site number ESP-002)
      • Granada, Spain, 18014
        • Recruiting
        • Hospital Universitario Virgen de las Nieves (Investigational Site number ESP-011)
      • León, Spain, 24071
        • Recruiting
        • Complejo Asistencial Universitario de León - Hospital de León (Investigational Site number ESP-013)
      • Lleida, Spain, 25198
        • Recruiting
        • Hospital Universitario Arnau de Vilanova de Lleida (Investigational Site number ESP-003)
      • Manresa, Spain, 08243
        • Recruiting
        • Althaia Xarxa Assistencial Universitària de Manresa F.P (Investigational Site number ESP-012)
      • Murcia, Spain, 30120
        • Recruiting
        • Hospital Clínico Universitario Virgen de la Arrixaca (Investigational Site number ESP-009)
      • Málaga, Spain, 29004
        • Recruiting
        • Hospital Quirónsalud Málaga (Investigational Site number ESP-001)
      • Pozuelo de Alarcón, Spain, 28223
        • Recruiting
        • NEXT Oncology Phase I Unit - Hospital Universitario Quironsalud Madrid (Investigational Site number ESP-008)
      • Sabadell, Spain, 08208
        • Recruiting
        • Consorci Corporació Sanitària Parc Taulí - Hospital de Sabadell (Investigational Site number ESP-006)
      • Santiago de Compostela, Spain, 15705
        • Recruiting
        • Hospital Clinico Universitario Santiago de Compostela (Investigational Site number ESP-007)
  • United States
    • California
      • Beverly Hills, California, United States, 90212
        • Recruiting
        • Precision NextGen Oncology and Research Center (Investigational Site number USA-001)
    • Florida
      • Margate, Florida, United States, 33063
        • Recruiting
        • D&H National Research Centers INC (Investigational Site number USA-002)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: US-sourced oral Femara®
Drug: US-sourced oral Femara® + Letrozole SIE
US-sourced Femara® 2.5 mg/day oral for 14 days (treatment period 1) + quarterly injectable Letrozole SIE (treatment period 2)
Experimental: EU-sourced oral Femara®
Drug: EU sourced oral Femara® + Letrozole SIE
EU-sourced oral Femara® 2.5 mg/day for 14 days (treatment period 1) + quarterly injectable Letrozole SIE (treatment period 2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the concentration-time curve within a dosing interval at Steady-State (SS AUCtau)
Time Frame: 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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Events
Time Frame: 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
Time Frame: 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
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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∞)
Time Frame: 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)
Time Frame: 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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hormone supression
Time Frame: 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
Time Frame: 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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rovi Pharmaceuticals Laboratories

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 8, 2026

Primary Completion (Estimated)

May 1, 2028

Study Completion (Estimated)

October 1, 2028

Study Registration Dates

First Submitted

January 22, 2026

First Submitted That Met QC Criteria

February 3, 2026

First Posted (Actual)

February 10, 2026

Study Record Updates

Last Update Posted (Actual)

September 11, 2026

Last Update Submitted That Met QC Criteria

September 10, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ROV-SIE-2025-01
  • 2025 (U.S. NIH Grant/Contract: Faculty of Social Sciences Scientific Grant at the University of Gdańsk)
  • 2025-523269-31-00 (Ctis)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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