Clinical trial NCT02135445: Safety and Efficacy of TAK-385 for Patients With Localized Prostate Cancer
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2014-05-12
Enrollment: 103
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy of TAK-385 for achieving and maintaining testosterone suppression.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Is male, 18 years of age or older.
2. 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:

   1. T2b-T2c disease, or
   2. Gleason score 7, or
   3. Prostate-specific antigen (PSA) 10-20 nanogram per milliliter (ng/mL).
3. Is scheduled for EBRT to begin greater than or equal to (\>=) 12 weeks after the Baseline visit.
4. Has serum testosterone at screening greater then (\>) 150 nanogram per deciliter (ng/dL) (5.2 nanomoles per liter \[nmol/L\]).
5. Has screening serum PSA concentration \>2 ng/mL.
6. Has body mass index (BMI) \>=18.0 at screening or baseline.
7. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening or baseline.
8. 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.).
9. 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.
10. Has suitable venous access for the study-required blood sampling, including pharmacokinetic (PK) and pharmacodynamic sampling.

Exclusion Criteria:

1. Has metastatic disease (based on investigator evaluation and assuming no likely metastatic pelvic lymph nodes \>1.0 cm in long axis diameter).
2. 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.
3. 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.
4. Has abnormal screening and/or baseline laboratory values that suggest a clinically significant underlying disease, or the following laboratory values:

   1. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>1.5 \* institutional upper limit of the normal range (ULN);
   2. Serum creatinine \>2.0 milligram per deciliter (mg/dL);
   3. Total bilirubin \>2.0 \* institutional ULN (unless documented Gilbert's disease);
   4. Uncontrolled diabetes (Hemoglobin A1c \[HbA1c\] \>10 \[percent\] %) or previously undiagnosed diabetes mellitus with HbA1c \>8%.
5. 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.
6. Has electrocardiogram (ECG) abnormalities of:

   1. Q-wave infarction, unless identified 6 or more months before screening;
   2. 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;
   3. 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.
7. Has congenital long QT syndrome.
8. Is currently using Class IA (example, quinidine, procainamide) or Class III (example, amiodarone, sotalol) antiarrhythmic medications.
9. 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.
10. 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).
11. Has received treatment with any investigational products within 3 months before the first dose of study drug.
12. 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.
13. Has known gastrointestinal (GI) disease, condition or procedure that could interfere with the oral absorption or tolerance of TAK-385, including difficulty swallowing tablets.
14. 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-385.
15. Has admission or evidence of alcohol or drug abuse or use of illicit drugs.

Primary outcomes:
measure: Percentage of Participants With Effective Castration Rate Over 25 Weeks
timeFrame: Day 1 Week 5 up to Day 1 Week 25
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs
timeFrame: Baseline up to Week 29
measure: Number of Participants With TEAEs Related to Physical Findings
timeFrame: Baseline up to Week 29
measure: Number of Participants With TEAEs Related to 12-lead Electrocardiogram (ECG) Findings
timeFrame: Baseline up to Week 29
measure: Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Urinalysis
timeFrame: Baseline up to Week 29
measure: Number of Participants Reporting One or More TEAEs and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 29
measure: Average Percent Change in Prostate Size
timeFrame: Baseline, Day 1 Week 9 to Day 1 Week 13
measure: Time to Achieve Effective Castration
timeFrame: Baseline up to Week 37
measure: Time to Achieve Profound Castration
timeFrame: Baseline up to Week 37
measure: Estimated Time to Testosterone Recovery (TTR)
timeFrame: Up to Day 1 Week 37
measure: Percentage of Participants Who Have Recovered to Baseline Value of Testosterone
timeFrame: Up to Day 1 Week 37
measure: Percentage of Participants Who Have Recovered to >280 ng/dL Testosterone
timeFrame: Day 1 Week 25 up to Day 1 Week 37
measure: Number of Participants With PSA Response of >=50% and >=90% Reduction
timeFrame: Day 1 Week 13
measure: Percent Change From Baseline in Serum PSA Concentration
timeFrame: Baseline, Day 1 of Week 2, 3 , 5, 9, 13, 17, 21, 25, 29, 33 and 37
measure: PSA Nadir
timeFrame: Baseline up to Day 1 Week 25
measure: Serum PSA Concentration
timeFrame: Day 1 of Week 13, 25, 29, 33 and 37
measure: Plasma Concentrations of TAK-385
timeFrame: 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
measure: Serum Luteinizing Hormone (LH) Level
timeFrame: Baseline, Day 1 of Weeks 2, 3, 5, 9, 13, 17, 21, 25, 29, and 37
measure: Serum Follicle-Stimulating Hormone (FSH) Level
timeFrame: Baseline, Day 1 of Week 2, 5, 13, 25 and 29
measure: Serum Sex Hormone-Binding Globulin (SHBG) Level
timeFrame: Baseline, Day 1 of Week 2, 5, 13, 25 and 29
measure: Percent Change From Baseline in Aging Male's Symptoms (AMS) Total Scale Score
timeFrame: Day 1 of Weeks 5, 13, 25, 29, 33 and 37
measure: Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) Score
timeFrame: Baseline and last post-baseline value up to Week 37
measure: Change From Baseline in 25-item Prostate Cancer-specific Questionnaire Supplement (EORTC QLQ-PR25) Score
timeFrame: Baseline and last post-baseline value up to Week 37
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: San Diego
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Bradenton
country: United States
state: Florida
city: Daytona Beach
country: United States
state: Florida
city: Fort Lauderdale
country: United States
state: Florida
city: Fort Myers
country: United States
state: Florida
city: Plantation
country: United States
state: Florida
city: Jeffersonville
country: United States
state: Indiana
city: Wichita
country: United States
state: Kansas
city: Shreveport
country: United States
state: Louisiana
city: Omaha
country: United States
state: Nebraska
city: Syracuse
country: United States
state: New York
city: Columbus
country: United States
state: Ohio
city: Eugene
country: United States
state: Oregon
city: Myrtle Beach
country: United States
state: South Carolina
city: Dallas
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Virginia Beach
country: United States
state: Virginia
city: Brighton
country: United Kingdom
state: East Sussex
city: Manchester
country: United Kingdom
state: Greater Manchester
city: Wirral
country: United Kingdom
state: Merseyside
city: Taunton
country: United Kingdom
state: Somerset
city: Sutton
country: United Kingdom
state: Surrey
city: Birmingham
country: United Kingdom
state: West Midlands
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: