Clinical trial NCT04906395: Ovarian Suppression Evaluating Subcutaneous Leuprolide Acetate in Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Keywords: Ovarian Suppression
HR+
HER2-
Oncology
Premenopausal
Lead sponsor: Tolmar Inc.
Sponsor class: INDUSTRY
First posted: 2021-05-28
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Suppression of ovarian function
timeFrame: 6 weeks after the first administration of TOL2506
Secondary outcomes:
measure: Suppression of ovarian function overall (LH, E2, menses; treatments pooled)
timeFrame: Week 6 to Week 48
measure: Suppression of ovarian function overall (LH, E2, menses; TOL2506 + tamoxifen)
timeFrame: Week 6 to Week 48
measure: Suppression of ovarian function overall (LH, E2; TOL2506 + aromatase inhibitor)
timeFrame: Week 6 to Week 48
Other outcomes:
Locations:
city: Greenbrae
country: United States
facility: Marin Cancer Care, Inc
state: California
city: Parker
country: United States
facility: Cypress Hematology and Oncology
state: Colorado
city: Chicago
country: United States
facility: Mount Sinai Hospital
state: Illinois
city: Louisville
country: United States
facility: Baptist Health Louisville
state: Kentucky
city: Glenn Dale
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Bronx
country: United States
facility: Montefiore - Einstein Center for Cancer Care at Montefiore Medical Park
state: New York
city: Cincinnati
country: United States
facility: Oncology Hematology Care Clinical Trials
state: Ohio
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
city: Chattanooga
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology-Austin
state: Texas
city: Dallas
country: United States
facility: Texas Oncology- Dallas Presbyterian Hospital
state: Texas
city: New Braunfels
country: United States
facility: Texas Oncology- San Antonio
state: Texas
city: Tyler
country: United States
facility: Texas Oncology- Northeast Texas
state: Texas
city: Webster
country: United States
facility: Texas Oncology- Deke Slayton Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Center Alliance
state: Washington
city: Buenos Aires
country: Argentina
facility: Hospital Britanico de Buenos Aires
state: Caba
city: Córdoba
country: Argentina
facility: Instituto Oncologico de Cordoba (IONC)
state: Cordoba
city: Río Cuarto
country: Argentina
facility: Centro Privado de RMI Rio Cuarto
state: Cordoba
city: Rosario
country: Argentina
facility: Instituto Medico de la Fundacion Estudios Clinicos
state: Santa Fe
city: Rosario
country: Argentina
facility: Hospital Provincial del Centenario
state: Santa Fe
city: Caba
country: Argentina
facility: Fundacion CENIT
city: Ciudad autónoma de Buenos Aires
country: Argentina
facility: Hospital Aleman
city: Cordoba
country: Argentina
facility: Sanatorio Allende- Sede Nueva Cordoba
city: Salvador
country: Brazil
facility: Hospital Sao Rafael
state: Bahia
city: Fortaleza
country: Brazil
facility: Oncocentro Servicos Medicos e Hospitalares Ltda
state: Ceara
city: Fortaleza
country: Brazil
facility: Centro Regional Integrado de Oncologia
state: Ceara
city: Goiania
country: Brazil
facility: Hospital Araujo Jorge
state: Goias
city: Campo Grande
country: Brazil
facility: Onconeo
state: Mato Grosso Do Sul
city: Londrina
country: Brazil
facility: Hospital do Cancer de Londrina
state: Parana
city: Porto Alegre
country: Brazil
facility: Uniao Brasileira de Educacao e Assistencia
state: Rio Grande Do Sul
city: Porto Velho
country: Brazil
facility: Hospital de Amor Amazonia
state: Rondonia
city: Barretos
country: Brazil
facility: Fundacao Pio XII
state: Sao Paulo
city: Santo André
country: Brazil
facility: Centro de Estudos e Pesquisas de Hematologia e Oncologia da Faculdade de Medicina do ABC
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria
state: Sao Paulo
city: Porto Alegre
country: Brazil
facility: Irmamandade de Santa Casa de Misericordia de Porto Alegre
city: Rio De Janeiro
country: Brazil
facility: Instituto de Educacao, Pesquisa e Gestao em Saude
city: Toronto
country: Canada
facility: Sunnybrook Odette Cancer Centre Clinical Research Program
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Vijayawada
country: India
facility: HCG City Cancer Centre
state: Andhra Pradesh
city: Visakhapatnam
country: India
facility: Apollo Hospitals
state: Andhra Pradesh
city: Visakhapatnam
country: India
facility: HCG Cancer Centre
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: Hemato Oncology Clinic Ahmedabad Pvt. Ltd.
state: Gujarat
city: Sūrat
country: India
facility: Unique Hospital Multispecialty & Research Institute
state: Gujarat
city: Bengaluru
country: India
facility: SRV AGADI Hospital and Research Centre
state: Karnataka
city: Bengaluru
country: India
facility: Oncoville Cancer Hospital and Research Center
state: Karnataka
city: Mysore
country: India
facility: Mysore Medical College and Research Institute
state: Karnataka
city: Nagpur
country: India
facility: KIMS-Kingsway Hospitals, SPANV Medisearch Lifesciences
state: Maharashtra
city: Nashik
country: India
facility: HCG Manavata Cancer Centre
state: Maharashtra
city: Pune
country: India
facility: Indrayani Hospital and Cancer Institute
state: Maharashtra
city: Erode
country: India
facility: Erode Cancer Centre Private Ltd.
state: Tamil Nadu
city: Hyderabad
country: India
facility: Apollo Cancer Hospitals
state: Telangana
city: Varanasi
country: India
facility: Swami Harshankaranand Ji Hospital & Research Centre
state: Uttar Pradesh
city: Mexico City
country: Mexico
facility: Amiisto Atencion Medica Integral, Investigacion Y Terapia Oncologica S.A De C.V.
state: Cdmx
city: San Juan del Rio
country: Mexico
facility: Unidad de Medicina Especializada SMA
state: Queretaro
city: Mexico City
country: Mexico
facility: Clinica EMA
city: Veracruz
country: Mexico
facility: FAICIC S. de R.L. de C.V.
city: San Juan
country: Puerto Rico
facility: FDI Clinical Research
Study officials:
affiliation: SCRI Development Innovations, LLC
name: E P Hamilton
role: PRINCIPAL_INVESTIGATOR
References: