A Study of TAK-385 in Hormone Treatment-naïve Participants With Prostate Cancer

NCT ID: NCT02141659

Last Updated: 2018-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-01
• Study Completion Date: 2017-04-20

Brief Summary

The purpose of this study is to evaluate the tolerability and safety of TAK-385 in hormone treatment-naïve participants with non-metastatic prostate cancer.

Detailed Description

The objective of this study is to evaluate the tolerability and safety of TAK-385 in hormone treatment-naive participants with non-metastatic prostate cancer. This study consists of two parts: Part A, multiple dose-rising (MRD) phase and Part B, an expansion phase.

Conditions

Hormone Treatment-naïve Participants With Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A Cohort 1: TAK-385 320 mg + TAK-385 80 mg

TAK-385 320 mg loading dose, tablet, orally, once on Day 1, followed by TAK-385 80 mg maintenance dose, tablet, orally, once daily through Days 2 to 28.

Group Type: EXPERIMENTAL

TAK-385

Intervention Type: DRUG

TAK-385 Tablets.

Part A Cohort 2: TAK-385 320 mg + TAK-385 120 mg

TAK-385 320 mg loading dose, tablet, orally, once on Day 1, followed by TAK-385 120 mg maintenance dose, tablet, orally, once daily through Days 2 to 28.

Group Type: EXPERIMENTAL

TAK-385

Intervention Type: DRUG

TAK-385 Tablets.

Part A Cohort 3: TAK-385 320 mg + TAK-385 160 mg

TAK-385 320 mg loading dose, tablet, orally, once on Day 1, followed by TAK-385 160 mg maintenance dose, tablet, orally, once daily through Days 2 to 28.

Group Type: EXPERIMENTAL

TAK-385

Intervention Type: DRUG

TAK-385 Tablets.

Part A Cohort 4: TAK-385 360 mg + TAK-385 120 mg

TAK-385 360 mg loading dose, tablet, orally, once on Day 1, followed by TAK-385 120 mg maintenance dose, tablet, orally, once daily through Days 2 to 28.

Group Type: EXPERIMENTAL

TAK-385

Intervention Type: DRUG

TAK-385 Tablets.

Part B Cohort 1: TAK-385 320 mg + TAK-385 80 mg

TAK-385 320 mg loading dose, tablet, orally, once on Day 1, followed by TAK-385 80 mg maintenance dose, tablet, orally, once daily through Days 2 to 672.

Group Type: EXPERIMENTAL

TAK-385

Intervention Type: DRUG

TAK-385 Tablets.

Part B Cohort 2: TAK-385 320 mg + TAK-385 120 mg

TAK-385 320 mg loading dose, tablet, orally, once on Day 1, followed by TAK-385 120 mg maintenance dose, tablet, orally, once daily through Days 2 to 672.

Group Type: EXPERIMENTAL

TAK-385

Intervention Type: DRUG

TAK-385 Tablets.

Interventions

TAK-385

TAK-385 Tablets.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Participants judged by the investigator to have the capacity to understand the study and follow the study rules.

2. Participants whose written consent (signature or printed name and personal seal on informed consent form) can be obtained before any study procedures are performed.

3. Japanese male participants 20 or more years of age at the time of informed consent.

4. Participants who, if they have a female partner who could become pregnant, agree to practice appropriate means of contraception from the time of informed consent throughout the entire study treatment period and for 4 months after the last dose of study drug.

5. Participants in stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks (28 days) prior to study treatment initiation.

6. Participants with histologically or cytologically confirmed prostate cancer.

7. Participants whose clinical diagnosis is T1-4 N0 M0, or Tx N0 M0 for participants who have undergone radical prostatectomy.

8. Participants who are considered eligible for hormone therapy for prostate cancer.

9. Participants who have not received hormone therapy (example, gonadotropin-releasing hormone [GnRH] agonist, GnRH antagonist, steroidal antiandrogen, non-steroidal androgen) for prostate cancer.

10. Participants who have not undergone surgical castration.

11. Participants with serum testosterone at screening greater than (>) 150 nanogram per deciliter (ng/dL).

12. Participants meeting either of the following criteria for prostate-specific antigen (PSA) at screening. Untreated prostate cancer: PSA at screening > 4.0 nanogram per milliliter (ng/mL) Treated* prostate cancer: PSA at screening > 0.2 ng/mL.

• Participants who have undergone prostatectomy or either or both of high intensity focused ultrasound therapy or radiotherapy (excluding 125I-brachytherapy) prior to the start of this study.

13. Eastern Cooperative Oncology Group (ECOG) Performance Status [17] of 0 or 1.

14. Body mass index (BMI) at screening greater than or equal to (>=) 18.0 kilogram per square meter (kg/m^2).

Exclusion Criteria

1. Participants exhibiting symptoms judged related to prostate cancer by the investigator (example, bone pain, pelvic pain, ureteral obstruction) who urgently require hormone therapy such as GnRH agonist, GnRH antagonist, or CAB/MAB therapy, chemotherapy, or radiotherapy.

2. Participants who have received 5-alpha reductase inhibitors (except for participants who have been treated for male-pattern alopecias).

