Therapeutic Vaccine Plus PD-1 Knockout in Prostate Cancer Treatment

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

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.

Study Overview

• Status: Unknown
• Conditions: Prostate Cancer
• Intervention / Treatment: Biological: Therapeutic vaccine; Biological: PD-1 Knockout T Cells

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Zhizhou Huang, MSc; Phone Number: +8613268258980; Email: hzhizhou@sina.com
• Study Contact Backup: Name: Size Chen, MD, PhD; Phone Number: +8613710956393; Email: 13710956393@139.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • First Affiliated Hospital of Guangdong Pharmaceutical University
      • Contact: Guobiao Huang; Phone Number: 86-20-39352064; Email: 153706227@qq.com
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • Professor Size Chen
      • Contact: Zhizhou Huang, MSc; Phone Number: +8613268258980; Email: hzhizhou@sina.com
      • Contact: Size Chen, MD,PhD; Phone Number: +8613720956393; Email: 13720956393@139.com
      • Principal Investigator: Yiguang Lin, MD, PhD
      • Principal Investigator: Size Chen, MD, PhD
      • Sub-Investigator: Micheal Yin, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Therapeutic vaccine; 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; 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.
Experimental: Therapeutic vaccine plus PD-1 knockout; 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; 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.; Biological: PD-1 Knockout T Cells; 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.
Active Comparator: PD-1 knockout T cells; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Guangdong Pharmaceutical University
• Collaborators: University of Technology, Sydney; Guangzhou Anjie Biomedical Technology Co., Ltd.
• Investigators: Principal Investigator: Size Chen, MD, PhD, The First Affiliated Hospital of Guangdong Pharmaceutical University

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2018
• Primary Completion (Anticipated): February 22, 2021
• Study Completion (Anticipated): August 30, 2021

Study Registration Dates

• First Submitted: April 26, 2018
• First Submitted That Met QC Criteria: May 3, 2018
• First Posted (Actual): May 16, 2018

Study Record Updates

• Last Update Posted (Actual): May 16, 2018
• Last Update Submitted That Met QC Criteria: May 3, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Prostate Cancer; Therapeutic vaccine; PD-1 knockout
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 2018-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No