NCT02135445已完成2 期
A Phase 2, Randomized, Open-Label, Parallel Group Study Evaluating the Safety and Efficacy of TAK-385, an Oral Gonadotropin-Releasing Hormone (GnRH) Antagonist, for Patients With Localized Prostate Cancer Requiring Neoadjuvant and Adjuvant Androgen Deprivation Therapy With External Beam Radiation Therapy (EBRT)
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 103
- 主要终点
- Percentage of Participants With Effective Castration Rate Over 25 Weeks
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of TAK-385 for achieving and maintaining testosterone suppression.
详细描述
The drug being tested in this study is called TAK-385. Men with prostate cancer benefit from receiving androgen deprivation therapy (ADT) to minimize testosterone levels before, during and after EBRT. This combination increases the potential success of treating their disease. This study will see if TAK-385 [an oral gonadotropin-releasing hormone (GnRH) antagonist] brings testosterone levels down sufficiently, with the convenience and comfort of taking a pill. It will look at the time it takes to restore testosterone levels after radiation therapy as well. One hundred participants will be assigned by chance (like flipping a coin) to a treatment group: 60 to TAK-385, and 40 to degarelix.
Those assigned to TAK-385 will take a daily pill. Those assigned to degarelix will receive an injection under the skin once every four weeks at the clinic. They will start radiation therapy when testosterone is low enough, after at least 12 weeks of treatment. This trial will be conducted at clinics in the United States (US) and United Kingdom (UK). Participants will visit the clinic up to 14 times over 37 weeks for physical exams and blood tests, and might receive one follow-up telephone call.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Is male, 18 years of age or older.
- •Has histologically confirmed diagnosis of localized prostate adenocarcinoma of intermediate risk for which 6-month neoadjuvant and adjuvant androgen deprivation therapy (ADT) to EBRT is indicated. Intermediate risk per National Comprehensive Cancer Network (NCCN) guidelines includes one of the following:
- •T2b-T2c disease, or
- •Gleason score 7, or
- •Prostate-specific antigen (PSA) 10-20 nanogram per milliliter (ng/mL).
- •Is scheduled for EBRT to begin greater than or equal to (>=) 12 weeks after the Baseline visit.
- •Has serum testosterone at screening greater then (>) 150 nanogram per deciliter (ng/dL) (5.2 nanomoles per liter [nmol/L]).
- •Has screening serum PSA concentration >2 ng/mL.
- •Has body mass index (BMI) >=18.0 at screening or baseline.
- •Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening or baseline.
- •Is a male participant, even if surgically sterilized (that is, status postvasectomy), who: Agrees to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or, Agrees to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [example, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.).
- •Has given voluntary written consent before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
- •Has suitable venous access for the study-required blood sampling, including pharmacokinetic (PK) and pharmacodynamic sampling.
排除标准
- •Has metastatic disease (based on investigator evaluation and assuming no likely metastatic pelvic lymph nodes >1.0 cm in long axis diameter).
- •Had prior or current use of a gonadotropin-releasing hormone (GnRH) analog or androgen receptor antagonist as first-line hormone therapy, unless total use was less than 6 months and not more recently than 1 year before the planned baseline visit.
- •Had diagnosis of or treatment for another malignancy within 2 years before the first dose of study drug, or previous diagnosis of another malignancy with evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
- •Has abnormal screening and/or baseline laboratory values that suggest a clinically significant underlying disease, or the following laboratory values:
- •Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >1.5 * institutional upper limit of the normal range (ULN);
- •Serum creatinine >2.0 milligram per deciliter (mg/dL);
- •Total bilirubin >2.0 * institutional ULN (unless documented Gilbert's disease);
- •Uncontrolled diabetes (Hemoglobin A1c [HbA1c] >10 [percent] %) or previously undiagnosed diabetes mellitus with HbA1c >8%.
- •Has history of myocardial infarction, unstable symptomatic ischemic heart disease, any ongoing cardiac arrhythmias of Grade >2 (chronic stable atrial fibrillation on stable anticoagulant therapy is allowed), thromboembolic events (example, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other significant cardiac condition (example, pericardial effusion, restrictive cardiomyopathy) within 6 months before receiving the first dose of study drug.
- •Has electrocardiogram (ECG) abnormalities of:
- •Q-wave infarction, unless identified 6 or more months before screening;
- •Heart rate-corrected QT interval millisecond (msec) (QTcF interval) >480 msec. If QTcF is prolonged in a participant with a pacemaker, the participant may be enrolled in the study upon discussion with the project clinician;
- •If the QTcF interval is 450-480 msec, inclusive, in a participant with current use of medications with known effects on QT interval, the participant may be enrolled in the study following discussion with the project clinician.
- •Has congenital long QT syndrome.
- •Is currently using Class IA (example, quinidine, procainamide) or Class III (example, amiodarone, sotalol) antiarrhythmic medications.
