Ovarian Suppression Evaluating Subcutaneous Leuprolide Acetate in Breast Cancer

NCT04906395 | Active Not Recruiting Phase 3 FDA Drug

• 1 other identifier: TOL2506A
• Study Type: interventional
• Target: 250
• Locations: 7 countries
• Sites: 59

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

Keywords

Ovarian Suppression; HR+; HER2-; Oncology; Premenopausal

Outcome Measures

Primary Outcomes (1)

• Suppression of ovarian function

  LH level \< 4 IU/L at Week 6

  6 weeks after the first administration of TOL2506

Secondary Outcomes (3)

• Suppression of ovarian function overall (LH, E2, menses; treatments pooled)

  Week 6 to Week 48

• Suppression of ovarian function overall (LH, E2, menses; TOL2506 + tamoxifen)

  Week 6 to Week 48

• Suppression of ovarian function overall (LH, E2; TOL2506 + aromatase inhibitor)

  Week 6 to Week 48

Study Arms (1)

Active Comparator: TOL2506

EXPERIMENTAL

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

Drug: TOL2506; Drug: Tamoxifen; Drug: Letrozole Tablets; Drug: Anastrozole Tablets; Drug: Exemestane Tablets

Interventions

TOL2506 DRUG

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

Active Comparator: TOL2506

Tamoxifen DRUG

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

Active Comparator: TOL2506

Letrozole Tablets DRUG

One 2.5 mg tablet taken orally once daily

Active Comparator: TOL2506

Anastrozole Tablets DRUG

One 1 mg tablet taken orally once daily

Active Comparator: TOL2506

Exemestane Tablets DRUG

One 25 mg tablet taken orally once daily

Active Comparator: TOL2506

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• Body mass index (BMI) \< 18.00 kg/m2 or \> 35.00 kg/m2
• Breastfeeding
• Life expectancy \< 12 months
• Eastern Cooperative Oncology Group (ECOG) performance status ≥ 3
• Unacceptable hepatic function as determined by any of the following:
• Alanine aminotransferase (ALT) ≥ 2X upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≥ 2X ULN
• Bilirubin ≥ 2X ULN
• Alkaline phosphatase ≥ 2X ULN
• Severe hepatic impairment (Child-Pugh Class C)
• Unacceptable renal function as determined by any of the following:
• Creatinine ≥ 3X ULN
• Creatinine clearance ≤ 30 mL/minute
• Creatinine clearance ≤ 60 mL/minute in subjects with bone density 1.5 standard deviations below the young adult normal mean
• History of significantly abnormal ECG or screening 12-lead ECG demonstrating any of the following:

Sponsors & Collaborators

• Tolmar Inc.: lead

Study Sites (59)

Marin Cancer Care, Inc

Greenbrae, California, 94904, United States

Location

Cypress Hematology and Oncology

Parker, Colorado, 80138, United States

Location

Mount Sinai Hospital

Chicago, Illinois, 60608, United States

Location

Baptist Health Louisville

Louisville, Kentucky, 40207, United States

Location

Maryland Oncology Hematology, P.A.

Glenn Dale, Maryland, 20769, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68114, United States

Location

Montefiore - Einstein Center for Cancer Care at Montefiore Medical Park

The Bronx, New York, 10461, United States

Location

Oncology Hematology Care Clinical Trials

Cincinnati, Ohio, 45211, United States

Location

Lankenau Medical Center

Wynnewood, Pennsylvania, 19096, United States

Location

Tennessee Oncology, PLLC

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

Texas Oncology-Austin

Austin, Texas, 78731, United States

Location

Texas Oncology- Dallas Presbyterian Hospital

Dallas, Texas, 75231, United States

Location

Texas Oncology- San Antonio

New Braunfels, Texas, 78130, United States

Location

Texas Oncology- Northeast Texas

Tyler, Texas, 75702, United States

Location

Texas Oncology- Deke Slayton Cancer Center

Webster, Texas, 77598, United States

Location

Seattle Cancer Center Alliance

Seattle, Washington, 98109, United States

Location

Hospital Britanico de Buenos Aires

Buenos Aires, Buenos Aires F.D., C1480AEB, Argentina

Location

Instituto Oncologico de Cordoba (IONC)

