Ovarian Suppression Evaluating Subcutaneous Leuprolide Acetate in Breast Cancer (OVELIA)

January 9, 2026 updated by: Tolmar Inc.

Phase 3,Single Arm,Open-Label Study Evaluating Ovarian Suppression Following 3 Month Leuprolide Acetate For Injectable Suspension (TOL2506) in Combination With Endocrine Therapy in Premenopausal Subjects With Hormone-Receptor-Positive (HR+),Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer

This is a phase 3, single arm, open-label study evaluating the effectiveness of TOL2506 to suppress ovarian function in premenopausal women with HR+, HER2-negative breast cancer. The study will also aim to assess the safety of TOL2506 in men with HR+, HER2-negative breast cancer. The Screening Period will be conducted in two parts: 1) an abbreviated, initial screening where premenopausal status will be determined prior to neoadjuvant or adjuvant chemotherapy (if planned) and 2) the full screening assessment conducted after neoadjuvant or adjuvant chemotherapy (or for subjects who enter the study without having received chemotherapy). Following the Screening Period, eligible subjects will enter into the 48 week Treatment Period in 1 of 2 groups: those who will receive tamoxifen concurrently with TOL2506 or those who will initiate therapy with an AI (letrozole, anastrozole, or exemestane) beginning 6 weeks after the first administration of TOL2506, upon confirmation that estradiol (E2) levels of < 20 pg/mL (testosterone levels < 50 ng/dL in males) have been achieved. After Week 12, subjects will be allowed to switch from receiving an AI to receiving tamoxifen or from tamoxifen to AI at the discretion of the Investigator. However, a switch is not permitted 28 days prior to a dosing visit (eg, Week 24, 36, and 48 where a pre-dose blood sample for PK and PD analysis will be drawn). At the end of the Treatment Period, upon completion of the End of Study Visit (Visit 9, Week 48) subjects may be eligible to participate in a Safety Extension Study under a separate Protocol.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

