PD1 Integrated Anti-PSMA CART in Treating Patients With Castrate-Resistant Prostate Cancer

Castrate-Resistant Prostate Cancer Clinical Trial

Official title:

Clinical Trial for the Safety and Efficacy of Non-viral PD1 Integrated Anti-PSMA Chimeric Antigen Receptor T Cells in the Treatment of Refractory Castrate-Resistant Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04768608
• Other study ID #: 2020-CAR-00CH2
• Status: Completed
• Phase: Phase 1
• Start date: December 23, 2021
• Est. completion date: May 30, 2023

Study information

• Verified date: July 2023
• Source: Zhejiang University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

PD1-PSMA-CART in Treating Patients With Castrate-Resistant Prostate Cancer

Description:

Clinical trial for the safety and efficacy of Non-viral programmed cell death protein-1(PD1) integrated anti-prostate-specific-membrane-antigen(PSMA) chimeric antigen receptor T(CART) cells in the treatment of Refractory Castrate-Resistant Prostate Cancer(CRPC)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3
• Est. completion date: May 30, 2023
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Fully understand and voluntarily sign informed consent.

• Aged 18 to 75 years old.

• Expected survival > 6 months.

• CRPC patients:Serum testosterone reached castration level (<50ng/dl or<1.7nmol/L) and:

prostate specific antigen (PSA) increased more than 50% at intervals of one week or three consecutive times, with PSA>2 ng/ml; or imaging scans revealed two or more new lesions or enlargement of soft tissue lesions that met the criteria for evaluating solid tumor response.

• CRPC patients received abiraterone or chemotherapy for 3 months or more, and were ineffective or progressive (PSA continued to rise for 3 months, or bone scan/whole-body imaging showed local recurrence or new metastasis).

• Immunohistochemical staining of repetitive biopsy tissues showed the expression of PSMA in tumor cells was more than 50%.

• Eastern Cooperative Oncology Group (ECOG) score =2.

• Virological examination was negative.

• Hematological indexes: hemoglobin > 100 g/L, platelet count > 100×10^9/L, absolute neutrophil count > 1.5×10^9/L.

Exclusion Criteria:

• Prior treatment with any CART therapy targeting any target.

• Prior treatment with any PSMA targeting therapy.

• Need steroid therapy, except physiological replacement therapy.

• Prior treatment with any immunotherapy, including tumor vaccine therapy, radium-223, checkpoint inhibitors and others.

• Subjects with severe mental disorders.

• Subjects with other malignant tumors.

• Subjects with severe cardiovascular diseases: a, New York Heart Association (NYHA) stage III or IV congestive heart failure; b, history of myocardial infarction or coronary artery bypass grafting (CABG) within 6 months; c, clinical significance of ventricular arrhythmia, or history of unexplained syncope, non-vasovagal or dehydration; d, history of severe non-ischemic cardiomyopathy; e, the left ventricular ejection fraction (left ventricular ejection fraction< 55%) was decreased by echocardiography or multiple gated acquisition scan (within 8 weeks before peripheral blood mononuclear cell (PBMC) collection), and abnormal interventricular septal thickness and atrioventricular size associated with myocardial amyloidosis.

• Patients with ongoing or active infection.

• Organ function: a, Alanine aminotransferase or Aspartate aminotransferase >2.5*Upper limit of normal (ULN); Creatine kinase>1.5*ULN; Creatine kinase isoenzyme >1.5*ULN; Troponin T >1.5*ULN; b, Total bilirubin >1.5*ULN; c, Partial prothrombin time or activated partial thromboplastin time or international standardized ratio > 1.5*ULN without anticoagulant treatment.

• History of participation in other clinical studies within 3 months or treatment with any gene therapy product.

• Intolerant or allergic to cyclophosphamide or fludarabine.

• Subjects not appropriate to participate in this clinical study judged by investigators.

Related Conditions & MeSH terms

• Castrate-Resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• PD1-PSMA-CART cells
PD1-PSMA-CART cells will be given IV at split doses

Locations

Country	Name	City	State
China	The First Affiliated Hospital, Zhejiang University	Hangzhou	Zhejiang

Sponsors (2)

Lead Sponsor	Collaborator
Zhejiang University	Bioray Laboratories

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of toxicity graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events	All adverse events (AEs) will be listed and summarized. Summaries of laboratory data will include, at a minimum, treatment-emergent laboratory abnormalities. Summaries of AEs and laboratory abnormalities will be based on the All Treated analysis set.	28 days
Secondary	Prostate specific antigen (PSA) response rate	proportion of patients with =50% PSA decline from baseline at any time point after therapy and maintained for =4weeks	180 days
Secondary	Radiographic response rate by RECIST 1.1 & PCWG3	Proportion of patients with a best response of either complete response or partial response, assessed using Prostate Cancer Working group3(PCWG3) response criteria & Response Evaluation Criteria In Solid Tumors (RECIST) 1.1	180 days
Secondary	Number of persistent CART cells detected by Quantitative Real-time Polymerase Chain Reaction or flow cytometry	Number of persistent CART cells detected by Quantitative Real-time Polymerase Chain Reaction or flow cytometry	180 days