Córdoba, Córdoba Province, 5000, Argentina

Location

Centro Privado de RMI Rio Cuarto

Río Cuarto, Córdoba Province, 5800, Argentina

Location

Instituto Medico de la Fundacion Estudios Clinicos

Rosario, Santa Fe Province, S2000DEJ, Argentina

Location

Hospital Provincial del Centenario

Rosario, Santa Fe Province, S2000KDS, Argentina

Location

Hospital Aleman

Buenos Aires, C118AAT, Argentina

Location

Fundacion CENIT

CABA, C1125ABD, Argentina

Location

Sanatorio Allende- Sede Nueva Cordoba

Córdoba, X5000JHQ, Argentina

Location

Oncocentro Servicos Medicos e Hospitalares Ltda

Fortaleza, Ceará, 60135-237, Brazil

Location

Centro Regional Integrado de Oncologia

Fortaleza, Ceará, 60335-480, Brazil

Location

Hospital Sao Rafael

Salvador, Estado de Bahia, 41253-190, Brazil

Location

Hospital Araujo Jorge

Goiânia, Goiás, 74605-070, Brazil

Location

Onconeo

Campo Grande, Mato Grosso do Sul, 79002-061, Brazil

Location

Hospital do Cancer de Londrina

Londrina, Paraná, 86015-520, Brazil

Location

Uniao Brasileira de Educacao e Assistencia

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Hospital de Amor Amazonia

Porto Velho, Rondônia, 76834-899, Brazil

Location

Fundacao Pio XII

Barretos, São Paulo, 14784-400, Brazil

Location

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

Santo André, São Paulo, 09060-650, Brazil

Location

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

São Paulo, São Paulo, 01317-001, Brazil

Location

Irmamandade de Santa Casa de Misericordia de Porto Alegre

Porto Alegre, 90020-090, Brazil

Location

Instituto de Educacao, Pesquisa e Gestao em Saude

Rio de Janeiro, 22775-001, Brazil

Location

Sunnybrook Odette Cancer Centre Clinical Research Program

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1Z5, Canada

Location

HCG City Cancer Centre

Vijayawada, Andhra Pradesh, 520002, India

Location

Apollo Hospitals

Visakhapatnam, Andhra Pradesh, 530040, India

Location

HCG Cancer Centre

Visakhapatnam, Andhra Pradesh, 530040, India

Location

Hemato Oncology Clinic Ahmedabad Pvt. Ltd.

Ahmedabad, Gujarat, 380054, India

Location

Unique Hospital Multispecialty & Research Institute

Surat, Gujarat, 395002, India

Location

SRV AGADI Hospital and Research Centre

Bengaluru, Karnataka, 560027, India

Location

Oncoville Cancer Hospital and Research Center

Bengaluru, Karnataka, 560072, India

Location

Mysore Medical College and Research Institute

Mysore, Karnataka, 570001, India

Location

KIMS-Kingsway Hospitals, SPANV Medisearch Lifesciences

Nagpur, Maharashtra, 440001, India

Location

HCG Manavata Cancer Centre

Nashik, Maharashtra, 42202, India

Location

Indrayani Hospital and Cancer Institute

Pune, Maharashtra, 412105, India

Location

Erode Cancer Centre Private Ltd.

Erode, Tamil Nadu, 638012, India

Location

Apollo Cancer Hospitals

Hyderabad, Telangana, 500096, India

Location

Swami Harshankaranand Ji Hospital & Research Centre

Varanasi, Uttar Pradesh, 221004, India

Location

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

Mexico City, Mexico City, 07300, Mexico

Location

Unidad de Medicina Especializada SMA

San Juan del Río, Querétaro, 76800, Mexico

Location

Clinica EMA

Mexico City, 03339, Mexico

Location

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

Veracruz, 91900, Mexico

Location

FDI Clinical Research

San Juan, 00927, Puerto Rico

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasms

Interventions

Tamoxifen; Letrozole; Anastrozole; exemestane

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• E P Hamilton

  SCRI Development Innovations, LLC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2021
• First Posted: May 28, 2021
• Study Start: July 1, 2021
• Primary Completion: April 30, 2026
• Study Completion: April 30, 2026
• Last Updated: January 13, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

IN (14); ME (4); PR (1); US (17); CA (2); BR (13); AR (8)