Therapeutic Vaccine Plus PD-1 Knockout in Prostate Cancer Treatment

The First Affiliated Hospital of Guangdong Pharmaceutical University

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Prostate Cancer

Treatments: Biological: PD-1 Knockout T Cells; Biological: Therapeutic vaccine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03525652

2018-007

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 30 estimated patients

Sex: Male

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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30 participants in 3 patient groups

Therapeutic vaccine

Active Comparator group

Description:

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.

Treatment:

Biological: Therapeutic vaccine

Therapeutic vaccine plus PD-1 knockout

Experimental group

Description:

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.

Treatment:

Biological: Therapeutic vaccine

Biological: PD-1 Knockout T Cells

PD-1 knockout T cells

Active Comparator group

Description:

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.

Treatment:

Biological: PD-1 Knockout T Cells