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Metastatic Renal Cell CarcinomaPhase 1NCT02867332

PD-1 Knockout Engineered T Cells for Metastatic Renal Cell Carcinoma.

A Phase 1 study testing PD-1 Knockout T Cells, Cyclophosphamide and IL-2 in people with Metastatic Renal Cell Carcinoma, run by Peking University.

Withdrawn

Withdrawn.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 renal 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
Metastatic Renal Cell Carcinoma
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
No sites listed yet
Study dates
Nov 2016to Nov 2020
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 Renal 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

About this study

Official title: A Dose-escalation Phase I Trial of PD-1 Knockout Engineered T Cells for the Treatment of Metastatic Renal Cell Carcinoma

This study will evaluate the safety of PD-1 knockout engineered T cells in treating metastatic advanced renal 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
Medical subject headings
Carcinoma, Renal Cell

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 NCT02867332
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). Patients will receive a total of 2, 3, 4 cycles of treatment.
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

    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 posted15 Aug 2016 (estimated)
  2. Study startNov 2016
  3. Primary completionNov 2020 (estimated)
  4. Study completionNov 2020 (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
NCT02867332
Sponsor's protocol ID
11007965940
Status last verified
Aug 2016
First submitted
11 Aug 2016
Last updated
6 Mar 2019
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided: plan to do

Publications

  • Gandini S, Massi D, Mandala M. PD-L1 expression in cancer patients receiving anti PD-1/PD-L1 antibodies: A systematic review and meta-analysis. Crit Rev Oncol Hematol. 2016 Apr;100:88-98. doi: 10.1016/j.critrevonc.2016.02.001. Epub 2016 Feb 10.

    PubMed 26895815

  • Koshkin VS, Rini BI. Emerging therapeutics in refractory renal cell carcinoma. Expert Opin Pharmacother. 2016 Jun;17(9):1225-32. doi: 10.1080/14656566.2016.1182987. Epub 2016 May 23.

    PubMed 27112171

  • Hofmann L, Forschner A, Loquai C, Goldinger SM, Zimmer L, Ugurel S, Schmidgen MI, Gutzmer R, Utikal JS, Goppner D, Hassel JC, Meier F, Tietze JK, Thomas I, Weishaupt C, Leverkus M, Wahl R, Dietrich U, Garbe C, Kirchberger MC, Eigentler T, Berking C, Gesierich A, Krackhardt AM, Schadendorf D, Schuler G, Dummer R, Heinzerling LM. Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy. Eur J Cancer. 2016 Jun;60:190-209. doi: 10.1016/j.ejca.2016.02.025. Epub 2016 Apr 13.

    PubMed 27085692

  • Gunturi A, McDermott DF. Potential of new therapies like anti-PD1 in kidney cancer. Curr Treat Options Oncol. 2014 Mar;15(1):137-46. doi: 10.1007/s11864-013-0268-y.

    PubMed 24504486

  • Bockorny B, Dasanu CA. Intrinsic immune alterations in renal cell carcinoma and emerging immunotherapeutic approaches. Expert Opin Biol Ther. 2013 Jun;13(6):911-25. doi: 10.1517/14712598.2013.778970. Epub 2013 Apr 16.

    PubMed 23586712

  • 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 Metastatic Renal Cell Carcinoma, run by Peking University.

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.

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 NCT02867332, which also lists 6 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.

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