Clinical trial NCT02867345: PD-1 Knockout Engineered T Cells for Castration Resistant Prostate Cancer
Official title: A Dose-escalation Phase I Trial of PD-1 Knockout Engineered T Cells for the Treatment of Castration Resistant Prostate Cancer
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Hormone Refractory Prostate Cancer
Lead sponsor: Peking University
Sponsor class: OTHER
First posted: 2016-08-15
Enrollment: 0
Sex: MALE
Minimum age (years): 45
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Dose Escalation - Approximately 6 months
Secondary outcomes:
measure: Response Rate:Response will be evaluated according to RECIST v1.1
timeFrame: 90 days
measure: Progression free survival - PFS
timeFrame: 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
measure: Overall Survival - OS
timeFrame: The time from randomization to death from any cause, assessed up to 2 years
measure: Peripheral blood circulating tumor DNA
timeFrame: 6 weeks
measure: Temporal Interleukin-2 change in the peripheral blood
timeFrame: Baseline and 1 month and 3 months
measure: Temporal Interferon-γ change in the peripheral blood
timeFrame: Baseline and 1 month and 3 months
measure: Temporal Interleukin-6 change in the peripheral blood
timeFrame: Baseline and 1 month and 3 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of Urology Peking University First Hospital
state: Beijing
Study officials:
References:
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. doi: 10.4161/21624011.2014.963413. eCollection 2014 Nov.
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.
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.
citation: 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. doi: 10.18632/oncotarget.2703.
citation: Yi L, Li J. CRISPR-Cas9 therapeutics in cancer: promising strategies and present challenges. Biochim Biophys Acta. 2016 Dec;1866(2):197-207. doi: 10.1016/j.bbcan.2016.09.002. Epub 2016 Sep 15.