Status and phase
Conditions
Treatments
About
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.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
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:
Exclusion criteria
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:
Unacceptable renal function as determined by any of the following:
History of significantly abnormal ECG or screening 12-lead ECG demonstrating any of the following:
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:
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
Primary purpose
Allocation
Interventional model
Masking
250 participants in 1 patient group
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Central trial contact
Kerlin Lynch
Data sourced from clinicaltrials.gov
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