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Invasive Bladder Cancer Stage IVPhase 1NCT02863913

PD-1 Knockout Engineered T Cells for Muscle-invasive Bladder Cancer

A Phase 1 study testing PD-1 Knockout T Cells, Cyclophosphamide and IL-2 in people with Invasive Bladder Cancer Stage IV, run by Peking University at 1 site in China.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Invasive Bladder Cancer Stage IV
What is being tested?
PD-1 Knockout T Cells, Cyclophosphamide and IL-2
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
1 siteChina
Study dates
Sep 2016to Sep 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • With other immune diseases, or chronic use of immunosuppressants or steroids
  • Compliance cannot be expected
  • Other conditions requiring exclusion deemed by physician

Trial locations and contacts

1 site in 1 country.

China1 site

  • Department of Urology Peking University First Hospital

    Beijing, Beijing Municipality, 100034

Other trials in China

About this study

Official title: A Dose-escalation Phase I Trial of PD-1 Knockout Engineered T Cells for the Treatment of Muscle-invasive Bladder Cancer

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.

Read the 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.

Being tested
PD-1 Knockout T Cells, Cyclophosphamide, IL-2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PD-1 Knockout T CellsBiological

    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.

  • CyclophosphamideDrug

    Also called cytophosphane

    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-2Drug

    Also called Interleukin-2 (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).

Study groups in NCT02863913
Study groupRoleWhat they receive
Test groupExperimentalPeripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will be knocked out by CRISPR Cas9 in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion. A total of 2 x 10^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third.Interleukin-2 (IL-2) will be given in the following 5 days, 720000 international unit（IU）/Kg/day (if tolerant). Patients will receive a total of 2, 3, 4 cycles of treatment.
Receives: Biological: PD-1 Knockout T Cells; Drug: Cyclophosphamide; Drug: IL-2
Comparable groupPlacebo comparatorPeripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will not be knocked out by CRISPR Cas9 in the laboratory (PD-1 Wild-type T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion. A total of 2 x 10^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Interleukin-2 (IL-2) will be given in the following 5 days, 720000 international unit（IU）/Kg/day (if tolerant).
Receives: Drug: Cyclophosphamide; Drug: IL-2

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Dose Escalation - Approximately 6 months

Secondary outcomes (7)

  1. Response Rate:Response will be evaluated according to RECIST v1.1

    Measured: 90 days

  2. Progression free survival - PFS

    Measured: 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

  3. Overall Survival - OS

    Measured: The time from randomization to death from any cause, assessed up to 2 years

  4. Peripheral blood circulating tumor DNA

    Peripheral circuiting tumor DNA is collected at baseline and 6 weeks after last treatment

    Measured: 6 weeks

  5. Temporal Interleukin-2 change in the peripheral blood

    Measured: Baseline and 1 month and 3 months

  6. Temporal Interferon-γ change in the peripheral blood

    Measured: Baseline and 1 month and 3 months

  7. Temporal Interleukin-6 change in the peripheral blood

    Measured: Baseline and 1 month and 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Aug 2016 (estimated)
  2. Study startSep 2016
  3. Primary completionSep 2019 (estimated)
  4. Study completionSep 2019 (estimated)

Why it stopped: No funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02863913
Sponsor's protocol ID
11007965938
Status last verified
Aug 2016
First submitted
1 Aug 2016
Last updated
6 Mar 2019
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided: plan to share

Publications

  • 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.

    PubMed 27376121

  • Kim J. Immune checkpoint blockade therapy for bladder cancer treatment. Investig Clin Urol. 2016 Jun;57 Suppl 1(Suppl 1):S98-S105. doi: 10.4111/icu.2016.57.S1.S98. Epub 2016 May 26.

    PubMed 27326412

  • Aragon-Ching JB, Trump DL. Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises. Future Oncol. 2016 Sep;12(17):2049-58. doi: 10.2217/fon-2016-0155. Epub 2016 Jun 16.

    PubMed 27306417

  • 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.

    PubMed 27229745

  • Zibelman M, Plimack ER. Systemic therapy for bladder cancer finally comes into a new age. Future Oncol. 2016 Oct;12(19):2227-42. doi: 10.2217/fon-2016-0135. Epub 2016 Jul 12.

    PubMed 27402371

  • Donin NM, Lenis AT, Holden S, Drakaki A, Pantuck A, Belldegrun A, Chamie K. Immunotherapy for the Treatment of Urothelial Carcinoma. J Urol. 2017 Jan;197(1):14-22. doi: 10.1016/j.juro.2016.02.3005. Epub 2016 Jul 25.

    PubMed 27460757

  • 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.

    PubMed 27641687

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PD-1 Knockout T Cells, Cyclophosphamide and IL-2 in people with Invasive Bladder Cancer Stage IV, run by Peking University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 6 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 (time frame: Dose Escalation - Approximately 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02863913, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2019; AzTrials last refreshed its copy on 30 Oct 2026.

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