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

NCT04768608 | Completed Phase 1

• 1 other identifier: 2020-CAR-00CH2
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Castrate-Resistant Prostate Cancer

Keywords

Castrate-Resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Prostate specific antigen (PSA) response rate

  180 days

• Radiographic response rate by RECIST 1.1 & PCWG3

  180 days

• Number of persistent CART cells detected by Quantitative Real-time Polymerase Chain Reaction or flow cytometry

  180 days

Study Arms (1)

PD1-PSMA-CART

EXPERIMENTAL

Patients undergo leukapheresis by receiving cyclophosphamide and fludarabine on days -6 to -4, and then receive PD1-PSMA-CART intravenous injection (IV) at split doses from day 0 on.

Drug: PD1-PSMA-CART cells

Interventions

PD1-PSMA-CART cells DRUG

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

Also known as: Non-viral PD1 integrated anti-PSMA chimeric antigen receptor T cell

PD1-PSMA-CART

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zhejiang University: lead
• Bioray Laboratories: collaborator

Study Sites (1)

The First Affiliated Hospital, Zhejiang University

Hangzhou, Zhejiang, China

Location

Study Officials

• Weijia Fang, MD

  The First Affiliated Hospital, Zhejiang University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Group A: 0.5×10\^6 cells / kg; Group B: 1.0×10\^6 cells / kg; Group C: 2.0×10\^6 cells / kg.

Study Record Dates

• First Submitted: February 18, 2021
• First Posted: February 24, 2021
• Study Start: December 23, 2021
• Primary Completion: June 30, 2022
• Study Completion: May 30, 2023
• Last Updated: July 17, 2023

Record last verified: 2023-07

Locations

CN (1)