Safety and Efficacy of TAK-385 for Patients With Localized Prostate Cancer

Prostate Cancer Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02135445
• Other study ID #: C27003
• Secondary ID: U1111-1152-95372
• Status: Active, not recruiting
• Phase: Phase 2
• First received: May 8, 2014
• Last updated: November 30, 2015
• Start date: June 2014
• Est. completion date: December 2015

Study information

• Verified date: November 2015
• Source: Millennium Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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 external beam radiation therapy (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 ng/mL.

3. Is scheduled for EBRT to begin = 12 weeks after the Baseline visit.

4. Has serum testosterone at screening > 150 ng/dL (5.2 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 (i.e., 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 [e.g., 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 mg/dL;

3. Total bilirubin > 2.0 × institutional ULN (unless documented Gilbert's disease);

4. Uncontrolled diabetes (Hemoglobin A1c [HbA1c] > 10%) 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 (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other significant cardiac condition (e.g., 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 (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 (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications.

9. Has uncontrolled hypertension despite appropriate medical therapy (sitting blood pressure [BP] of greater than 160 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• TAK-385
TAK-385 tablet
• Degarelix
Degarelix injection

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Estimated to have Effective Castration at all Scheduled Visits		during treatment period, within 37 weeks	No
Secondary	Percentage of Participants with Clinically Significant Change from Baseline in Vital Signs		within 37 weeks	Yes
Secondary	Percentage of Participants with Clinically Significant Change from Baseline in Physical Examination Findings		within 37 weeks	Yes
Secondary	Significant Change from Baseline in Electrocardiograms (ECG)		within 37 weeks	Yes
Secondary	Number of Participants With Markedly Abnormal Laboratory Values		within 37 weeks	Yes
Secondary	Number of Participants Reporting One or More Treatment-emergent Adverse Events		within 37 weeks	Yes
Secondary	Average Percent Reduction in Prostate Size		within 8 weeks of starting study drug	No
Secondary	Time to Effective Castration		by end of treatment visit, within 37 weeks	No
Secondary	Time to Profound Effective Castration		by end of treatment visit, within 37 weeks	No
Secondary	Estimated Time to Testosterone Recovery		during 12 weeks off treatment, within 37 weeks	No
Secondary	Estimated Percentage of Participants Who Recovered to Baseline Testosterone Value		during 12 weeks off treatment, within 37 weeks	No
Secondary	Percentage of Participants Who Recovered to > 280 ng/dL Testosterone		during 12 weeks off treatment, within 37 weeks	No
Secondary	Percentage of Participants achieving 90% reduction in Prostate-Specific Antigen (PSA)		within 37 weeks	No
Secondary	Change from Baseline in PSA Response		at 12 weeks	No
Secondary	PSA Nadir (Lowest Level)		during treatment period, within 37 weeks	No
Secondary	Serum PSA Concentration		within 37 weeks	No
Secondary	Plasma Concentration of TAK-385 in Pharmacokinetic (PK) Population		within 37 weeks	No
Secondary	Serum Luteinizing Hormone (LH) in Participants who Receive TAK-385		within 37 weeks	No
Secondary	Serum Follicle-Stimulating Hormone (FSH) in Participants who Receive TAK-385		within 37 weeks	No
Secondary	Serum Sex Hormone-Binding Globulin (SHBG) in Participants who Receive TAK-385		within 37 weeks	No
Secondary	Change From Baseline on Aging Male Symptoms (AMS) Scale		Baseline to Week 37	No
Secondary	Change From Baseline on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30)		Baseline, up to 37 weeks	No
Secondary	Change From Baseline in the 25-item prostate cancer-specific questionnaire supplement (EORTC QLQ-PR25)		Baseline, up to 37 weeks	No