Therapeutic Vaccine Plus PD-1 Knockout in Prostate Cancer Treatment

Phase 1

• Conditions: Prostate Cancer

• Registration Number: NCT03525652
• Lead Sponsor: The First Affiliated Hospital of Guangdong Pharmaceutical University

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.

Study Timeline

• Study Start: 2018-02-22
• Study First Submitted: 2018-04-26
• Status Verified: 2018-05
• Study First Submitted QC: 2018-05-03
• Last Update Submitted: 2018-05-03
• Study First Posted: 2018-05-16
• Last Update Posted: 2018-05-16
• Primary Completion: 2021-02-22
• Study Completion: 2021-08-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (2)

First Affiliated Hospital of Guangdong Pharmaceutical University; 🇨🇳 Guangzhou, Guangdong, China

Professor Size Chen; 🇨🇳 Guangzhou, Guangdong, China