Breast CancerPhase 3OVELIANCT04906395
Ovarian Suppression Evaluating Subcutaneous Leuprolide Acetate in Breast Cancer
A Phase 3 study testing TOL2506, Tamoxifen and Letrozole Tablets in people with Breast Cancer, run by Tolmar Inc. at 59 sites in 7 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 49 years
- Conditions the study is for
- Breast Cancer
- What is being tested?
- TOL2506, Tamoxifen and Letrozole Tablets
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 59 sitesin 7 countries
- Study dates
- 1 Jul 2021to 30 Jan 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 49 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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)
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- 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:
- HR > 100 BPM
- QRS > 120 msec
- QTc > 450 msec
- PR > 220 msec
- Prior (within 28 days prior to Day 1) and/or concomitant use of medications known to prolong the QT/QTc interval
- 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
- Concomitant use of anticancer mediations other than those specified for use by the protocol
- Prior neoadjuvant or adjuvant endocrine therapy since diagnosis of breast cancer
- History of treatment for osteopenia/osteoporosis or baseline bone mineral density Z-score ≤ -2.0
- 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
- 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)
- 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)
- 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
- Already receiving and/or previously received GnRH analogs within 1 year before breast cancer diagnosis
- Psychiatric, addictive, or other disorders that would preclude study compliance
- Use of medications that may impact subject safety and/or affect the PK of the drug and hormonal assessments including but not limited to:
- Oral or transdermal hormonal therapy within 30 days prior to subject's first visit
- Estrogen, progesterone, or androgens within 30 days prior to subject's first visit
- Hormonal contraceptives within 30 days prior to subject's first visit
- Medications known to result in clinically important decreases in bone mass taken within 6 months prior to subject's first visit
- Known hypersensitivity, idiosyncratic, or allergic reactions to GnRH, GnRH agonist/analogs or to any of the components of the IP
- Sexually active with a male partner and not willing to use non-hormonal contraceptive methods throughout the study
- Is of childbearing potential with a positive serum pregnancy test at Screening or urine pregnancy test at Day 1
- 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
Trial locations and contacts
59 sites in 7 countries.
59 sites in 7 countries
United States17 sites
Texas Oncology-Austin
Austin, Texas, 78731
Tennessee Oncology, PLLC
Chattanooga, Tennessee, 37404
Mount Sinai Hospital
Chicago, Illinois, 60608
Oncology Hematology Care Clinical Trials
Cincinnati, Ohio, 45211
Texas Oncology- Dallas Presbyterian Hospital
Dallas, Texas, 75231
Maryland Oncology Hematology, P.A.
Glenn Dale, Maryland, 20769
Marin Cancer Care, Inc
Greenbrae, California, 94904
Baptist Health Louisville
Louisville, Kentucky, 40207
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
Texas Oncology- San Antonio
New Braunfels, Texas, 78130
Nebraska Cancer Specialists
Omaha, Nebraska, 68114
Cypress Hematology and Oncology
Parker, Colorado, 80138
Seattle Cancer Center Alliance
Seattle, Washington, 98109
Montefiore - Einstein Center for Cancer Care at Montefiore Medical Park
The Bronx, New York, 10461
Texas Oncology- Northeast Texas
Tyler, Texas, 75702
Texas Oncology- Deke Slayton Cancer Center
Webster, Texas, 77598
Lankenau Medical Center
Wynnewood, Pennsylvania, 19096
India14 sites
Hemato Oncology Clinic Ahmedabad Pvt. Ltd.
Ahmedabad, Gujarat, 380054
SRV AGADI Hospital and Research Centre
Bengaluru, Karnataka, 560027
Oncoville Cancer Hospital and Research Center
Bengaluru, Karnataka, 560072
Erode Cancer Centre Private Ltd.
