Clinical trial NCT02863913: PD-1 Knockout Engineered T Cells for Muscle-invasive Bladder Cancer
Official title: A Dose-escalation Phase I Trial of PD-1 Knockout Engineered T Cells for the Treatment of Muscle-invasive Bladder Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Invasive Bladder Cancer Stage IV
Lead sponsor: Peking University
Sponsor class: OTHER
First posted: 2016-08-11
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety of PD-1 knockout engineered T cells in treating metastatic advanced bladder cancer. 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 verified stage IV muscle-invasive bladder 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
* Women at pregnant ages should be under contraception
* 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: Bidnur S, Savdie R, Black PC. Inhibiting Immune Checkpoints for the Treatment of Bladder Cancer. Bladder Cancer. 2016 Jan 7;2(1):15-25. doi: 10.3233/BLC-150026.
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citation: Festino L, Botti G, Lorigan P, Masucci GV, Hipp JD, Horak CE, Melero I, Ascierto PA. Cancer Treatment with Anti-PD-1/PD-L1 Agents: Is PD-L1 Expression a Biomarker for Patient Selection? Drugs. 2016 Jun;76(9):925-45. doi: 10.1007/s40265-016-0588-x.
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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.