Enhanced PSMA CAR-T treatment for advanced prostate cancer

The Safety and Efficacy Evaluation of Enhanced Autologous PSMA Chimeric Antigen Receptor T Cells in the Treatment of Refractory Castration Resistant Prostate Cancer

This study is testing a new type of CAR-T treatment for men with advanced prostate cancer that hasn't responded to other therapies to see if it can help them.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Male
• Sponsor: Shanghai Changzheng Hospital (other)
• Drugs / interventions: CAR-T, chemotherapy, cyclophosphamide, fludarabine, chimeric antigen receptor
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT06228404 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of enhanced autologous PSMA chimeric antigen receptor T cells in patients with refractory castration-resistant prostate cancer. It is a single-center, open-label trial with a sample size of 7-18 subjects, utilizing a '3 + 3' dose escalation design to assess different dosage levels. Participants will be grouped into three categories based on the dosage received, with additional subjects enrolled to ensure sufficient data for efficacy evaluation before progressing to a phase II study.

Who should consider this trial

Good fit: Ideal candidates are males aged 18-75 with metastatic castration-resistant prostate adenocarcinoma who have experienced disease progression despite standard treatments.

Not a fit: Patients with non-metastatic prostate cancer or those who have not progressed on standard therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced prostate cancer that is resistant to standard treatments.

How similar studies have performed: Other studies using CAR-T cell therapies have shown promising results in various cancers, suggesting potential for success in this novel application.

Eligibility criteria

Inclusion Criteria:

1. Fully understood and voluntarily signed informed consent for this study;
2. male, aged 18-75 years;
3. expected survival of more than 6 months;
4. metastatic castration-resistant prostate adenocarcinoma (CRPC) patients.
5. Receiving CRPC standard treatment (such as new endocrine therapy, chemotherapy and radium-223, etc., one or more of the combination therapy) after the diagnosis of CRPC, ineffective or progressive disease (PSA continued to rise for 3 months, or bone scan/whole-body MRI/PET-CT showed local recurrence or new metastatic lesions, demonstrating disease progression);
6. PSMA expression in tumor cells was positive in immunohistochemical staining of prostate/metastatic biopsy tissue before enrollment;
7. ECOG score \< 2 ;
8. virological examination HAV (hepatitis A virus), HBV (hepatitis B virus), HCV (hepatitis C virus), HIV (human immunodeficiency virus), TP (Treponema pallidum) quantitative detection was negative, (antigen and antibody screening method unknown, confirmed by nucleic acid method); hematological parameters met the following criteria: a. hemoglobin \> 100 g/L; b. platelet count \> 100 × 109/L; c. neutrophils \> 1.5 × 109/L.

Exclusion Criteria:

Subjects meeting any of the following exclusion criteria will be excluded:

1. have received any previous treatment with CAR-T therapy ;
2. have received any previous treatment that targets PSMA;
3. tumor pathology suggests a special type of prostate cancer (e.g., neuroendocrine prostate cancer, etc.)
4. severe mental disorders;
5. suffered from previous malignancies, except for the following: a. basal cell carcinoma or squamous cell carcinoma after standardized treatment; b. having a primary malignancy, but completely resected, with a complete remission time of ≥ 5 years.
6. Subjects with severe cardiovascular disease; a.New York Heart Association (NYHA) stage III or IV congestive heart failure; b.Myocardial infarction ≤ 6 months prior to enrollment or coronary artery bypass graft (CABG); c.Clinically significant ventricular arrhythmia, or history of unexplained syncope, nonvasovagal or not due to dehydration; d.History of severe non-ischemic cardiomyopathy; e.Decreased left ventricular ejection fraction (LVEF \< 55%) as assessed by echocardiogram or multigated acquisition (MUGA) scan, abnormal interventricular septal thickness and atrioventricular size associated with myocardial amyloidosis;
7. active infectious disease or any major infectious event requiring high grade antibiotics;
8. organ function in the following abnormalities: a. serum aspartate aminotransferase or alanine aminotransferase \> 2.5ULN; CK \> ULN; CK-MB \> ULN; TnT \> 1.5ULN; b. total bilirubin \> 1.5ULN; c. partial prothrombin time or activated partial thromboplastin time or international normalized ratio \> 1.5ULN in the absence of anticoagulant therapy;
9. participation in other clinical studies in the past three months or previous treatment with any gene therapy product;
10. intolerance or hypersensitivity to cyclophosphamide and fludarabine chemotherapy;
11. unsuitability to participate in this clinical study in the opinion of the investigator.

Where this trial is running

Shanghai, Shanghai

• Changzheng hospital — Shanghai, Shanghai, China (RECRUITING)

Study contacts

• Study coordinator: Shancheng Ren, MD/PhD

Conditions: Metastatic Castration-resistant Prostate Cancer, Castration-resistant Prostate Cancer, Metastasis, Prostate-Specific Membrane Antigen, Chimeric Antigen Receptor T cell, Refractory Castration-resistant Prostate Cancer