Phase I clinical trial against castration-resistant prostate cancer (Alpha-PS1 study)

JRCT ID: jRCT2051240038

Registered date:20/05/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Castration-resistant prostate cancer
• Date of first enrollment: 20/05/2024
• Target sample size: 15
• Study type: Interventional
• Intervention(s): Repeated intravenous injection of PSW-1025

Outcome(s)

Primary Outcome

1) Adverse events
Measurement items: Presence / absence, event name, onset date, severity, seriousness, causal relationship with the investigational drug or the investigational medical devices, management of adverse event, outcome, date of outcome or confirmation of outcome
Measurement time: From the administration to 6 months after administration, or at the time of discontinuation
Evaluation Criteria: Japanese translation of CTCAE (Common Terminology Criteria for Adverse Events) 5.0th Edition

2) Dose limiting toxicity (DLT) after single administration
Proportion of the trial subjects with DLT. DLT is defined as the dose of the investigational drug applicable to one or more of the following criteria form the initial administration of the investigational drug to the point of 4 weeks after administration.
(1) Hematological toxicity of Grade 4 or higher regardless of duration
(2) Grade 3 hematological toxicity that lasts for 7 days or more
(3) Febrile or infectious neutropenia of Grade 3 regardless of duration
(4) Thrombocytopenia with bleeding tendency or requiring platelet transfusion
(5) Anemia requiring red blood cell transfusion
(6) Non-hematological toxicity of Grade 3. However, the following are excluded.
- Abnormal laboratory test values which are not clinically significant
- Toxicity that can be controlled to Grade 2 or lower within two days by supportive care
- Due to exacerbation of the underlying disease

Secondary Outcome

1) Safety
(1) Adverse events above the criteria defined in the protocol during repeated administrations.
(2) Vital signs and awareness / objective findings
(3) Clinical test items (blood test, urinalysis, ECG, etc.)

2) Effectiveness assessment
(1) Evaluation of changes in tumor markers (Prostate-Specific Antigen (PSA)) over time
(2) Judgement of tumor shrinkage effect on images

3) Pharmacokinetic
(1) Evaluation of pharmacokinetic parameters
(2) Excretion (urinary, fecal, exhaled)
(3) Scan of distribution in the body and the evaluation of absorbed dose
(4) Effective dose rate (uSv/hr)

Key inclusion & exclusion criteria

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

Include criteria

1) Patients with progressive castration-resistant prostate cancer who meet the following conditions (1) and (2)
(1) Patients with progressive increase of serum Prostate-Specific Antigen (PSA) (>=2ng/mL, three consecutive increases at least one week apart, and two increases of more than 50% from the lowest value), or with the tumor growth or appearance of new lesions detected by imaging studies
(2) Patients with the serum testosterone at castration level (< 50ng/dL)
2) Patients who meet the following conditions (1) and (2), resistant to standard treatment or not indicated for the generally approved standard treatments
(1) Patients who have received at least one of the following treatments
- Inhibitors of androgen receptor signaling (enzalutamide, apalutamide, dalortamide, etc.)
- Inhibitors of Cytochrome P450 17 (CYP 17) (abiraterone acetate)
(2) Patients previously treated with the taxane-based chemotherapy (docetaxel or cabazitaxel) or not adapted for the taxane-based chemotherapy (including refusal cases)*
* Targeting for the patients who have received cabazitaxel therapy after docetaxel therapy, or patients for whom cabazitaxel therapy was not indicated (including refusal cases) after docetaxel therapy, or patients for whom both docetaxel therapy and cabazitaxel therapy were not indicated (including refusal cases)
3) Patients aged 18 years or older at the time of consent acquisition
4) Patients with stable general condition with PS (Performance status) of 0 to 2 in ECOG (Eastern Cooperative Oncology Group)
5) Patients who can be expected to survive for 6 months or more, judging from clinical symptoms and medical examination findings
6) Patients without or with controlled symptomatic brain metastases
7) Patients with no clinically significant abnormal findings in electrocardiogram, respiratory rate, and blood oxygen saturation within 30 days before the enrollment
8) Patients whose laboratory values within 30 days before the enrollment are within the range specified in the protocol
9) Patients who can use appropriate contraception during the clinical trial period according to the protocol
10) Patients who thoroughly listened to the explanation of the clinical trial, agreed to the various study procedures outlined in the clinical trial protocol and signed the consent document

Exclude criteria

1) Patients who received systemic antitumor therapy (e.g. chemotherapy, immunotherapy, biologic therapy such as monoclonal antibodies, excluding androgen receptor signaling inhibitors) within 4 weeks before enrollment
2) Patients who received radium chloride (Radium, 223Ra) or 177Lu (Lutetium)-PSMA-617 within 6 months before registration
3) Patients currently receiving treatment with other cytotoxic chemotherapy, immunotherapy, radioligand therapy, poly ADP-ribose polymerase (PARP) inhibitors, AKT inhibitors
4) Patients with active double cancer (simultaneous double cancer and ectopic double cancer with a disease-free period of 5 years or less)
5) Patients who received other investigational drugs within 5 weeks prior to enrollment
6) Patients with uncontrollable active infections
7) Hepatitis B surface antigen positive, Hepatitis C Virus antibody positive (patients with HCV-RNA level below the limit of detection can be registered) or Human Immunodeficiency Virus antibody positive patients
8) Patients with mental illness or psychiatric symptoms who are judged to be difficult to participate in clinical trials
9) Other patients who are judged to be inappropriate by the investigator, etc.

Related Information

• Primary Sponsor: Watabe Tadashi
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development