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Transitional Cell CarcinomaPhase 2PEBBLENCT04878250

Preoperative Bintrafusp Alfa in Operable Urothelial Carcinoma of the Bladder

A Phase 2 study testing Bintrafusp alfa in people with Transitional Cell Carcinoma and Bladder Cancer, run by Queen Mary University of London.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

PEBBLE is an open-label, international, multicentre, window of opportunity phase II trial that aims to evaluate the effects of short-term preoperative therapy with bintrafusp alfa in patients with histologically confirmed urothelial carcinoma requiring radical surgery with bilateral pelvic lymph node dissection. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Transitional Cell Carcinoma, Bladder Cancer
What is being tested?
Bintrafusp alfa
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
No sites listed yet
Study dates
Jun 2021to Jan 2025
Phase
Phase 2
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

  • Willing and able to provide written informed consent
  • Ability to comply with the protocol
  • Age ≥ 18 years
  • Histopathologically confirmed urothelial carcinoma (T2-T4aN0-1M0) of the bladder where radical cystectomy with bilateral pelvic lymph node dissection is indicated. Patients with "variant histology" such as micropapillary, plasmocytoid, nested, sarcomatoid, microcystic, squamous and adeno variants of urothelial carcinoma are required to have more than 50% of tumor tissue with transitional cell pattern.
  • Residual disease after TURBT or endoscopy (surgical opinion, cystoscopy or radiological presence).
  • Fit and planned for surgery (according to local guidelines).
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  • N0-1 and M0 disease CT or MRI (within 4 weeks of enrolment). Patients with N2 disease on cross sectional imaging are excluded from the study.
  • Representative formalin-fixed paraffin embedded (FFPE) tumour samples with an associated pathology report that are determined to be available and sufficient for central testing.
  • Patients who refuse neoadjuvant cisplatin-based chemotherapy or in whom neoadjuvant cisplatin-based therapy is not appropriate.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Negative serum pregnancy test within 14 days of Day 1 Cycle 1 for female patients of childbearing potential.
  • Highly effective method of contraception throughout the study until 2 months after the last dose of bintrafusp alfa for female patients of childbearing potential and 4 months after the last dose of bintrafusp alfa for male patients.
  • Adequate haematologic and end-organ function within 4 weeks prior to the first study treatment.

Who cannot join

  • Pregnant and lactating female patients.
  • Major surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
  • Previous intravenous chemotherapy or immune therapy for bladder cancer.
  • Patients with prior allogeneic stem cell or solid organ transplantation.
  • Prior treatment with CD137 agonists, anti-CTLA-4, anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents.
  • Has received any prior radiotherapy to the bladder.
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  • Patients must not have had oral or intravenous (IV) steroids for 14 days prior to Cycle 1 Day 1. The use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids (i.e., for adrenal insufficiency), and mineralocorticoids (e.g., fludrocortisone) is allowed at physiologic doses ≤ 10 mg/day of prednisone or equivalent.
  • Received therapeutic IV antibiotics within 14 days prior to enrolment (Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible).
  • Administration of a live, attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study. Seasonal flu vaccines that do not contain a live virus are permitted.
  • Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment.
  • Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to enrolment.
  • Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome).
  • Malignancies other than urothelial carcinoma of the bladder within 3 years prior to enrolment with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (Gleason score ≤ 3 + 4 and PSA < 10 ng/mL undergoing active surveillance and treatment naive).
  • Severe infections within 4 weeks prior to enrolment including but not limited to hospitalisation for complications of infection, bacteraemia, or severe pneumonia.
  • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 6 months prior to enrolment, unstable arrhythmias, or unstable angina.
  • History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organising pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan (History of radiation pneumonitis in the radiation field (fibrosis) is permitted).
  • Patients with uncontrolled Type 1 diabetes mellitus. Patients with Type 1 diabetes controlled on a stable insulin regimen are eligible.
  • Patients with active hepatitis infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
  • Positive test for HIV.
  • Patients with active tuberculosis.
  • History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. Patients with a history of autoimmune-related hypothyroidism, unless on a stable dose of thyroid-replacement hormone.
  • History of bleeding diathesis or recent major bleeding events (i.e. Grade ≥ 2 bleeding events in the 30 days prior to treatment
  • Has a diagnosis of immunodeficiency.
  • Receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.