250

Phase

  • Phase 3

Contacts and Locations

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

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C118AAT
        • Hospital Alemán
      • CABA, Argentina, C1125ABD
        • Fundacion CENIT
      • Córdoba, Argentina, X5000JHQ
        • Sanatorio Allende- Sede Nueva Cordoba
    • Buenos Aires F.D.
      • Buenos Aires, Buenos Aires F.D., Argentina, C1480AEB
        • Hospital Británico de Buenos Aires
    • Córdoba Province
      • Córdoba, Córdoba Province, Argentina, 5000
        • Instituto Oncologico de Cordoba (IONC)
      • Río Cuarto, Córdoba Province, Argentina, 5800
        • Centro Privado de RMI Rio Cuarto
    • Santa Fe Province
      • Rosario, Santa Fe Province, Argentina, S2000DEJ
        • Instituto Medico de la Fundacion Estudios Clinicos
      • Rosario, Santa Fe Province, Argentina, S2000KDS
        • Hospital Provincial del Centenario
  • Brazil
      • Porto Alegre, Brazil, 90020-090
        • Irmamandade de Santa Casa de Misericordia de Porto Alegre
      • Rio de Janeiro, Brazil, 22775-001
        • Instituto de Educacao, Pesquisa e Gestao em Saude
    • Ceará
      • Fortaleza, Ceará, Brazil, 60335-480
        • Centro Regional Integrado de Oncologia
      • Fortaleza, Ceará, Brazil, 60135-237
        • Oncocentro Serviços Médicos e Hospitalares Ltda
    • Estado de Bahia
      • Salvador, Estado de Bahia, Brazil, 41253-190
        • Hospital Sao Rafael
    • Goiás
      • Goiânia, Goiás, Brazil, 74605-070
        • Hospital Araujo Jorge
    • Mato Grosso do Sul
      • Campo Grande, Mato Grosso do Sul, Brazil, 79002-061
        • Onconeo
    • Paraná
      • Londrina, Paraná, Brazil, 86015-520
        • Hospital do Cancer de Londrina
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
        • Uniao Brasileira de Educacao e Assistencia
    • Rondônia
      • Porto Velho, Rondônia, Brazil, 76834-899
        • Hospital de Amor Amazonia
    • São Paulo
      • Barretos, São Paulo, Brazil, 14784-400
        • Fundacao Pio XII
      • Santo André, São Paulo, Brazil, 09060-650
        • Centro de Estudos e Pesquisas de Hematologia e Oncologia da Faculdade de Medicina do ABC
      • São Paulo, São Paulo, Brazil, 01317-001
        • Clinica de Pesquisa E Centro de Estudos Em Oncologia Ginecologica E Mamaria
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1Z5
        • Princess Margaret Cancer Centre
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Odette Cancer Centre Clinical Research Program
  • India
    • Andhra Pradesh
      • Vijayawada, Andhra Pradesh, India, 520002
        • HCG City Cancer Centre
      • Visakhapatnam, Andhra Pradesh, India, 530040
        • Apollo Hospitals
      • Visakhapatnam, Andhra Pradesh, India, 530040
        • HCG Cancer Centre
    • Gujarat
      • Ahmedabad, Gujarat, India, 380054
        • Hemato Oncology Clinic Ahmedabad Pvt. Ltd.
      • Surat, Gujarat, India, 395002
        • Unique Hospital Multispecialty & Research Institute
    • Karnataka
      • Bengaluru, Karnataka, India, 560027
        • SRV AGADI Hospital and Research Centre
      • Bengaluru, Karnataka, India, 560072
        • Oncoville Cancer Hospital and Research Center
      • Mysore, Karnataka, India, 570001
        • Mysore Medical College and Research Institute
    • Maharashtra
      • Nagpur, Maharashtra, India, 440001
        • KIMS-Kingsway Hospitals, SPANV Medisearch Lifesciences
      • Nashik, Maharashtra, India, 42202
        • HCG Manavata Cancer Centre
      • Pune, Maharashtra, India, 412105
        • Indrayani Hospital and Cancer Institute
    • Tamil Nadu
      • Erode, Tamil Nadu, India, 638012
        • Erode Cancer Centre Private Ltd.
    • Telangana
      • Hyderabad, Telangana, India, 500096
        • Apollo Cancer Hospitals
    • Uttar Pradesh
      • Varanasi, Uttar Pradesh, India, 221004
        • Swami Harshankaranand Ji Hospital & Research Centre
  • Mexico
      • Mexico City, Mexico, 03339
        • Clinica EMA
      • Veracruz, Mexico, 91900
        • FAICIC S. de R.L. de C.V.
    • Mexico City
      • Mexico City, Mexico City, Mexico, 07300
        • Amiisto Atencion Medica Integral, Investigacion Y Terapia Oncologica S.A De C.V.
    • Querétaro
      • San Juan del Río, Querétaro, Mexico, 76800
        • Unidad de Medicina Especializada SMA
  • Puerto Rico
      • San Juan, Puerto Rico, 00927
        • FDI Clinical Research
  • United States
    • California
      • Greenbrae, California, United States, 94904
        • Marin Cancer Care, Inc
    • Colorado
      • Parker, Colorado, United States, 80138
        • Cypress Hematology and Oncology
    • Illinois
      • Chicago, Illinois, United States, 60608
        • Mount Sinai Hospital
    • Kentucky
      • Louisville, Kentucky, United States, 40207
        • Baptist Health Louisville
    • Maryland
      • Glenn Dale, Maryland, United States, 20769
        • Maryland Oncology Hematology, P.A.
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Nebraska Cancer Specialists
    • New York
      • The Bronx, New York, United States, 10461
        • Montefiore - Einstein Center for Cancer Care at Montefiore Medical Park
    • Ohio
      • Cincinnati, Ohio, United States, 45211
        • Oncology Hematology Care Clinical Trials
    • Pennsylvania
      • Wynnewood, Pennsylvania, United States, 19096
        • Lankenau Medical Center
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • Tennessee Oncology, PLLC
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology, PLLC
    • Texas
      • Austin, Texas, United States, 78731
        • Texas Oncology-Austin
      • Dallas, Texas, United States, 75231
        • Texas Oncology- Dallas Presbyterian Hospital
      • New Braunfels, Texas, United States, 78130
        • Texas Oncology- San Antonio
      • Tyler, Texas, United States, 75702
        • Texas Oncology- Northeast Texas
      • Webster, Texas, United States, 77598
        • Texas Oncology- Deke Slayton Cancer Center
    • Washington
      • Seattle, Washington, United States, 98109
        • Seattle Cancer Center Alliance

