Therapeutic Vaccine Plus PD-1 Knockout in Prostate Cancer Treatment

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03525652
• Other study ID #: 2018-007
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 22, 2018
• Est. completion date: August 30, 2021

Study information

• Verified date: May 2018
• Source: The First Affiliated Hospital of Guangdong Pharmaceutical University
• Contact: Size Chen, MD, PhD
• Phone: +8613710956393
• Email: 13710956393[@]139.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: August 30, 2021
• Est. primary completion date: February 22, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	First Affiliated Hospital of Guangdong Pharmaceutical University	Guangzhou	Guangdong
China	Professor Size Chen	Guangzhou	Guangdong

Sponsors (3)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Guangdong Pharmaceutical University	Guangzhou Anjie Biomedical Technology Co;LTD, University of Technology, Sydney

Country where clinical trial is conducted

China, 

Outcome

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