Clinical trial NCT02083185: A Phase 2 Study to Evaluate the Safety and Efficacy of TAK-385, Together With a Leuprorelin Observational Cohort, in Participants With Prostate Cancer
Official title: A Phase 2, Randomized, Open-label, Parallel Group Study to Evaluate the Safety and Efficacy of the Oral GnRH Antagonist TAK-385, Together With a Leuprorelin Observational Cohort, in Patients With Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2014-03-11
Enrollment: 136
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 (\<50 ng/dL).

Detailed description: The drug being tested in this study is called relugolix (TAK-385). Relugolix is being tested to treat people who have prostate cancer. This study will look at achieving and maintaining testosterone suppression (\<50 ng/dL).

The study enrolled 136 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the three treatment groups-which remained undisclosed to the patient and study doctor during the study (unless there was an urgent medical need):

* Relugolix 80 mg
* Relugolix 120 mg
* Leuprorelin 22.5 mg

Relugolix was administered starting with a 320 mg (loading dose), followed by relugolix 80 mg or 120 mg tablets, for 48 weeks plus an optional 48-week extension at the investigator's discretion. Patients randomized to leuprorelin were administered 22.5 mg subcutaneously on Day 1 and every 12 weeks for 4 injections.

This multicenter trial was conducted in the United States and Canada. The overall time to participate in this study was 114.4 weeks. Participants made multiple visits to the clinic and at 12 weeks after last dose of study drug for a follow-up assessment.

Eligibility criteria: Inclusion Criteria

Each participant must meet all of the following inclusion criteria to be enrolled in the study:

1. Male participant 18 years or older.
2. Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma.
3. Candidate for androgen deprivation therapy (ADT) for the management of hormone-sensitive prostate cancer with 1 of the following clinical disease states: 1) advanced localized disease not suitable for primary therapy, 2) evidence of prostate-specific antigen (PSA) biochemical or clinical relapse following primary surgery or radiation therapy of curative intent, or 3) newly diagnosed metastatic disease that is asymptomatic or not threatening to vital organs.
4. Appropriate serum testosterone and serum PSA concentration at screening as specified in the protocol.
5. A body mass index (BMI) ≥ 18.0 at screening and/or baseline.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening and/or baseline.
7. Male participants, even if surgically sterilized, who agree to practice effective barrier contraception or agree to practice true abstinence.
8. Voluntary written consent must be given 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.
9. Suitable venous access for the study-required blood sampling, including pharmacokinetic (PK) and pharmacodynamic (PD) Sampling.

Exclusion Criteria

Participants meeting any of the following exclusion criteria are not to be enrolled in the study:

1. In participants with advanced, localized M0N1 or M1 disease, the presence of clinically significant symptoms or threat to vital organs requiring immediate gonadotropin-releasing hormone (GnRH) /combined or complete androgen blockade (CAB) therapy, chemotherapy, or radiotherapy.
2. Previously received androgen deprivation therapy (ADT) for more than 8 months total duration (if ADT was received for 8 months or less, then that ADT must have been completed at least 2 years prior to screening).
3. Visceral metastases (liver or lung).
4. Features of the participant's medical condition that may make ADT unnecessary or not indicated.
5. Scheduled for additional surgical or (salvage) radiation therapy within 6 months after baseline evaluations.
6. History of surgical castration.
7. Diagnosis of or treatment for another malignancy within the 2 years before the first dose of study drug, or previously diagnosed with another malignancy and have any 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.
8. Abnormal screening and/or baseline laboratory values as specified in the protocol.
9. History of any significant cardiac condition within 6 months before receiving the first dose of study drug.
10. Electrocardiogram (ECG) abnormalities as specified in the protocol
11. Congenital long QT syndrome.
12. Current use of Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications.
13. Uncontrolled hypertension despite appropriate medical therapy. Participants may be re-screened after referral and further management of hypertension.
14. 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).
15. Treatment with any investigational products within 3 months before the first dose of study drug.
16. A primary family member (spouse, parent, child, or sibling of the participant) is involved in the conduct of the study or is a study site employee.
17. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of TAK-385, including difficulty swallowing tablets.
18. Use of any medication, or food products listed in the excluded medications and dietary products table within 2 weeks before the first dose of study drug. Participant must have no history of amiodarone use in the 6 months before the first dose of TAK-385.
19. Admission or evidence of alcohol or drug abuse or use of illicit drugs.