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

18 years to 49 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Female

  1. Able to understand the investigational nature of this study and provide written informed consent prior to the participation in the trial
  2. Age 18 to 49, inclusive
  3. Diagnosis of Stage I, II, or III HR+, HER2-negative breast cancer (ER>1% and/or, PR>1%, HER2-negative per ASCO CAP guidelines)
  4. Is a candidate for endocrine therapy + ovarian suppression LH > 4 IU/L within 28 days prior to Day 1

  5. Is premenopausal as defined by:

    • E2 > 30 pg/mL
    • follicle stimulating hormone (FSH) < 40 IU/L
    • regular menses (eg, menstrual cycle length of 21 to 35 days) Note: premenopausal status must be determined before neo/adjuvant chemotherapy in patients for which it is planned or prior to Day 1 in patients who did not have prior chemotherapy. If premenopausal status was not determined prior to chemotherapy, E2 and FSH must meet the above criteria when measured 2 weeks or more after the end of the final cycle of chemotherapy.

Exclusion Criteria:

  1. Body mass index (BMI) < 18.00 kg/m2 or > 35.00 kg/m2
  2. Breastfeeding
  3. Life expectancy < 12 months
  4. Eastern Cooperative Oncology Group (ECOG) performance status ≥ 3

  5. Unacceptable hepatic function as determined by any of the following:

    1. Alanine aminotransferase (ALT) ≥ 2X upper limit of normal (ULN)
    2. Aspartate aminotransferase (AST) ≥ 2X ULN
    3. Bilirubin ≥ 2X ULN
    4. Alkaline phosphatase ≥ 2X ULN
    5. Severe hepatic impairment (Child-Pugh Class C)

  6. Unacceptable renal function as determined by any of the following:

    1. Creatinine ≥ 3X ULN
    2. Creatinine clearance ≤ 30 mL/minute
    3. Creatinine clearance ≤ 60 mL/minute in subjects with bone density 1.5 standard deviations below the young adult normal mean

  7. History of significantly abnormal ECG or screening 12-lead ECG demonstrating any of the following:

    1. HR > 100 BPM
    2. QRS > 120 msec
    3. QTc > 450 msec
    4. PR > 220 msec
  8. Prior (within 28 days prior to Day 1) and/or concomitant use of medications known to prolong the QT/QTc interval
  9. Prior use of tamoxifen, other SERMs (eg, raloxifene) or antagonists (eg, fulvestrant), aromatase inhibitor, mammalian target of rapamycin (mTOR) inhibitors, or hormone replacement therapy within 3 months before breast cancer diagnosis
  10. Concomitant use of anticancer mediations other than those specified for use by the protocol
  11. Prior neoadjuvant or adjuvant endocrine therapy since diagnosis of breast cancer
  12. History of treatment for osteopenia/osteoporosis or baseline bone mineral density Z-score ≤ -2.0
  13. Prior (within 6 months prior to Day 1) or current use of drugs known to increase bone mineral density (ie, bisphosphonates, denosumab, teriparatide, abaloparatide, romosozumab) or use of supplements known to increase bone mineral density (ie, calcitonin, fluoride, strontium) within 28 days prior to Day 1
  14. Low trauma fracture(s) occurring within 12 months prior to subject's first visit (defined as a fracture that results from a fall from a standing height or less, excluding fingers, toes, face and skull)
  15. Conditions that preclude bone mineral density measurement (lumbar spine/bilateral hip surgery with hardware in place, abdominal clips, umbilical ring [not willing to remove] or weight that exceeds the DEXA machine limitation)
  16. Any other medical condition or serious illness, presence of a second malignancy under current treatment or follow-up, or the presence of clinically significant findings on the physical exam, laboratory testing, medical history (including conditions that may be associated with low bone mass), that in the opinion of the Investigator may interfere with trial conduct, subject safety, or interpretation of study results
  17. Already receiving and/or previously received GnRH analogs within 1 year before breast cancer diagnosis
  18. Psychiatric, addictive, or other disorders that would preclude study compliance

