Back to resultsPD1 Integrated Anti-PSMA CART in Treating Patients With Castrate-Resistant Prostate Cancer
Primary Purpose
Castrate-Resistant Prostate Cancer
Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
PD1-PSMA-CART cells
Sponsored by
About this trial
This is an interventional treatment trial for Castrate-Resistant Prostate Cancer focused on measuring Castrate-Resistant Prostate Cancer
Eligibility Criteria
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.
Sites / Locations
- The First Affiliated Hospital, Zhejiang University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PD1-PSMA-CART
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
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
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
Full Information
NCT ID
NCT04768608
First Posted
February 18, 2021
Last Updated
July 14, 2023
Sponsor
Zhejiang University
Collaborators
Bioray Laboratories
1. Study Identification
Unique Protocol Identification Number
NCT04768608
Brief Title
PD1 Integrated Anti-PSMA CART in Treating Patients With Castrate-Resistant Prostate Cancer
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
December 23, 2021 (Actual)
Primary Completion Date
June 30, 2022 (Actual)
Study Completion Date
May 30, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Zhejiang University
Collaborators
Bioray Laboratories
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
PD1-PSMA-CART in Treating Patients With Castrate-Resistant Prostate Cancer
Detailed 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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Castrate-Resistant Prostate Cancer
Keywords
Castrate-Resistant Prostate Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Group A: 0.5×10^6 cells / kg; Group B: 1.0×10^6 cells / kg; Group C: 2.0×10^6 cells / kg.
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PD1-PSMA-CART
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
PD1-PSMA-CART cells
Other Intervention Name(s)
Non-viral PD1 integrated anti-PSMA chimeric antigen receptor T cell
Intervention Description
PD1-PSMA-CART cells will be given IV at split doses
Primary Outcome Measure Information:
Title
Incidence of toxicity graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events
Description
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.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Prostate specific antigen (PSA) response rate
Description
proportion of patients with ≥50% PSA decline from baseline at any time point after therapy and maintained for ≥4weeks
Time Frame
180 days
Title
Radiographic response rate by RECIST 1.1 & PCWG3
Description
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
Time Frame
180 days
Title
Number of persistent CART cells detected by Quantitative Real-time Polymerase Chain Reaction or flow cytometry
Description
Number of persistent CART cells detected by Quantitative Real-time Polymerase Chain Reaction or flow cytometry
Time Frame
180 days
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Weijia Fang, MD
Organizational Affiliation
The First Affiliated Hospital, Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Affiliated Hospital, Zhejiang University
City
Hangzhou
State/Province
Zhejiang
Country
China
12. IPD Sharing Statement
Learn more about this trial
PD1 Integrated Anti-PSMA CART in Treating Patients With Castrate-Resistant Prostate Cancer
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