Open-label, Safety Extension Study for Subjects with Hormone-Receptor- Positive (HR+), Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer Who Have Completed the Ovarian Suppression Evaluating Subcutaneous Leuprolide Acetate in Breast Cancer (OVELIA) Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Tolmar, Inc.
- 入组人数
- 220
- 试验地点
- 15
- 主要终点
- To assess the safety and tolerability of TOL2506 in premenopausal subjects with HR+, HER2-negative breast cancer.
研究概览
简要总结
This is an open-label, safety extension study that will assess the safety and tolerability of TOL2506 (leuprolide acetate for injectable suspension, 30 mg) in combination with tamoxifen or an AI in subjects who participated in the TOL2506A study. Eligible subjects are those who received 4 injections of TOL2506, completed the 48-week treatment period and are candidates to continue receiving TOL2506 as GnRH therapy for the purpose of ovarian suppression. Male subjects who completed the Week 48 visit of the TOL2506A study can also be considered for eligibility to enroll in the TOL2506A-EXT study.
At Visit 8 (Week 36) of the TOL2506A study, Investigators will inform subjects of the potential to enroll in TOL2506A-EXT after they complete their next scheduled visit (Visit 9; Week 48). At Visit 9, Week 48 of TOL2506A, subjects will complete the final End-of-Study assessments and eligible subjects will be offered the option to participate in the TOL2506A-EXT study and continue receiving their previous TOL2506 + endocrine therapy for up to 4 years. Eligible subjects will enroll directly from the TOL2506A study into the TOL2506A-EXT study after having met all eligibility criteria. The assessments performed at Visit 9, Week 48 of TOL2506A will be used as the Screening assessments for TOL2506A-EXT (ie, assessments do not need to be repeated for Screening).
The total duration of the TOL2506A-EXT study is 205 weeks (~4 years). Enrolled subjects will receive TOL2506 every 12 weeks (84 ± 3 days) concurrently with their previous treatment of tamoxifen or an AI. Subjects will be allowed to switch from receiving an AI to receiving tamoxifen or from tamoxifen to AI at the discretion of the Investigator. Eligible subjects may continue to receive TOL2506 for up to 4 years
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 49.00 Year(s)（—）
- 性别
- All
入选标准
- •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 greater than 1 percent and/or, PR greater than 1 percent, HER2-negative per ASCO CAP guidelines).
- •Is a candidate for endocrine therapy + ovarian suppression LH greater than 4 IU per L within 28 days prior to Day
- •Is premenopausal as defined by E2 greater than 30 pg per mL follicle-stimulating hormone (FSH) less than 40 IU per L regular menses (eg, menstrual cycle length of 21 to 35 days) Note: premenopausal status must be determined before neo or 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.
排除标准
- •Body mass index (BMI) less than 18.00 kg per m2 or greater than 35.00 kg per m2
- •Breastfeeding
- •Life expectancy less than 12 months
- •Eastern Cooperative Oncology Group (ECOG) performance status greater than or equal to 3
- •Unacceptable hepatic function as determined by any of the following: a.
- •Alanine aminotransferase (ALT) greater than or equal to 2X upper limit of normal (ULN) b.
- •Aspartate aminotransferase (AST) greater than or equal to 2X ULN c.
- •Bilirubin greater than or equal to 2X ULN d.
- •Alkaline phosphatase greater than or equal to 2X ULN e.
- •Severe hepatic impairment (Child-Pugh Class C)
- •Unacceptable renal function as determined by any of the following: a.
- •Creatinine greater than or equal to 3X ULN b.
- •Creatinine clearance less than or equal to 30 mL per minute c.
- •Creatinine clearance less than or equal to 60 mL per 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: a.
- •HR greater than 100 BPM b.
- •QRS greater than 120 msec c.
- •QTc greater than 450 msec d.
- •PR greater than 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-scoreless than or equal to -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: a.
- •Estrogen, progesterone, or androgens within 30 days prior to subject’s first visit c.
- •Hormonal contraceptives within 30 days prior to subject’s first visit d.
- •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 22.
结局指标
主要结局
To assess the safety and tolerability of TOL2506 in premenopausal subjects with HR+, HER2-negative breast cancer.
To assess the safety and tolerability of TOL2506 in premenopausal subjects with HR+, HER2-negative breast cancer.
时间窗: NA
次要结局
- 1. Suppression of ovarian function overall (LH, E2, menses; treatments pooled)(Percent of all subjects with LH less than 4 IU per L, E2 less than 20 pg per mL in subjects treated with TOL2506 + endocrine therapy (tamoxifen or aromatase inhibitors) at every measurement from Week 6 to Week 48)
- The occurrences of treatment-emergent adverse events (TEAEs) & serious adverse(events (SAEs))
研究者
Dr Sandeep Singh
CBCC Global Research LLP