PD-1 Knockout Engineered T Cells for Castration Resistant Prostate Cancer

Hormone Refractory Prostate Cancer Clinical Trial

Official title:

A Dose-escalation Phase I Trial of PD-1 Knockout Engineered T Cells for the Treatment of Castration Resistant Prostate Cancer

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02867345
• Other study ID #: 11007965939
• Status: Withdrawn
• Start date: November 2016
• Est. completion date: December 2020

Study information

• Verified date: August 2016
• Source: Peking University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study will evaluate the safety of PD-1 knockout engineered T cells in treating castration resistant prostate cancer (CRPC). Blood samples will also be collected for research purposes.

Description:

This is a dose-escalation study of ex-vivo knocked-out, expanded, and selected PD-1 knockout-T cells from autologous origin. Patients are assigned to 1 of 3 treatment groups to determine the maximal tolerant dose. After the lower number of cycles are considered tolerant, an arm of the next higher number of cycles will be open to next patients. Biomarkers and immunological markers are collected and analyzed as well.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2020
• Est. primary completion date: November 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 45 Years to 85 Years

Eligibility

Inclusion Criteria:

• Pathologically and clinical verified castration resistant prostate cancer with measurable lesions (On CT: longest diameter of tumoral lesion >=10 mm, shorted diameter of lymph node >=15 mm; measurable lesions should not have been irradiated)

• Progressed after all standard treatment

• Performance score: 0-1

• Expected life span: >= 6 months

• Toxicities from prior treatment has resolved. Washout period is 4 weeks for chemotherapy, and 2 weeks for targeted therapy

• Major organs function normally

• Willing and able to provide informed consent

Exclusion Criteria:

• Pathology is mixed type

• Emergent treatment of tumor emergency is needed

• Poor vasculature

• Coagulopathy, or ongoing thrombolytics and/or anticoagulation

• Blood-borne infectious disease, e.g. hepatitis B

• History of mandatory custody because of psychosis or other psychological disease inappropriate for treatment deemed by treating physician

• With other immune diseases, or chronic use of immunosuppressants or steroids

• Compliance cannot be expected

• Other conditions requiring exclusion deemed by physician

Related Conditions & MeSH terms

• Hormone Refractory Prostate Cancer
• Prostatic Neoplasms

Intervention

Biological:
• PD-1 Knockout T Cells
PD-1 Knockout T Cells and PD-1 wild-type T Cells will be made by Cell Biotech Co., Ltd. 2x107/kg T cells will be used for test group and comparable group separately.

Drug:
• Cyclophosphamide
Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion. Interleukin-2 (IL-2) will be given in the following 5 days, 720000 international unit(IU)/Kg/day (if tolerant).
• IL-2
Interleukin-2 (IL-2) will be given in the following 5 days after cell infusion, 720000 international unit(IU)/Kg/ day (if tolerant).

Locations

Country	Name	City	State
China	Department of Urology Peking University First Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University

Country where clinical trial is conducted

China, 

References & Publications (4)

Bishop JL, Sio A, Angeles A, Roberts ME, Azad AA, Chi KN, Zoubeidi A. PD-L1 is highly expressed in Enzalutamide resistant prostate cancer. Oncotarget. 2015 Jan 1;6(1):234-42. — View Citation

Modena A, Ciccarese C, Iacovelli R, Brunelli M, Montironi R, Fiorentino M, Tortora G, Massari F. Immune Checkpoint Inhibitors and Prostate Cancer: A New Frontier? Oncol Rev. 2016 Apr 15;10(1):293. doi: 10.4081/oncol.2016.293. eCollection 2016 Apr 15. Revi — View Citation

Taube JM. Unleashing the immune system: PD-1 and PD-Ls in the pre-treatment tumor microenvironment and correlation with response to PD-1/PD-L1 blockade. Oncoimmunology. 2014 Dec 21;3(11):e963413. eCollection 2014 Nov. — View Citation

Yatsuda J, Eto M. [Current status and prospects of immunotherapy for castration-resistant prostate cancer]. Nihon Rinsho. 2014 Dec;72(12):2174-8. Japanese. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Adverse Events and/or Dose Limiting Toxicities as a Measure of Safety and tolerability of dose of PD-1 Knockout T cells using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients		Dose Escalation - Approximately 6 months
Secondary	Response Rate:Response will be evaluated according to RECIST v1.1		90 days
Secondary	Progression free survival - PFS		From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to average 10 months
Secondary	Overall Survival - OS		The time from randomization to death from any cause, assessed up to 2 years
Secondary	Peripheral blood circulating tumor DNA		6 weeks
Secondary	Temporal Interleukin-2 change in the peripheral blood		Baseline and 1 month and 3 months
Secondary	Temporal Interferon-? change in the peripheral blood		Baseline and 1 month and 3 months
Secondary	Temporal Interleukin-6 change in the peripheral blood		Baseline and 1 month and 3 months