Ovarian Suppression Evaluating Subcutaneous Leuprolide Acetate in Breast Cancer

Breast Cancer Clinical Trial

— OVELIA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04906395
• Other study ID #: TOL2506A
• Status: Recruiting
• Phase: Phase 3
• Start date: July 1, 2021
• Est. completion date: April 30, 2025

Study information

• Verified date: July 2023
• Source: Tolmar Inc.
• Contact: A Mehta
• Phone: 919-589-2121
• Email: amehta[@]caidya.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: April 30, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 49 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• TOL2506
Leuprolide Acetate for injectable suspension, 30 mg. Subcutaneous injection every 3 months.
• Tamoxifen
20 mg once daily or 10 mg 2 times daily - either tablet or solution
• Letrozole Tablets
One 2.5 mg tablet taken orally once daily
• Anastrozole Tablets
One 1 mg tablet taken orally once daily
• Exemestane Tablets
One 25 mg tablet taken orally once daily

Locations

Country	Name	City	State
Argentina	Hospital Britanico de Buenos Aires	Buenos Aires	Caba
Argentina	Fundacion CENIT	Caba
Argentina	Hospital Aleman	Ciudad autónoma de Buenos Aires
Argentina	Sanatorio Allende- Sede Nueva Cordoba	Cordoba
Argentina	Instituto Oncologico de Cordoba (IONC)	Córdoba	Cordoba
Argentina	Centro Privado de RMI Rio Cuarto	Río Cuarto	Cordoba
Argentina	Instituto Medico de la Fundacion Estudios Clinicos	Rosario	Santa Fe
Brazil	Fundacao Pio XII	Barretos	Sao Paulo
Brazil	Onconeo	Campo Grande	Mato Grosso Do Sul
Brazil	Hospital Erasto Gaertner	Curitiba	Parana
Brazil	Centro Regional Integrado de Oncologia	Fortaleza	Ceara
Brazil	Oncocentro Servicos Medicos e Hospitalares Ltda	Fortaleza	Ceara
Brazil	Hospital Araujo Jorge	Goiania	Goias
Brazil	Hospital do Cancer de Londrina	Londrina	Parana
Brazil	Irmamandade de Santa Casa de Misericordia de Porto Alegre	Porto Alegre
Brazil	Uniao Brasileira de Educacao e Assistencia	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital de Amor Amazonia	Porto Velho	Rondonia
Brazil	Instituto D Or de Pesquisa e Ensino - Hospital Esperanca Recife	Recife	Pernambuco
Brazil	Instituto de Educacao, Pesquisa e Gestao em Saude	Rio De Janeiro
Brazil	Hospital Sao Rafael	Salvador	Bahia
Brazil	Centro de Estudos e Pesquisas de Hematologia e Oncologia da Faculdade de Medicina do ABC	Santo André	Sao Paulo
Brazil	Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria	São Paulo	Sao Paulo
Canada	Lions Gate Hospital	North Vancouver	British Columbia
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Sunnybrook Odette Cancer Centre Clinical Research Program	Toronto	Ontario
Mexico	Amiisto Atencion Medica Integral, Investigacion Y Terapia Oncologica S.A De C.V.	Mexico City	Cdmx
Mexico	Clinica EMA	Mexico City
Mexico	Unidad de Medicina Especializada SMA	San Juan del Rio	Queretaro
Mexico	FAICIC S. de R.L. de C.V.	Veracruz
Puerto Rico	FDI Clinical Research	San Juan
United States	Texas Oncology-Austin	Austin	Texas
United States	St. Vincent - Frontier Cancer Center	Billings	Montana
United States	Montefiore - Einstein Center for Cancer Care at Montefiore Medical Park	Bronx	New York
United States	Tennessee Oncology, PLLC	Chattanooga	Tennessee
United States	Mount Sinai Hospital	Chicago	Illinois
United States	Oncology Hematology Care Clinical Trials	Cincinnati	Ohio
United States	Texas Oncology- Dallas Presbyterian Hospital	Dallas	Texas
United States	Hematology Oncology Associates of Central New York, PC	East Syracuse	New York
United States	Carolina Institute for Clinical Research	Fayetteville	North Carolina
United States	Holy Cross Hospital - Bienes Cancer Center	Fort Lauderdale	Florida
United States	Maryland Oncology Hematology, P.A.	Glenn Dale	Maryland
United States	Marin Cancer Care, Inc	Greenbrae	California
United States	Baptist Health Lexington	Lexington	Kentucky
United States	Baptist Health Louisville	Louisville	Kentucky
United States	Joe Arrington Cancer Research & Treatment Center	Lubbock	Texas
United States	Cancer Care Centers of Brevard, Inc.	Melbourne	Florida
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Texas Oncology- San Antonio	New Braunfels	Texas
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	Cypress Hematology and Oncology	Parker	Colorado
United States	Seattle Cancer Center Alliance	Seattle	Washington
United States	Texas Oncology- Northeast Texas	Tyler	Texas
United States	Texas Oncology- Deke Slayton Cancer Center	Webster	Texas
United States	Lankenau Medical Center	Wynnewood	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Tolmar Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Mexico,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Suppression of ovarian function	LH level < 4 IU/L at Week 6	6 weeks after the first administration of TOL2506
Secondary	Suppression of ovarian function overall (LH, E2, menses; treatments pooled)	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
Secondary	Suppression of ovarian function overall (LH, E2, menses; TOL2506 + tamoxifen)	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
Secondary	Suppression of ovarian function overall (LH, E2; TOL2506 + aromatase inhibitor)	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