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Metastatic Urothelial CancerPhase 1NCT02826564

Trial of Stereotactic Body Radiotherapy With Concurrent Pembrolizumab in Metastatic Urothelial Cancer

A Phase 1 study testing pembrolizumab in people with Metastatic Urothelial Cancer, run by University Hospital, Ghent at 1 site in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The goal of the proposed research project is to assess the safety (dose limiting toxicity, DLT) of the combination of pembrolizumab and high-dose stereotactic body radiotherapy (SBRT) in patients with metastatic urothelial cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Urothelial Cancer
What is being tested?
pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteBelgium
Study dates
14 Nov 2016to 18 Feb 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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Be willing and able to provide written informed consent/assent for the trial.
  • Be ≥ 18 years of age on day of signing informed consent.
  • Have measurable disease based on RECIST 1.1.
  • Have had any prior treatment more than 2 weeks prior to study day 1, treatment naïve patients are allowed
  • Histologically confirmed diagnosis of urothelial carcinoma
  • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.
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  • Have a performance status of 0 or 1 on the ECOG Performance Scale.
  • Demonstrate adequate organ function, all screening labs should be performed within 10 days before treatment initiation.
  • (Adequate organ function: Absolute neutrophil count (ANC) ≥1,500 /mcL, Platelets ≥100,000 / mcL, Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment), Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN, Serum total bilirubin ≤ 1.5 X ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN, AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases, Albumin >2.5 mg/dL, International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy (as long as PT or PTT is within therapeutic range of intended use of anticoagulants ≤1.5 X ULN unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants a Creatinine clearance should be calculated per institutional standard)
  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Female subjects of childbearing potential (Section 5.7.2) must be willing to use an adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the course of the study through 120 days after the last dose of study medication.
  • Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate method of contraception as outlined in Section 5.7.1- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  • Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Who cannot join

  • The subject must be excluded from participating in the trial if the subject:
  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  • Has had radiotherapy interfering with SBRT.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  • Has a known history of active TB (Bacillus Tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients.
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  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
  • Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
  • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has known history of, or any evidence of active, non-infectious pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

Trial locations and contacts

1 site in 1 country.

Belgium1 site

  • University Hospital Ghent

    Ghent, 9000

Other trials in Belgium

About this study

Official title: Phase I Trial of Stereotactic Body Radiotherapy With Concurrent Pembrolizumab in Metastatic Urothelial Cancer

The goal of the proposed research project is to assess the safety (dose limiting toxicity, DLT) of the combination of pembrolizumab and high-dose stereotactic body radiotherapy (SBRT) in patients with metastatic urothelial cancer. Both the SBRT dose and pembrolizumab dose will be fixed, but the timing of the combination will be varied. Secondary objectives include response rates, local control, progression-free survival (PFS) and overall survival (OS). Exploratory endpoints include immunologic responses and response rates in PD-L1- TIL- tumors. The combination sequence with the most promising response rates and the best safety profile will be selected to continue in a Phase II trial.

Being tested
pembrolizumab
Keywords
radiotherapy, immunotherapy

What participants receive

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

Study groups in NCT02826564
Study groupRoleWhat they receive
SequentialExperimentalStereotactic body radiotherapy prior to pembrolizumab treatment
Receives: Drug: pembrolizumab
ConcurrentExperimentalStereotactic body radiotherapy concurrent with pembrolizumab treatment
Receives: Drug: pembrolizumab

What is being measured

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

  1. Selection of the sequence arm with a DLT < 20% based on the incidence of treatment-related adverse events

    Toxicities will be considered as DLT if occurring between the start of SBRT and 12 weeks after completion of SBRT. DLT will be assessed using the Common Terminology Criteria for Adverse Events.

    Measured: 12 weeks post-radiotherapy

Secondary outcomes (2)

  1. Tumor response

    Response rate of non-irradiated lesions will be evaluated as per RECIST v1.1 and per immune related response criteria (irRC) (Wolchok et al Clinical Cancer Research 2009)

    Measured: 12 weeks

  2. Immunologic response in peripheral blood

    Immunologic responses will be assessed using peripheral blood samples, analyzed with FACS phenotyping, functional testing and ELISA

    Measured: 12 weeks

Timeline

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

  1. First posted11 Jul 2016 (estimated)
  2. Study start14 Nov 2016
  3. Primary completion2 Apr 2018
  4. Study completion18 Feb 2019

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02826564
Sponsor's protocol ID
EC/2016/0661 (BC-00197)
Status last verified
Jul 2024
First submitted
29 Jun 2016
Last updated
17 Jul 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Sundahl N, Vandekerkhove G, Decaestecker K, Meireson A, De Visschere P, Fonteyne V, De Maeseneer D, Reynders D, Goetghebeur E, Van Dorpe J, Verbeke S, Annala M, Brochez L, Van der Eecken K, Wyatt AW, Rottey S, Ost P. Randomized Phase 1 Trial of Pembrolizumab with Sequential Versus Concomitant Stereotactic Body Radiotherapy in Metastatic Urothelial Carcinoma. Eur Urol. 2019 May;75(5):707-711. doi: 10.1016/j.eururo.2019.01.009. Epub 2019 Jan 19.

    PubMed 30665814

  • Sundahl N, De Wolf K, Rottey S, Decaestecker K, De Maeseneer D, Meireson A, Goetghebeur E, Fonteyne V, Verbeke S, De Visschere P, Reynders D, Van Gele M, Brochez L, Ost P. A phase I/II trial of fixed-dose stereotactic body radiotherapy with sequential or concurrent pembrolizumab in metastatic urothelial carcinoma: evaluation of safety and clinical and immunologic response. J Transl Med. 2017 Jun 29;15(1):150. doi: 10.1186/s12967-017-1251-3.

    PubMed 28662677

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing pembrolizumab in people with Metastatic Urothelial Cancer, run by University Hospital, Ghent at 1 site in Belgium.

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 14 inclusion and 22 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: finished, as of the sponsor's last update on 17 Jul 2024. 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 Belgium. 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. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Selection of the sequence arm with a DLT < 20% based on the incidence of treatment-related adverse events (time frame: 12 weeks post-radiotherapy). 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 NCT02826564, which also lists 2 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 17 Jul 2024.

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