Erode, Tamil Nadu, 638012
Apollo Cancer Hospitals
Hyderabad, Telangana, 500096
Mysore Medical College and Research Institute
Mysore, Karnataka, 570001
KIMS-Kingsway Hospitals, SPANV Medisearch Lifesciences
Nagpur, Maharashtra, 440001
HCG Manavata Cancer Centre
Nashik, Maharashtra, 42202
Indrayani Hospital and Cancer Institute
Pune, Maharashtra, 412105
Unique Hospital Multispecialty & Research Institute
Surat, Gujarat, 395002
Swami Harshankaranand Ji Hospital & Research Centre
Varanasi, Uttar Pradesh, 221004
HCG City Cancer Centre
Vijayawada, Andhra Pradesh, 520002
Apollo Hospitals
Visakhapatnam, Andhra Pradesh, 530040
HCG Cancer Centre
Visakhapatnam, Andhra Pradesh, 530040
Brazil13 sites
Fundacao Pio XII
Barretos, São Paulo, 14784-400
Onconeo
Campo Grande, Mato Grosso do Sul, 79002-061
Oncocentro Servicos Medicos e Hospitalares Ltda
Fortaleza, Ceará, 60135-237
Centro Regional Integrado de Oncologia
Fortaleza, Ceará, 60335-480
Hospital Araujo Jorge
Goiânia, Goiás, 74605-070
Hospital do Cancer de Londrina
Londrina, Paraná, 86015-520
Uniao Brasileira de Educacao e Assistencia
Porto Alegre, Rio Grande do Sul, 90610-000
Irmamandade de Santa Casa de Misericordia de Porto Alegre
Porto Alegre, 90020-090
Hospital de Amor Amazonia
Porto Velho, Rondônia, 76834-899
Instituto de Educacao, Pesquisa e Gestao em Saude
Rio de Janeiro, 22775-001
Hospital Sao Rafael
Salvador, Estado de Bahia, 41253-190
Centro de Estudos e Pesquisas de Hematologia e Oncologia da Faculdade de Medicina do ABC
Santo André, São Paulo, 09060-650
Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria
São Paulo, São Paulo, 01317-001
Argentina8 sites
Hospital Britanico de Buenos Aires
Buenos Aires, Buenos Aires F.D., C1480AEB
Hospital Aleman
Buenos Aires, C118AAT
Fundacion CENIT
CABA, C1125ABD
Instituto Oncologico de Cordoba (IONC)
Córdoba, Córdoba Province, 5000
Sanatorio Allende- Sede Nueva Cordoba
Córdoba, X5000JHQ
Centro Privado de RMI Rio Cuarto
Río Cuarto, Córdoba Province, 5800
Instituto Medico de la Fundacion Estudios Clinicos
Rosario, Santa Fe Province, S2000DEJ
Hospital Provincial del Centenario
Rosario, Santa Fe Province, S2000KDS
Mexico4 sites
Amiisto Atencion Medica Integral, Investigacion Y Terapia Oncologica S.A De C.V.
Mexico City, Mexico City, 07300
Clinica EMA
Mexico City, 03339
Unidad de Medicina Especializada SMA
San Juan del Río, Querétaro, 76800
FAICIC S. de R.L. de C.V.
Veracruz, 91900
Canada2 sites
Sunnybrook Odette Cancer Centre Clinical Research Program
Toronto, Ontario, M4N 3M5
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 1Z5
About this study
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
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
- Being tested
- TOL2506, Tamoxifen, Letrozole Tablets, Anastrozole Tablets, Exemestane Tablets
- Keywords
- Ovarian Suppression, HR+, HER2-, Oncology, Premenopausal
- Medical subject headings
- Breast Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TOL2506Drug
Leuprolide Acetate for injectable suspension, 30 mg. Subcutaneous injection every 3 months.
TamoxifenDrug
20 mg once daily or 10 mg 2 times daily - either tablet or solution
Letrozole TabletsDrug
One 2.5 mg tablet taken orally once daily
Anastrozole TabletsDrug
One 1 mg tablet taken orally once daily
Exemestane TabletsDrug
One 25 mg tablet taken orally once daily
| Study group | Role | What they receive |
|---|---|---|
| Active Comparator: TOL2506 | Experimental | TOL2506 in combinatination with standard endocrine therapy (Tamoxifen \& Aromatase Inhibitors) Receives: Drug: TOL2506; Drug: Tamoxifen; Drug: Letrozole Tablets; Drug: Anastrozole Tablets; Drug: Exemestane Tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Suppression of ovarian function
LH level < 4 IU/L at Week 6
Measured: 6 weeks after the first administration of TOL2506
Secondary outcomes (3)
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
Measured: 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
Measured: 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
Measured: Week 6 to Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2021
- Study start1 Jul 2021
- Primary completion30 Jan 2027 (estimated)
- Study completion30 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tolmar Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- E P Hamilton, Principal investigator, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04906395
- Sponsor's protocol ID
- TOL2506A
- Acronym
- OVELIA
- Status last verified
- Oct 2026
- First submitted
- 12 May 2021
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No