Primary outcomes:
measure: Percentage of Participants With Effective Castration Rate Over 24 Weeks
timeFrame: Day 1 of Week 5 to Day 1 of Week 25
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Vital Signs
timeFrame: From first dose of study drug to 30 days after last dose of study drug up to 106.7 weeks
measure: Number of Participants With TEAEs Related to Physical Examination
timeFrame: From first dose of study drug to 30 days after last dose of study drug up to 106.7 weeks
measure: Number of Participants With TEAEs Related to 12-lead Electrocardiogram (ECG) Findings
timeFrame: From first dose of study drug to 30 days after last dose of study drug up to 106.7 weeks
measure: Number of Participants With TEAES Related to Clinical Laboratory Test Results
timeFrame: From first dose of study drug to 30 days after last dose of study drug up to 106.7 weeks
measure: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From first dose of study drug to 30 days after last dose of study drug up to 106.7 weeks
measure: Percentage of Participants With Prostate-Specific Antigen (PSA) Response of ≥ 50% and ≥ 90% Reduction at 4 Weeks
timeFrame: Week 5, Day 1
measure: Prostate-Specific Antigen Nadir
timeFrame: During Weeks 1 to 24
measure: Serum Prostate-Specific Antigen Concentration at the End of Weeks 12 and 24
timeFrame: Day 1 of Weeks 13 and 25
measure: Time to Achieve Testosterone Concentrations < 50 ng/dL and < 20 ng/dL
timeFrame: During Weeks 1 to 24
measure: TAK-385 Plasma Concentrations
timeFrame: Day 1 of Weeks 1, 2, 3, 5, 9, 13, 17, 25, 37, 49 pre-dose; Day 4 of Week 1 pre-dose; Day 1 of Weeks 5, 13, 2 hrs post-dose
measure: Serum Luteinizing Hormone (LH) Concentrations
timeFrame: Baseline and Day 4 of Week 1, Day 1 of Weeks 2, 3, 5,13, 25 and 49, End of Treatment (EOT - 106.4 Weeks), Follow-up (110.4 Weeks) and End of Study (114.4 Weeks)
measure: Serum Follicle Stimulating Hormone (FSH) Concentrations
timeFrame: Day 1 of Weeks 2, 5, 13, 25, 49, EOT (106.4 Weeks), Follow-up (110.4 Weeks) and End of Study (114.4 Weeks)
measure: Serum Sex Hormone-binding Globulin (SHBG) Concentrations
timeFrame: Day 1 of Weeks 2, 5, 13, 25, 49, EOT (106.4 Weeks), Follow-up (110.4 Weeks) and End of Study (114.4 Weeks)
measure: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-P25 Score
timeFrame: Baseline and Day 1 of Weeks 5,13, 25, 37 and 49, EOT (106.4 Weeks), Follow-up (110.4 Weeks) and End of Study (114.4 Weeks)
measure: Percent Change From Baseline of Aging Male Survey (AMS) Total Score
timeFrame: Baseline and Day 1 of Weeks 5,13, 25, 37 and 49, EOT (106.4 Weeks), Follow-up (110.4 Weeks) and End of Study (114.4 Weeks)
measure: Change From Baseline in EORTC QLQ-C30
timeFrame: Day 1 of Weeks 5, 13, 25, 37, 49, 73, 97, EOT (106.4 Weeks), Follow-up (110.4 Weeks) and End of Study (114.4 Weeks)
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: Daytona Beach
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: Lawrenceville
country: United States
state: New Jersey
city: Garden City
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Springfield
country: United States
state: Oregon
city: Lancaster
country: United States
state: Pennsylvania
city: Myrtle Beach
country: United States
state: South Carolina
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Virginia Beach
country: United States
state: Virginia
city: Abbotsford
country: Canada
state: British Columbia
city: Vancouver
country: Canada
state: British Columbia
city: Montreal
country: Canada
state: Quebec
city: Quebec
country: Canada
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: