A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY OF EFFICACY AND SAFETY OF ENZALUTAMIDE IN COMBINATION WITH EXEMESTANE IN PATIENTS WITH ADVANCED BREAST CANCER THAT IS ESTROGEN OR PROGESTERONE RECEPTOR-POSITIVE AND HER2-NORMAL
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 247
- 试验地点
- 75
- 主要终点
- Progression Free Survival (PFS): Diagnostic Positive (DX+) Population By Interactive Web Recognition System (IWRS)
研究概览
简要总结
The purpose of this study is to determine if enzalutamide given in combination with exemestane is safe and effective in patients with advanced breast cancer.
详细描述
This is a Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Efficacy and Safety of Enzalutamide in Combination With Exemestane in Patients With Advanced Breast Cancer That Is Estrogen or Progesterone Receptor Positive and HER2-Normal.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Willing and able to provide informed consent;
- •Postmenopausal;
- •Advanced histologically confirmed breast cancer that is ER+, PgR+, or both, and HER-2 normal;
- •Up to one prior hormone therapy and up to one prior chemotherapy in the advanced setting is allowed;
- •Availability of a representative, formalin-fixed, paraffin-embedded tumor specimen that enabled the diagnosis of breast cancer with viable tumor cells in a tissue block or unstained serial slides accompanied bay an associated pathology report;
- •Measurable disease. Patients with non-measurable bone or skin disease as their only manifestation of advanced breast cancer are also eligible;
- •Eastern Cooperative Oncology Group (ECOG) status of 0 or 1;
排除标准
- •Any severe concurrent disease, infection, or comorbid condition that renders the patient inappropriate for enrollment in the opinion of the investigator;
- •Any condition or reason that interferes with the patient's ability to participate in the trial, that may cause undue risk, or complicates the interpretation of safety data, in the opinion of the investigator;
- •Current or previously treated brain metastasis or leptomeningeal disease;
- •Prior therapy (> 28 days) with exemestane in the metastatic setting (Patients receiving exemestane in the adjuvant setting and having disease recurrence more than 1 year after treatment discontinuation are eligible);
- •Requires treatment for tuberculosis or HIV infection;
- •Radiation therapy within 7 days before randomization;
- •History of another invasive cancer within 5 years before randomization;
- •History of seizure or any condition that may predispose to seizure;
- •Clinically significant cardiovascular disease;
- •Active gastrointestinal disorder;
- •Major surgery within 28 days prior to randomization;
- •Treatment with any oral anticancer or with any non-hormonal anticancer agent within 14 days before randomization;
- •Treatment with any approved or investigational agent that blocks androgen synthesis or targets the androgen receptor;
- •Treatments with any of the following medications within 14 days before randomization: Estrogens, Androgens, or Systemic radionuclides;
- •Hypersensitivity reaction to exemestane.
研究组 & 干预措施
Enzalutamide & exemestane
Enzalutamide 160 mg/day administered as four 40mg soft gelatin capsules by mouth once daily with or without food and exemestane 50mg (two 25mg tablets overencapsulated as a single capsule during the blinded portion of the study and two 25mg tablets after unblinding) once daily after food.
干预措施: Enzalutamide (Drug)
Enzalutamide & exemestane
Enzalutamide 160 mg/day administered as four 40mg soft gelatin capsules by mouth once daily with or without food and exemestane 50mg (two 25mg tablets overencapsulated as a single capsule during the blinded portion of the study and two 25mg tablets after unblinding) once daily after food.
干预措施: exemestane (Drug)
Placebo & exemestane
Placebo and exemestane 25mg (overencapsulated to match 50mg dose during the blinded portion of the study and one 25mg tablet without placebo after unblinding) once daily after food.
干预措施: exemestane (Drug)
Placebo & exemestane
Placebo and exemestane 25mg (overencapsulated to match 50mg dose during the blinded portion of the study and one 25mg tablet without placebo after unblinding) once daily after food.
干预措施: Placebo (for enzalutamide) (Drug)
结局指标
主要结局
Progression Free Survival (PFS): Diagnostic Positive (DX+) Population By Interactive Web Recognition System (IWRS)
时间窗: From randomization until PD, last tumor assessment without PD before new antitumor treatment initiation or death due to any cause, whichever occurred first (up to 3 years)
PFS was defined as the time in months from randomization to the first documentation of PD or death on study due to any cause, whichever occurred first. PD according to RECIST 1.1, was defined as \>= 20% increase in the sum of diameters of the target lesions taking as a reference the smallest sum recorded since the start of treatment or unequivocal progression in non-target lesions or the appearance of 1 or more new lesions. The analysis of PFS was based on investigator assessment of disease progression. Participants who were not known to have had a PFS event at the analysis date were censored at last tumor assessment date prior to data cutoff or date of new treatment initiation, whichever occurred first.
Progression Free Survival (PFS): Intent-to-Treat (ITT) Population By Interactive Web Recognition System (IWRS)
时间窗: From randomization until PD, last tumor assessment without PD before new antitumor treatment initiation or death due to any cause, whichever occurred first (up to 3 years)
PFS was defined as the time in months from randomization to the first documentation of progression of disease (PD) or death on study due to any cause, whichever occurred first. PD according to response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) was defined as greater than or equal to (\>=) 20 percent (%) increase in the sum of diameters of the target lesions taking as a reference the smallest sum recorded since the start of treatment or unequivocal progression in non-target lesions or the appearance of 1 or more new lesions. The analysis of PFS was based on investigator assessment of disease progression. Participants who were not known to have had a PFS event at the analysis date were censored at last tumor assessment date prior to data cutoff or date of new treatment initiation, whichever occurred first.
次要结局
- Clinical Benefit Rate-24 (CBR-24)(From randomization up to 3 years)
- Concentration Versus Time Summary of Exemestane(Predose, 1 and 6 hour postdose on Day 29, 57, 113 and 169)
- Best Objective Response Rate(From randomization until CR or PR, whichever occurred first (up to 3 years))
- Time to Progression(From randomization until PD or last tumor assessment without PD before new antitumor treatment initiation, whichever occurred first (up to 3 years))
- Duration of Objective Response(From first documentation of CR or PR until PD, or last tumor assessment without PD before new antitumor treatment initiation or death due to any cause, whichever occurred first (up to 3 years))
- Progression Free Survival (PFS) at 6 Months(Month 6)
- Concentration Versus Time Summary of Enzalutamide(Predose on Day 29, 57 and 113)
- Time to Response(From randomization until first documentation of CR or PR, or last tumor assessment without PD or death prior to new antitumor treatment initiation, whichever occurred first (up to 3 years))
- Concentration Versus Time Summary of N-desmethyl Enzalutamide(Predose on Day 29, 57 and 113)