Trial locations and contacts

No sites are listed yet.

PEBBLE Trial Coordinator contact

+44 (0) 2078828764

bci-pebble@qmul.ac.uk

About this study

Official title: A Phase II Study Investigating Preoperative Bintrafusp Alfa in Operable Urothelial Carcinoma of the Bladder

PEBBLE is an open-label, international, multicentre, window of opportunity phase II trial that aims to evaluate the effects of short-term preoperative therapy with bintrafusp alfa in patients with histologically confirmed urothelial carcinoma requiring radical surgery with bilateral pelvic lymph node dissection. Eligible patients will receive 4 doses of bintrafusp alfa (1200mg flat dose) at 14 day intervals before undergoing radical surgery. Patients will attend study visits at 6, 12 and 24 weeks following their surgery. After the 24-week post-surgical visit, patients will enter a follow up phase during which they will be contacted annually for 2 years after their surgery to collect survival and disease status data. The efficacy of bintrafusp alfa will be assessed on CT/MRI scan images and tumour tissue samples collected at baseline and after treatment with bintrafusp alfa.

Being tested
Bintrafusp alfa
Medical subject headings
Carcinoma, Transitional Cell, Urinary Bladder Neoplasms

What participants receive

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

  • Bintrafusp alfaDrug

    4 doses of bintrafusp alfa (1200mg flat dose) administered intravenously at 14 day intervals before undergoing radical cystectomy.

Study groups in NCT04878250
Study groupRoleWhat they receive
Bintrafusp alfaExperimentalNot described
Receives: Drug: Bintrafusp alfa

What is being measured

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

  1. Pathological complete response rate (pCRR)

    No microscopic evidence (pT0/Tis/Cis) of residual disease in the bladder based on histological evaluation of the resected bladder specimen collected during radical surgery

    Measured: Post - treatment with 4 cycles of bintrafusp alfa (1 cycle = 14 days)

Secondary outcomes (4)

  1. Dynamic changes in TGFb, T-effector signatures and CD8 count measured in tumour samples.

    Measured: Pre - and post - treatment with 4 cycles of bintrafusp alfa (1 cycle = 14 days)

  2. Incidence, nature and severity of adverse events (AE) graded according to NCI-CTCAE v5.0

    Measured: From time of consent until the safety visit, an average of 22 weeks.

  3. Disease free survival (DFS) defined as time between the date of enrolment to first evidence of relapse based on local investigator assessments or death, whichever occurs first.

    Measured: Up to 2 years

  4. Overall survival (OS) defined as the time between the date of enrolment and death due to any cause.

    Measured: Up to 2 years

Timeline

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

  1. First posted7 May 2021
  2. Study startJun 2021 (estimated)
  3. Primary completionJul 2023 (estimated)
  4. Study completionJan 2025 (estimated)

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
49 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04878250
Sponsor's protocol ID
PEBBLE
Acronym
PEBBLE
Status last verified
May 2021
First submitted
30 Apr 2021
Last updated
7 May 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bintrafusp alfa in people with Transitional Cell Carcinoma and Bladder Cancer, run by Queen Mary University of London.

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 13 inclusion and 24 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: status not confirmed, as of the sponsor's last update on 7 May 2021. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Results are not available in the source record.

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

Contact PEBBLE Trial Coordinator (+44 (0) 2078828764, bci-pebble@qmul.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological complete response rate (pCRR) (time frame: Post - treatment with 4 cycles of bintrafusp alfa (1 cycle = 14 days)). 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 NCT04878250.

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 7 May 2021.

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