Castration-resistant Prostate Cancer, Metastatic Castration-resistant Prostate Cancer
Conditions
Keywords
Castration-resistant Prostate Cancer, Metastasis, Prostate-Specific Membrane Antigen, Chimeric Antigen Receptor T cell, Refractory Castration-resistant Prostate Cancer
Brief summary
This is one center, single-arm, open-label investigator initiated trial to assess the safety and efficacy of enhanced autologous PSMA chimeric antigen receptor T cells in the treatment for patients with refractory castration resistant prostate cancer, and the sample size is set to 7-18 subjects.
Detailed description
This is one center, single-arm, open-label investigator initiated trial to assess the safety and efficacy of enhanced autologous PSMA chimeric antigen receptor T cells in the treatment for patients with refractory castration resistant prostate cancer, and the sample size is set to 7-18 subjects. Based on the "3 + 3" dose escalation design principle, subjects will be divided into 3 groups from low dose to high dose in sequence (Group A; Group B; Group C). Additional subjects will be enrolled into the RP2D group to ensure that 6-9 efficacy-evaluable subjects are available in the RP2D group before entering the phase II study.
Interventions
DRUGEnhanced autologous PSMA-CAR T
3 escalated dosing cohorts are designed to explore safety and efficacy of enhanced autologous PSMA-CAR T: cohort A： CART-PSMA cells 0.25×106/kgBW, following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day given according to protocol; cohort B： CART-PSMA cells 0.75×106/kgBW，following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day given according to protocol; cohort C： CART-PSMA cells 2×106/kgBW，following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day given according to protocol;
Sponsors
Shanghai Changzheng Hospital
Bioray Laboratories
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A：0.25×106/kgBW B: 0.75×106/kgBW C: 2×106/kgBW
Eligibility
Sex/Gender
MALE
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DLT | Within 28 Days After Enhanced autologous PSMA-CAR T Infusion | The number and severity of dose-limiting toxicity (DLT) events |
| The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE V5.0) | Through 6 months after CAR-T cell infusion | Safety assessment: toxicity profile |
| Cytokine Release Syndrome (CRS) grading post CAR T cell infusion | Through 6 months after CAR-T cell infusion | Safety assessment: toxicity profile |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy assessment: PSA changes | 6 months after CAR-T cell infusion | Prostate-Specific Antigen (PSA) changes assessed by serum PSA measurement (ng/ml). |
| Efficacy assessment: radiographic Progression-Free Survival (rPFS) | 3 months after CAR-T cell infusion | rPFS is defined as the time between treatment with study drug and the development of imaging progression or death from any cause, whichever occurs first, with imaging progression encompassing the evaluation of progression of primary lesions, non-regional lymph node invasion, soft tissue metastases, and bone metastatic lesions according to RECIST 1.1 and PCWG3 criteria. |
| Pharmacokinetics (PK) assessment: expansion of CAR-T cells | From Day 1 till at least 3 months after CAR-T cell infusion | With the day of the first infusion of the cellular preparation recorded as DO, the monitoring phase of the pharmacokinetic study started from 1 day before the first infusion (D-1). Expansion of CAR T cells will be assessed by concentration profile of CAR-T cells in peripheral blood after CAR-T infusion. |
| Pharmacokinetics (PK) assessment: persistence of CAR T cells | From Day 1 till at least 3 months after CAR-T cell infusion | With the day of the first infusion of the cellular preparation recorded as DO, the monitoring phase of the pharmacokinetic study started from 1 day before the first infusion (D-1). Persistence of CAR T cells will be assessed by T-cell survival time (area under the curve AUCO-28 at 28 days and area under the curve AUCO-90 at 90 days); |
| Pharmacodynamics (PD) assessment eg. (Level of IL-6) | From Day 1 till at least 3 months after CAR-T cell infusion | Pharmacokinetic (PD) endpoints is assessed by changes in serum cytokine levels (eg.IL-6) after CAR-T infusion. |
Countries
China
Outcome results
None listed