- •Has uncontrolled hypertension despite appropriate medical therapy (sitting blood pressure [BP] of greater than 160 millimeters of mercury (mmHg) systolic and 90 mmHg diastolic at 2 separate measurements no more than 60 minutes apart during the Screening visit). Participants with systolic BP measurements >160 mmHg may be rescreened. Participants with systolic BP measurements 141-160 mmHg, although eligible, should be referred for further management of hypertension if indicated.
- •Has known, previously diagnosed human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C, life-threatening illness unrelated to prostate cancer, or any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with participation in this study. Specific screening for chronic viral illness is at the discretion of the site and/or local institutional review board (IRB).
- •Has received treatment with any investigational products within 3 months before the first dose of study drug.
- •Is a primary family member (spouse, parent, child, or sibling) of anyone involved in the conduct of the study or is a study site employee.
- •Has known gastrointestinal (GI) disease, condition or procedure that could interfere with the oral absorption or tolerance of TAK-385, including difficulty swallowing tablets.
- •Is using any medication or food products listed in the excluded medications and dietary products table within 2 weeks before the first dose of study drug. This list includes moderate and strong inhibitors or inducers of cytochrome P450 (CYP3A4/5) and P-glycoprotein (P-gp). Participants must have no history of amiodarone use in the 6 months before the first dose of TAK-
- •Has admission or evidence of alcohol or drug abuse or use of illicit drugs.
研究组 & 干预措施
TAK-385
Experimental
TAK-385 320 mg, tablets, orally, once, on Day 1, followed by TAK-385 120 mg, orally, once daily for 24 weeks. Each participant may have one upward dose adjustment of 40 mg for efficacy and/or one downward dose adjustment of 40 mg for safety during the study.
干预措施: TAK-385 (Drug)
Degarelix
Active Comparator
Degarelix 240 mg, injection, subcutaneous, on Day 1, followed by degarelix 80 mg, injection, subcutaneous, once every four weeks, for 24 weeks.
干预措施: Degarelix (Drug)
结局指标
主要结局
Percentage of Participants With Effective Castration Rate Over 25 Weeks
时间窗: Day 1 Week 5 up to Day 1 Week 25
Castration rate is defined as the observed percentage of participants who have testosterone concentrations less than (\<) 50 nanogram per deciliter (ng/dL) (1.73 nanomole per liter \[nmol/L\]) at all scheduled visits.
次要结局
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs(Baseline up to Week 29)
- Number of Participants With TEAEs Related to Physical Findings(Baseline up to Week 29)
- Number of Participants With TEAEs Related to 12-lead Electrocardiogram (ECG) Findings(Baseline up to Week 29)
- Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Urinalysis(Baseline up to Week 29)
- Number of Participants Reporting One or More TEAEs and Serious Adverse Events (SAEs)(Baseline up to Week 29)
- Average Percent Change in Prostate Size(Baseline, Day 1 Week 9 to Day 1 Week 13)
- Time to Achieve Effective Castration(Baseline up to Week 37)
- Time to Achieve Profound Castration(Baseline up to Week 37)
- Estimated Time to Testosterone Recovery (TTR)(Up to Day 1 Week 37)
- Percentage of Participants Who Have Recovered to Baseline Value of Testosterone(Up to Day 1 Week 37)
- Percentage of Participants Who Have Recovered to >280 ng/dL Testosterone(Day 1 Week 25 up to Day 1 Week 37)
- Number of Participants With PSA Response of >=50% and >=90% Reduction(Day 1 Week 13)
- Percent Change From Baseline in Serum PSA Concentration(Baseline, Day 1 of Week 2, 3 , 5, 9, 13, 17, 21, 25, 29, 33 and 37)
- PSA Nadir(Baseline up to Day 1 Week 25)
- Serum PSA Concentration(Day 1 of Week 13, 25, 29, 33 and 37)
- Plasma Concentrations of TAK-385(Day 1 Week 1, 2, 3, 5, 9, 13, 17, 25, 33, 37: Pre-dose; Day 1 Week 5, 13: 2 hrs Post-dose; Day 4 Week 1: Pre-dose)
- Serum Luteinizing Hormone (LH) Level(Baseline, Day 1 of Weeks 2, 3, 5, 9, 13, 17, 21, 25, 29, and 37)
- Serum Follicle-Stimulating Hormone (FSH) Level(Baseline, Day 1 of Week 2, 5, 13, 25 and 29)
- Serum Sex Hormone-Binding Globulin (SHBG) Level(Baseline, Day 1 of Week 2, 5, 13, 25 and 29)
- Percent Change From Baseline in Aging Male's Symptoms (AMS) Total Scale Score(Day 1 of Weeks 5, 13, 25, 29, 33 and 37)
- Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) Score(Baseline and last post-baseline value up to Week 37)
- Change From Baseline in 25-item Prostate Cancer-specific Questionnaire Supplement (EORTC QLQ-PR25) Score(Baseline and last post-baseline value up to Week 37)
研究者
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