  19. Use of medications that may impact subject safety and/or affect the PK of the drug and hormonal assessments including but not limited to:

    1. Oral or transdermal hormonal therapy within 30 days prior to subject's first visit
    2. Estrogen, progesterone, or androgens within 30 days prior to subject's first visit
    3. Hormonal contraceptives within 30 days prior to subject's first visit
    4. Medications known to result in clinically important decreases in bone mass taken within 6 months prior to subject's first visit
  20. Known hypersensitivity, idiosyncratic, or allergic reactions to GnRH, GnRH agonist/analogs or to any of the components of the IP
  21. Sexually active with a male partner and not willing to use non-hormonal contraceptive methods throughout the study
  22. Is of childbearing potential with a positive serum pregnancy test at Screening or urine pregnancy test at Day 1
  23. Exposure to any investigational agent within 30 days prior to the first dose of TOL2506

See contact information to obtain inclusion/exclusion criteria for males

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active Comparator: TOL2506
TOL2506 in combinatination with standard endocrine therapy (Tamoxifen & Aromatase Inhibitors)
Drug: Anastrozole Tablets
One 1 mg tablet taken orally once daily
Drug: Exemestane Tablets
One 25 mg tablet taken orally once daily
Drug: TOL2506
Leuprolide Acetate for injectable suspension, 30 mg. Subcutaneous injection every 3 months.
Drug: Tamoxifen
20 mg once daily or 10 mg 2 times daily - either tablet or solution
Drug: Letrozole Tablets
One 2.5 mg tablet taken orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Suppression of ovarian function
Time Frame: 6 weeks after the first administration of TOL2506
LH level < 4 IU/L at Week 6
6 weeks after the first administration of TOL2506

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Suppression of ovarian function overall (LH, E2, menses; treatments pooled)
Time Frame: Week 6 to Week 48
Percent of all subjects with LH < 4 IU/L, E2 <20 pg/mL in subjects treated with TOL2506 + endocrine therapy (tamoxifen or aromatase inhibitors) at every measurement from Week 6 to Week 48
Week 6 to Week 48
Suppression of ovarian function overall (LH, E2, menses; TOL2506 + tamoxifen)
Time Frame: Week 6 to Week 48
Percent of all subjects with LH < 4 IU/L, E2 <20 pg/mL in subjects treated with TOL2506 + tamoxifen at every measurement from Week 6 to Week 48
Week 6 to Week 48
Suppression of ovarian function overall (LH, E2; TOL2506 + aromatase inhibitor)
Time Frame: Week 6 to Week 48
Percent of all subjects with LH < 4 IU/L, E2 <20 pg/mL in subjects treated with TOL2506 + aromatase inhibitor at every measurement from Week 6 to Week 48
Week 6 to Week 48

Collaborators and Investigators

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

Sponsor

Tolmar Inc.

Investigators

  • Principal Investigator: E P Hamilton, SCRI Development Innovations, LLC

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)

July 1, 2021

Primary Completion (Estimated)

April 30, 2026

Study Completion (Estimated)

April 30, 2026

Study Registration Dates

First Submitted

May 12, 2021

First Submitted That Met QC Criteria

May 24, 2021

First Posted (Actual)

May 28, 2021

Study Record Updates

Last Update Posted (Estimated)

January 13, 2026

Last Update Submitted That Met QC Criteria

January 9, 2026

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TOL2506A

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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