Ovarian Suppression Evaluating Subcutaneous Leuprolide Acetate in Breast Cancer

NCT ID: NCT04906395

Last Updated: 2026-01-13

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-01
• Study Completion Date: 2026-04-30

Brief Summary

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Active Comparator: TOL2506

TOL2506 in combinatination with standard endocrine therapy (Tamoxifen \& Aromatase Inhibitors)

Group Type: EXPERIMENTAL

TOL2506

Intervention Type: DRUG

Leuprolide Acetate for injectable suspension, 30 mg. Subcutaneous injection every 3 months.

Tamoxifen

Intervention Type: DRUG

20 mg once daily or 10 mg 2 times daily - either tablet or solution

Letrozole Tablets

Intervention Type: DRUG

One 2.5 mg tablet taken orally once daily

Anastrozole Tablets

Intervention Type: DRUG

One 1 mg tablet taken orally once daily

Exemestane Tablets

Intervention Type: DRUG

One 25 mg tablet taken orally once daily

Interventions

TOL2506

Leuprolide Acetate for injectable suspension, 30 mg. Subcutaneous injection every 3 months.

Intervention Type: DRUG

Tamoxifen

20 mg once daily or 10 mg 2 times daily - either tablet or solution

Intervention Type: DRUG

Letrozole Tablets

One 2.5 mg tablet taken orally once daily

Intervention Type: DRUG

Anastrozole Tablets

One 1 mg tablet taken orally once daily

Intervention Type: DRUG

Exemestane Tablets

One 25 mg tablet taken orally once daily

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 49 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tolmar Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

E P Hamilton

Role: PRINCIPAL_INVESTIGATOR

SCRI Development Innovations, LLC

Locations

Marin Cancer Care, Inc

Greenbrae, California, United States

Cypress Hematology and Oncology

Parker, Colorado, United States

Mount Sinai Hospital

Chicago, Illinois, United States

Baptist Health Louisville

Louisville, Kentucky, United States

Maryland Oncology Hematology, P.A.

Glenn Dale, Maryland, United States

Nebraska Cancer Specialists

Omaha, Nebraska, United States

Montefiore - Einstein Center for Cancer Care at Montefiore Medical Park

The Bronx, New York, United States

Oncology Hematology Care Clinical Trials

Cincinnati, Ohio, United States

Lankenau Medical Center

Wynnewood, Pennsylvania, United States

Tennessee Oncology, PLLC

Chattanooga, Tennessee, United States

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Texas Oncology-Austin

Austin, Texas, United States

Texas Oncology- Dallas Presbyterian Hospital

Dallas, Texas, United States

Texas Oncology- San Antonio

New Braunfels, Texas, United States

Texas Oncology- Northeast Texas

Tyler, Texas, United States

Texas Oncology- Deke Slayton Cancer Center

Webster, Texas, United States

Seattle Cancer Center Alliance

Seattle, Washington, United States

Hospital Britanico de Buenos Aires

Buenos Aires, Buenos Aires F.D., Argentina

Instituto Oncologico de Cordoba (IONC)

Córdoba, Córdoba Province, Argentina

Centro Privado de RMI Rio Cuarto

Río Cuarto, Córdoba Province, Argentina

Instituto Medico de la Fundacion Estudios Clinicos

Rosario, Santa Fe Province, Argentina

Hospital Provincial del Centenario

Rosario, Santa Fe Province, Argentina

Hospital Aleman

Buenos Aires, , Argentina

Fundacion CENIT

CABA, , Argentina

Sanatorio Allende- Sede Nueva Cordoba

Córdoba, , Argentina

Oncocentro Servicos Medicos e Hospitalares Ltda

Fortaleza, Ceará, Brazil

Centro Regional Integrado de Oncologia

Fortaleza, Ceará, Brazil

Hospital Sao Rafael

Salvador, Estado de Bahia, Brazil

Hospital Araujo Jorge

Goiânia, Goiás, Brazil

Onconeo

Campo Grande, Mato Grosso do Sul, Brazil

Hospital do Cancer de Londrina

Londrina, Paraná, Brazil

Uniao Brasileira de Educacao e Assistencia

Porto Alegre, Rio Grande do Sul, Brazil

Hospital de Amor Amazonia

Porto Velho, Rondônia, Brazil

Fundacao Pio XII

Barretos, São Paulo, Brazil

Centro de Estudos e Pesquisas de Hematologia e Oncologia da Faculdade de Medicina do ABC

Santo André, São Paulo, Brazil

Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria

São Paulo, São Paulo, Brazil

Irmamandade de Santa Casa de Misericordia de Porto Alegre

Porto Alegre, , Brazil

Instituto de Educacao, Pesquisa e Gestao em Saude

Rio de Janeiro, , Brazil

Sunnybrook Odette Cancer Centre Clinical Research Program

Toronto, Ontario, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

HCG City Cancer Centre

Vijayawada, Andhra Pradesh, India

Apollo Hospitals

Visakhapatnam, Andhra Pradesh, India

HCG Cancer Centre

Visakhapatnam, Andhra Pradesh, India

Hemato Oncology Clinic Ahmedabad Pvt. Ltd.

Ahmedabad, Gujarat, India

Unique Hospital Multispecialty & Research Institute

Surat, Gujarat, India

SRV AGADI Hospital and Research Centre

Bengaluru, Karnataka, India

Oncoville Cancer Hospital and Research Center

Bengaluru, Karnataka, India

Mysore Medical College and Research Institute

Mysore, Karnataka, India

KIMS-Kingsway Hospitals, SPANV Medisearch Lifesciences

Nagpur, Maharashtra, India

HCG Manavata Cancer Centre

Nashik, Maharashtra, India

Indrayani Hospital and Cancer Institute

Pune, Maharashtra, India

Erode Cancer Centre Private Ltd.

Erode, Tamil Nadu, India

Apollo Cancer Hospitals

Hyderabad, Telangana, India

Swami Harshankaranand Ji Hospital & Research Centre

Varanasi, Uttar Pradesh, India

Amiisto Atencion Medica Integral, Investigacion Y Terapia Oncologica S.A De C.V.

Mexico City, Mexico City, Mexico

Unidad de Medicina Especializada SMA

San Juan del Río, Querétaro, Mexico

Clinica EMA

Mexico City, , Mexico

FAICIC S. de R.L. de C.V.

Veracruz, , Mexico

FDI Clinical Research

San Juan, , Puerto Rico

Countries

United States; Argentina; Brazil; Canada; India; Mexico; Puerto Rico

Other Identifiers

TOL2506A

Identifier Type: -

Identifier Source: org_study_id