Castration-resistant Prostate Cancer, Metastatic Castration-resistant Prostate Cancer, Metastatic Prostate Cancer
Conditions
Keywords
Prostate cancer, Universal CAR-T, Metastatic Castration-resistant Prostate Cancer, Chimeric Antigen Receptor T cell
Brief summary
This is a single-arm, single-center, open-label clinical trial designed to evaluate the clinical safety and tolerability of different doses of Prostate-Specific Membrane Antigen (PSMA)-Universal Chimeric Antigen Receptor (UCAR) T-lymphocytes (PSMA-UCAR T) for the treatment of patients with refractory castration-resistant prostate cancer (CRPC).
Detailed description
This is a single-arm, single-center, open-label clinical trial, which aims to evaluate safety and clinical efficacy of different doses of PSMA-UCAR T (BRL-302) in treating patients with refractory CRPC. Three patients will be firstly enrolled at a dose level (DL) of 5.0 × 10\^6cells/kg in the DL1 group. Based on preliminary safety data, efficacy information, and PK/PD parameters obtained at DL1 cohort, the investigator may enroll another three patients in a decreased dose level group of DL-2: 3 × 10\^6 cells/kg or DL-1:1 × 10\^6 cells/ kg, after thorough discussions between the investigators.
Interventions
BIOLOGICALPSMA-UCAR T (BRL-302)
Three patients will be firstly enrolled at a dose level (DL) of 5.0 × 10\^6cells/kg in the DL1 group, following lymphodepleting chemotherapy which will be given under instruction of protocol and investigators' assessment; Based on preliminary safety data, efficacy information, and PK/PD parameters obtained at DL1 cohort, the investigator may enroll another three patients in a decreased dose level group of DL-2: 3 × 10\^6 cells/kg or DL-1:1 × 10\^6 cells/ kg, after thorough discussions between the investigators.
Sponsors
Shanghai Changzheng Hospital
Bioray Laboratories
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Fully understood and voluntarily signed informed consent for this study; 2. Male, aged 18-80 years; 3. Expected survival of more than 6 months; 4. Metastatic castration-resistant prostate adenocarcinoma (CRPC) patients: Have received CRPC standard treatment (such as novel hormone therapies, chemotherapy and radium-223, etc., one or more of the combination therapy) after the diagnosis of CRPC, and is ineffective or progressive :PSA continued rising for 3 months, or bone scan/whole-body MRI/PET-CT showed local recurrence or new metastatic lesions, demonstrating disease progression; 5. PSMA expression in tumor cells was positive in immunohistochemical staining of prostate/metastatic biopsy tissue before enrollment (within 6 months prior to enrollment); 6. ECOG score \< 2 ; 7. 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); 8. Hematological parameters met the following criteria: a. hemoglobin \> 100 g/L; b. platelet count \> 100 × 10\^9/L; c. neutrophils \> 1.5 × 10\^9/L.
Exclusion criteria
Subjects meeting any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Safety assessment: dose-limiting toxicity | 28 days after CAR T cell infusion | Incidence of dose-limiting toxicity (DLT) within 28 days. Dose-limiting toxicity (DLT) is defined as any relevant adverse event that ≥ grade 3 and did not resolve to a grade ≤ grade 2 within 28 days after the first infusion back. |
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) | 6 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. |
| 6-months Progression-Free Survival (PFS) | 6 months after CAR T cell infusion | PFS is defined as the time between treatment with study drug and disease progression or death from any cause, whichever occurs first, including biochemical progression or radiographic progression after evaluation according to RECIST 1.1 and PCWG3 criteria according to the included. |
| 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 D0, 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 PSMA-UCAR 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 D0, 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 AUC0-28 at 28 days and area under the curve AUC0-90 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 PSMA-UCAR T infusion. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORShancheng Ren, MD, PhD
Shanghai Changzheng Hospital
Outcome results
None listed