Clinical trial NCT03525652: Therapeutic Vaccine Plus PD-1 Knockout in Prostate Cancer Treatment
Official title: Clinical Assessment of a Therapeutic Vaccine in Combination With PD-1 Knockout T Cells in the Treatment of Prostate Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Keywords: Prostate Cancer
Therapeutic vaccine
PD-1 knockout
Lead sponsor: The First Affiliated Hospital of Guangdong Pharmaceutical University
Sponsor class: OTHER
Collaborators: name: Guangzhou Anjie Biomedical Technology Co., Ltd.
name: University of Technology, Sydney
First posted: 2018-05-16
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v4.0
timeFrame: 6 months
Secondary outcomes:
measure: Response Rate
timeFrame: 6 months
measure: Progression free survival - PFS
timeFrame: Up to 12 months
measure: Overall Survival - OS
timeFrame: Death
measure: Peripheral blood circulating tumor DNA
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: First Affiliated Hospital of Guangdong Pharmaceutical University
state: Guangdong
city: Guangzhou
country: China
facility: Professor Size Chen
state: Guangdong
Study officials:
affiliation: The First Affiliated Hospital of Guangdong Pharmaceutical University
name: Size Chen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: