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

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: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Anastrozole Tablets; Drug: Exemestane Tablets; Drug: TOL2506; Drug: Tamoxifen; Drug: Letrozole Tablets

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: A Mehta; Phone Number: 2121 919-589-2121; Email: amehta@caidya.com
• Study Contact Backup: Name: C Fajardo; Phone Number: 702-569-6355; Email: cris.fajardo@caidya.com

Study Locations

• Argentina
  • Ciudad autónoma de Buenos Aires, Argentina, C118AAT
    • Recruiting
    • Hospital Aleman
  • Cordoba, Argentina, X5000JHQ
    • Recruiting
    • Sanatorio Allende- Sede Nueva Cordoba
  • Caba
    • Buenos Aires, Caba, Argentina, C1480AEB
      • Recruiting
      • Hospital Britanico de Buenos Aires
  • Cordoba
    • Córdoba, Cordoba, Argentina, 5000
      • Recruiting
      • Instituto Oncologico de Cordoba (IONC)
    • Río Cuarto, Cordoba, Argentina, 5800
      • Recruiting
      • Centro Privado de RMI Rio Cuarto
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000DEJ
      • Recruiting
      • Instituto Médico de la Fundación Estudios Clinicos
• Brazil
  • Porto Alegre, Brazil, 90020-090
    • Recruiting
    • Irmamandade de Santa Casa de Misericordia de Porto Alegre
  • Rio De Janeiro, Brazil, 22775-001
    • Recruiting
    • Instituto de Educação, Pesquisa e Gestão em Saúde
  • Bahia
    • Salvador, Bahia, Brazil, 41253-190
      • Recruiting
      • Hospital Sao Rafael
  • Ceara
    • Fortaleza, Ceara, Brazil, 60335-480
      • Recruiting
      • Centro Regional Integrado de Oncologia
    • Fortaleza, Ceara, Brazil, 60135-237
      • Recruiting
      • Oncocentro Serviços Medicos E Hospitalares Ltda
  • Goias
    • Goiania, Goias, Brazil, 74605-070
      • Recruiting
      • Hospital Araújo Jorge
  • Mato Grosso Do Sul
    • Campo Grande, Mato Grosso Do Sul, Brazil, 79002-061
      • Recruiting
      • Onconeo
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50070-480
      • Recruiting
      • Instituto D Or de Pesquisa e Ensino - Hospital Esperanca Recife
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
      • Recruiting
      • Uniao Brasileira de Educacao e Assistencia
  • Rondonia
    • Porto Velho, Rondonia, Brazil, 76834-899
      • Recruiting
      • Hospital de Amor Amazônia
  • Sao Paulo
    • Barretos, Sao Paulo, Brazil, 14784-400
      • Recruiting
      • Fundação PIO XII
    • Santo André, Sao Paulo, Brazil, 09060-650
      • Recruiting
      • Centro de Estudos e Pesquisas de Hematologia e Oncologia da Faculdade de Medicina do ABC
    • São Paulo, Sao Paulo, Brazil, 01317-001
      • Recruiting
      • Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria
• Canada
  • British Columbia
    • North Vancouver, British Columbia, Canada, V7L 2L7
      • Recruiting
      • Lions Gate Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5G 1Z5
      • Recruiting
      • Princess Margaret Cancer Centre
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Sunnybrook Odette Cancer Centre Clinical Research Program
• Mexico
  • Mexico City, Mexico, 03339
    • Recruiting
    • Clinica EMA
  • Veracruz, Mexico, 91900
    • Recruiting
    • FAICIC S. de R.L. de C.V.
  • Cdmx
    • Mexico City, Cdmx, Mexico, 07300
      • Recruiting
      • Amiisto Atencion Medica Integral, Investigacion Y Terapia Oncologica S.A De C.V.
  • Queretaro
    • San Juan del Rio, Queretaro, Mexico, 76800
      • Recruiting
      • Unidad de Medicina Especializada SMA
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Recruiting
    • FDI Clinical Research
• United States
  • Arizona
    • Glendale, Arizona, United States, 85308
      • Recruiting
      • Arizona Oncology Associates, PC
  • California
    • Greenbrae, California, United States, 94904
      • Recruiting
      • Marin Cancer Care, Inc
  • Colorado
    • Parker, Colorado, United States, 80138
      • Recruiting
      • Cypress Hematology and Oncology
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Recruiting
      • Holy Cross Hospital - Bienes Cancer Center
    • Melbourne, Florida, United States, 32935
      • Recruiting
      • Cancer Care Centers of Brevard, Inc.
  • Illinois
    • Chicago, Illinois, United States, 60608
      • Recruiting
      • Mount Sinai Hospital
    • Warrenville, Illinois, United States, 60555
      • Recruiting
      • Northwestern Medicine Cancer Center
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Recruiting
      • Baptist Health Lexington
    • Louisville, Kentucky, United States, 40207
      • Recruiting
      • Baptist Health Louisville
  • Maryland
    • Glenn Dale, Maryland, United States, 20769
      • Recruiting
      • Maryland Oncology Hematology, P.A.
  • Montana
    • Billings, Montana, United States, 59102
      • Recruiting
      • St. Vincent - Frontier Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Recruiting
      • Nebraska Cancer Specialists
  • New York
    • Bronx, New York, United States, 10461
      • Recruiting
      • Montefiore - Einstein Center for Cancer Care at Montefiore Medical Park
    • East Syracuse, New York, United States, 13057
      • Recruiting
      • Hematology Oncology Associates of Central New York, PC
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Fayetteville, North Carolina, United States, 28303
      • Recruiting
      • Carolina Institute for Clinical Research
  • Ohio
    • Cincinnati, Ohio, United States, 45211
      • Recruiting
      • Oncology Hematology Care Clinical Trials
  • Pennsylvania
    • Wynnewood, Pennsylvania, United States, 19096
      • Recruiting
      • Lankenau Medical Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Recruiting
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology, PLLC
  • Texas
    • Austin, Texas, United States, 78731
      • Recruiting
      • Texas Oncology-Austin
    • Dallas, Texas, United States, 75231
      • Recruiting
      • Texas Oncology- Dallas Presbyterian Hospital
    • Lubbock, Texas, United States, 79410
      • Recruiting
      • Joe Arrington Cancer Research & Treatment Center
    • New Braunfels, Texas, United States, 78130
      • Recruiting
      • Texas Oncology- San Antonio
    • Tyler, Texas, United States, 75702
      • Recruiting
      • Texas Oncology- Northeast Texas
    • Webster, Texas, United States, 77598
      • Recruiting
      • Texas Oncology- Deke Slayton Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Seattle Cancer Center Alliance

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

1

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	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)	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)	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)	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

• Sponsor: Tolmar Inc.
• Investigators: Principal Investigator: E P Hamilton, SCRI Development Innovations, LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): April 30, 2025

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 (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Oncology; HR+; HER2-; Premenopausal; Ovarian Suppression
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Letrozole; Tamoxifen; Anastrozole; Exemestane
• 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