Castrate-Resistant Prostate Cancer
Conditions
Keywords
Castrate-Resistant Prostate Cancer
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)
Interventions
DRUGPD1-PSMA-CART cells
PD1-PSMA-CART cells will be given IV at split doses
Sponsors
Bioray Laboratories
Zhejiang University
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
MALE
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of toxicity graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events | 28 days | 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
| Measure | Time frame | Description |
|---|---|---|
| Prostate specific antigen (PSA) response rate | 180 days | 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 | 180 days | 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 | 180 days | Number of persistent CART cells detected by Quantitative Real-time Polymerase Chain Reaction or flow cytometry |
Countries
China
Outcome results
None listed