Phase II Trial of Endocrine therapy for patients with Metastatic extramammary Paget's disease ExpRessing Androgen-Receptor using Darolutamide with/without LH-RH agonist.

JRCT ID: jRCT2031220508

Registered date:13/12/2022

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Androgen receptor positive advanced stage extramammary Paget's disease
• Date of first enrollment: 13/12/2022
• Target sample size: 40
• Study type: Interventional

Intervention(s)

Cohort 1: 600 mg of darolutamide orally twice daily after meals.
Cohort 2: 600 mg of darolutamide orally twice daily after meals. In addition, goserelin acetate 3.6 mg is injected subcutaneously into the anterior abdomen every 4 weeks.

Outcome(s)

• Primary Outcome: Response rate by central review in patients meeting at least 10% AR incidence

Secondary Outcome

- Response rate by central review
- Response rate by site
- Disease control rate
- Change rate of target lesion
- Maximum change rate of target lesion
- Progression-free survival
- Overall survival
- Duration of response
- Time to response
- Stratified analysis of above
- Adverse events

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Histologically diagnosed extramammary Paget's disease
2) Locally advanced or recurrent/metastatic disease for which curative surgery or radiotherapy is not indicated
3) Androgen receptor expressing tumor cells confirmed by immunohistochemical staining performed by a central laboratory
4) ECOG Performance Status of 0 or 1
5) Laboratory examination within 14 days prior to enrollment meets the given criteria
6) Legally adult at the date of consent
7) One or more measurable diseases as defined in the RECIST Guidelines Version 1.1 on clinical and imaging findings within 14 days prior to enrollment
8) Female patients of childbearing potential who have agreed to use double contraception for at least 28 days after the last dose of the study drug from the time of consent and agreed not to breastfeed for at least 28 days after the last dose of the study drug from the date of consent
9) Male patients who have agreed to use double contraception for at least 90 days after the last dose of the study drug from the date of consent
10) Patients who have given written consent to participate in this study

Exclude criteria

1) Patients who have received the following prior therapies
- Androgen receptor inhibitors
- CYP 17 enzyme inhibitors
- Luteinizing hormone-releasing hormone preparations
2) Patients who used estrogen or 5-alpha reductase inhibitors within 28 days prior to enrollment
3) Patients who received systemic corticosteroids of 10 mg/day or more of prednisolone equivalent within 28 days prior to enrollment
4) Patients who received radiotherapy, excluding irradiation of non-target lesions for symptomatic relief of pain associated with bone metastases, within 12 weeks prior to enrollment
5) Patients with severe or poorly controlled complications or infections
6) Patients with complications which are determined to be inappropriate to enroll by the investigator or subinvestigator
7) Patients with known hypersensitivity to the investigational drug or its components
8) Patients who have received any anti-cancer agent within 28 days prior to enrollment in this study
9) Previous pleurodesis or pericardial adhesionwithin 28 days prior to enrollment
10) Surgery with general anethesia within 28 days prior to enrollment
11) Surgery with local or surface anesthesia within 14 days prior to enrollment
12) Patients who received radiopharmaceuticals, excluding the use for laboratory and diagnostic purposes, within 8 weeks prior to enrollment
13) Patients with a history of stroke, myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass grafting, or congestive heart failure of New York Heart Association Class III or IV within 6 months prior to enrollment
14) Patients with poorly controlled hypertension
15) Patients with gastrointestinal disorders that are expected to significantly impair absorption of the investigational drug or patients who have difficulty taking the investigational drug
16) Patients with active viral hepatitis, active human immunodeficiency virus infection, or chronic liver disease
17) Patients who are not expected to survive for at least 3 months from the date of consent
18) Patients with moderate or severe ascites or pleural effusion
19) Metastasis to the central nervous system
20) Uncontrolled tumor-related pain.
21) Avtive double cancer
22) Pregnant, lactating or patients with a positive pregnancy test
23) Patients participating in clinical trials using any other investigational drugs or medical devices within 30 days prior to enrollment

Related Information

• Primary Sponsor: Nakamura Yoshio
• Secondary Sponsor: Nakamura Yoshio