Ovarian Suppression Evaluating Subcutaneous Leuprolide Acetate in Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT04906395
- Lead Sponsor
- Tolmar Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 250
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.
-
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:
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Active Comparator: TOL2506 TOL2506 TOL2506 in combinatination with standard endocrine therapy (Tamoxifen \& Aromatase Inhibitors) Active Comparator: TOL2506 Letrozole Tablets TOL2506 in combinatination with standard endocrine therapy (Tamoxifen \& Aromatase Inhibitors) Active Comparator: TOL2506 Anastrozole Tablets TOL2506 in combinatination with standard endocrine therapy (Tamoxifen \& Aromatase Inhibitors) Active Comparator: TOL2506 Exemestane Tablets TOL2506 in combinatination with standard endocrine therapy (Tamoxifen \& Aromatase Inhibitors) Active Comparator: TOL2506 Tamoxifen TOL2506 in combinatination with standard endocrine therapy (Tamoxifen \& Aromatase Inhibitors)
- Primary Outcome Measures
Name Time Method Suppression of ovarian function 6 weeks after the first administration of TOL2506 LH level \< 4 IU/L at Week 6
- Secondary Outcome Measures
Name Time Method Suppression of ovarian function overall (LH, E2; TOL2506 + aromatase inhibitor) Week 6 to Week 48 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
Suppression of ovarian function overall (LH, E2, menses; treatments pooled) Week 6 to Week 48 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
Suppression of ovarian function overall (LH, E2, menses; TOL2506 + tamoxifen) Week 6 to Week 48 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
Trial Locations
- Locations (117)
Texas Oncology- Deke Slayton Cancer Center
🇺🇸Webster, Texas, United States
Hospital Araujo Jorge
🇧🇷Goiania, Goias, Brazil
Marin Cancer Care, Inc
🇺🇸Greenbrae, California, United States
Cypress Hematology and Oncology
🇺🇸Parker, Colorado, United States
Cancer Care Centers of Brevard, Inc.
🇺🇸Melbourne, Florida, 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
🇺🇸Bronx, New York, United States
Oncology Hematology Care Clinical Trials
🇺🇸Cincinnati, Ohio, United States
Lankenau Medical Center
🇺🇸Wynnewood, Pennsylvania, 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
Seattle Cancer Center Alliance
🇺🇸Seattle, Washington, United States
Hospital Britanico de Buenos Aires
🇦🇷Buenos Aires, Caba, 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, Argentina
Hospital Provincial del Centenario
🇦🇷Rosario, Santa Fe, Argentina
Fundacion CENIT
🇦🇷Caba, Argentina
Hospital Aleman
🇦🇷Ciudad autónoma de Buenos Aires, Argentina
Sanatorio Allende- Sede Nueva Cordoba
🇦🇷Cordoba, Argentina
Hospital Sao Rafael
🇧🇷Salvador, Bahia, Brazil
Oncocentro Servicos Medicos e Hospitalares Ltda
🇧🇷Fortaleza, Ceara, Brazil
Centro Regional Integrado de Oncologia
🇧🇷Fortaleza, Ceara, Brazil
Onconeo
🇧🇷Campo Grande, Mato Grosso Do Sul, Brazil
Hospital do Cancer de Londrina
🇧🇷Londrina, Parana, Brazil
Uniao Brasileira de Educacao e Assistencia
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital de Amor Amazonia
🇧🇷Porto Velho, Rondonia, Brazil
Fundacao Pio XII
🇧🇷Barretos, Sao Paulo, 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, 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
🇮🇳Sūrat, 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, Cdmx, Mexico
Unidad de Medicina Especializada SMA
🇲🇽San Juan del Rio, Queretaro, Mexico
Clinica EMA
🇲🇽Mexico City, Mexico
FAICIC S. de R.L. de C.V.
🇲🇽Veracruz, Mexico
FDI Clinical Research
🇵🇷San Juan, Puerto Rico
Hospital Provincial del Centenario
🇦🇷Rosario, Santa Fe, Argentina
Fundacion CENIT
🇦🇷Caba, Argentina
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
🇺🇸Bronx, New York, United States
Oncology Hematology Care Clinical Trials
🇺🇸Cincinnati, Ohio, United States
Lankenau Medical Center
🇺🇸Wynnewood, Pennsylvania, 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, Caba, 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, Argentina
Hospital Aleman
🇦🇷Ciudad autónoma de Buenos Aires, Argentina
Sanatorio Allende- Sede Nueva Cordoba
🇦🇷Cordoba, Argentina
Hospital Sao Rafael
🇧🇷Salvador, Bahia, Brazil
Oncocentro Servicos Medicos e Hospitalares Ltda
🇧🇷Fortaleza, Ceara, Brazil
Centro Regional Integrado de Oncologia
🇧🇷Fortaleza, Ceara, Brazil
Hospital Araujo Jorge
🇧🇷Goiania, Goias, Brazil
Onconeo
🇧🇷Campo Grande, Mato Grosso Do Sul, Brazil
Hospital do Cancer de Londrina
🇧🇷Londrina, Parana, Brazil
Uniao Brasileira de Educacao e Assistencia
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital de Amor Amazonia
🇧🇷Porto Velho, Rondonia, Brazil
Fundacao Pio XII
🇧🇷Barretos, Sao Paulo, 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, 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
🇮🇳Sūrat, 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, Cdmx, Mexico
Unidad de Medicina Especializada SMA
🇲🇽San Juan del Rio, Queretaro, Mexico
Clinica EMA
🇲🇽Mexico City, Mexico
FAICIC S. de R.L. de C.V.
🇲🇽Veracruz, Mexico
FDI Clinical Research
🇵🇷San Juan, Puerto Rico