Therapeutic Vaccine Plus PD-1 Knockout in Prostate Cancer Treatment

Study Overview
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Brief Summary
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This study is to evaluate the safety and efficacy of a therapeutic vaccine in combination with PD-1 knockout T cells in the treatment of advanced prostate cancer.

Detailed Description
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This is a phase 1/2 clinical study investigating the safety and efficacy of a therapeutic vaccine in combination with PD-1 knockout T cells in the treatment of advanced prostate cancer. The therapeutic vaccine is a customized product involving ex vivo treatment of the patient's peripheral blood mononuclear cells with a recombinant fusion protein (PAP-GM-CSF) to activate the expression of the antigen that would activate the immune function to kill cancer cells. The PD-1 knockout engineered T cells are also prepared using patient's T cells in which PD-1 gene will be knocked out using CRISPR Cas9 technology. The therapeutic vaccine and PD-1 knockout T cells will be infused back to the patient in 3 times with a 2-week interval.

Official Title
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Clinical Assessment of a Therapeutic Vaccine in Combination With PD-1 Knockout T Cells in the Treatment of Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Biological: Therapeutic vaccine
* Biological: PD-1 Knockout T Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Histologically confirmed prostate cancer (stage IV, according to NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer, Version 2.2017) Evidence of metastasis in the soft tissue and/or bone. Progressive androgen independent castrate resistant prostate cancer. Serum PSA ≥ 5.0 ng/mL Estimated life expectancy ≥ 6 months. Castrate level of testosterone (< 50 ng/dL) achieved via medical or surgical castration. Adequate hematologic, renal and liver function. Exclusion Criteria: • Presence of known lung, liver, or brain metastases, malignant pleural effusions, or malignant ascites. Presence of moderate to severe pain treating with opioid analgesics within 21 days prior to registration. ECOG score ≥ 2. Any other systemic therapy for prostate cancer (except for medical castration). Participation in previous study using Provenge (Sipuleucel-T) or similar product. Known pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%) or spinal cord compression. Known malignancies other than prostate cancer requiring active treatment within 6 months. A requirement for systemic immunosuppressive therapy for any reason. A history of allergic reactions attributed to compounds of similar chemical or biologic composition to this product or granulocyte-macrophage colony-stimulating factor. Any infection requiring parenteral antibiotic therapy or causing fever (temp > 100.5°F or > 38.1°C) within 1 week prior to registration. Any medical intervention or other condition which, in the opinion of the Principal Investigator could compromise adherence with study requirements or otherwise compromise the study's objectives. Treatment with any of the following medications or interventions within 28 days of registration: Systemic use of corticosteroids, External beam radiation therapy or surgery, Use of non-steroidal antiandrogens Dietary and herbal supplements, as well as alternative treatments that have evidence of hormonal and/or anticancer properties (e.g., prostate cancer (PC) -SPES or PC-SPEC) and saw palmetto, Megestrol acetate (Megace®), diethylstilbesterol (DES), or cyproterone acetate, ++Ketoconazole, 5-alpha-reductase inhibitors, Treatment with any other investigational product Treatment with chemotherapy High dose calcitriol [1,25(OH)2Vitamin D] (i.e., > 0.5 mcg/day). Initiation or discontinuation of bisphosphonate therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Therapeutic vaccine<br>Therapeutic vaccine will be prepared ex vivo using the peripheral mononuclear cells from the patients and the vaccine (as maturated dendritic cells) will be infused back to the patients in 3 times with a 2-week interval. | Biological: Therapeutic vaccine<br>* The therapeutic vaccine will be custom prepared ex vivo using the peripheral mononuclear cells from the patient and the vaccine which presented as maturated dendritic cells will be infused back to the patients in 3 times.<br>|
| Experimental: Therapeutic vaccine plus PD-1 knockout<br>Therapeutic vaccine and PD-1 knockout T cells will be prepared ex vivo using the white cells from the patients and the vaccine (as maturated dendritic cells) and maturated PD-1 knockout T cells will be infused back to the patients in 3 times. | Biological: Therapeutic vaccine<br>* The therapeutic vaccine will be custom prepared ex vivo using the peripheral mononuclear cells from the patient and the vaccine which presented as maturated dendritic cells will be infused back to the patients in 3 times.<br>Biological: PD-1 Knockout T Cells<br>* PD-1 knockout T cells will be custom prepared ex vivo using the white blood cells from the patient and the maturated PD-1 knockout T cells will be infused back to the patients in 3 times.<br>|
| Active Comparator: PD-1 knockout T cells<br>PD-1 knockout T cells will be prepared ex vivo using the white cells from the patients and the maturated PD-1 knockout T cells will be infused back to the patients in 3 times. | Biological: PD-1 Knockout T Cells<br>* PD-1 knockout T cells will be custom prepared ex vivo using the white blood cells from the patient and the maturated PD-1 knockout T cells will be infused back to the patients in 3 times.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v4.0 | Safety and tolerability of dose of therapeutic vaccine in combination with PD-1 Knockout T cells will be assessed using CTCAE v4.0 | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Will be assessed according to the revised RECIST guideline v1.1 | 6 months | 
| Progression free survival - PFS | Time from treatment to date of first documented progression or date of death | Up to 12 months | 
| Overall Survival - OS | Measure the time from the commencement of treatment to death | Death | 
| Peripheral blood circulating tumor DNA | Circuiting tumor DNA will be measured at baseline and 6 weeks after treatment | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer, Therapeutic vaccine, PD-1 knockout