3. Participants who have received chemotherapy for prostate cancer (including estramustine).

4. Participants who have received 125I-brachytherapy.

5. Participants who received radiotherapy (except for 125I-brachytherapy) within 16 weeks (112 days) before study treatment initiation.

6. Participants who underwent prostatectomy within 16 weeks (112 days before study treatment initiation.

7. Treatment with any investigational compound within the 4 weeks (28 days) prior to the first dose of study drug or ongoing participation in another experimental trial related to the treatment of prostate cancer.

8. Diagnosis or treatment for another systemic malignancy within 2 years before study treatment initiation, or who had received a diagnosis of another malignancy before that and have evidence of residual disease. Participants with non-melanoma skin cancer or carcinoma in situ who have undergone complete resection will not be excluded from the study.

9. Participants taking drugs with moderate to strong cytochrome P450 3A4 (CYP3A4) inhibitory or inducing effects, or any medications, supplements, or food products with P-glycoprotein (P-gp) inhibitory effects, in the 2 weeks (14 days) prior to study treatment initiation.

10. Participants who have received TAK-385 in a past clinical study.

11. Participants for whom it would be difficult to collect blood from a peripheral vein.

12. Participants with uncontrolled and clinically significant nervous, circulatory, pulmonary, hepatic, renal, metabolic, gastrointestinal, urogenital, or endocrine disorders, or other abnormalities (except for the targeted disease) that could affect study participation or the study results. Also, participants meeting any of criteria a through c below.

A. Participants with uncontrolled diabetes (Hemoglobin A1c [HbA1C] > 8 percent [%] at screening). However, participants whose HbA1c is brought under control with diabetes medications may be rescreened.

B. Participants with uncontrolled hypertension (systolic blood pressure > 150 millimeter of mercury (mmHg) and diastolic blood pressure > 90 mmHg at 2 separate measurements taken no more than 60 minutes apart at screening). Participants whose blood pressure is brought under control by antihypertensive medication may be rescreened.

C. Participants with myocardial infarction, unstable symptomatic ischemic heart disease, arrhythmias of common terminology criteria for adverse events (CTCAE) Grade > 2, thromboembolism (deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or other heart diseases (example, pericardial effusion, restrictive cardiomyopathy). However, chronic stable atrial fibrillation controlled by stable anticoagulant therapy will be allowed.

13. Participants with bilateral hydronephrosis or bladder neck outlet obstruction.

14. Known hypersensitivity to TAK-385, TAK-385 excipients, or gonadotropin-releasing hormone (GnRH) antagonists.

15. Participants with a past history of gastrointestinal tract treatments (including gastrectomy) or gastrointestinal disease that could affect the drug absorption or tolerability (malabsorption, esophageal reflux, peptic ulcer, erosive esophagitis).

16. Participants positive for hepatitis B surface antigens (HBsAg), hepatitis C antibodies (HCV), human immunodeficiency virus (HIV) antibodies, or serologic test for syphilis, or with life-threatening disease other than cancer, at screening.

17. Clinically relevant electrocardiogram (ECG) abnormalities, or the following ECG abnormalities, at screening.

• Q-wave infarction, unless identified 6 or more months prior to TAK-385 treatment initiation.
• QTcF interval > 450 millisecond (msec) (when calculating the QTc interval, Fridericia's equation [QT/RR0.33] will be used).

18. Participants with congenital QT prolongation.

19. Current use of Class 1A or Class 3 antiarrhythmic medications.

20. New York Heart Association Class III or IV heart failure.

21. Participants with clinical laboratory abnormalities suggesting clinically relevant underlying disease, or with any of the following abnormal results, at screening.

• Serum creatinine >= 2.0 mg/dL.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >= 1.5*upper limit of normal (ULN) for the study site.
• Total bilirubin >= 2*ULN for the study site.
• Neutrophil count less than (<) 1,500 per cubic millimeter (/mm^3), platelet count < 100,000 per microliter (/mcL), hemoglobin < 10.0 g/dL.
• Results of heart-related tests (creatine kinase MB [CK-MB] and cardiac troponin T) exceeding the study sites reference value.

22. Participants found to have clinical problems on the basis of examination findings, ECG findings, or chest X-ray findings at screening.

23. Participants considered unlikely by investigators to be able to follow the study protocol or considered ineligible for the study by investigators for other reasons.

• Minimum Eligible Age: 20 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Sakura-shi, Chiba, Japan

Maebashi, Gunma, Japan

Sapporo, Hokkaido, Japan

Kanazawa, Ishikawa-ken, Japan

Yokohama, Kanagawa, Japan

Chiyoda-ku, Tokyo, Japan

Countries

Japan

References

Suzuki H, Uemura H, Mizokami A, Hayashi N, Miyoshi Y, Nagamori S, Enomoto Y, Akaza H, Asato T, Kitagawa T, Suzuki K. Phase I trial of TAK-385 in hormone treatment-naive Japanese patients with nonmetastatic prostate cancer. Cancer Med. 2019 Oct;8(13):5891-5902. doi: 10.1002/cam4.2442. Epub 2019 Aug 19.

Reference Type: DERIVED

PMID: 31429205 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1156-6034

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-385/TB-AK160108

Identifier Type: -

Identifier Source: org_study_id