Urothelial Bladder CarcinomaPhase 2PURE-01NCT02736266

Neoadjuvant Pembrolizumab for Muscle-invasive Urothelial Bladder Carcinoma

A Phase 2 study testing Pembrolizumab (MK-3475) in people with Urothelial Bladder Carcinoma, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.

Completed

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

Official record

Search all trials

Trial summary

Patients with T2-T4a N0 urothelial bladder carcinoma (UBC) with residual disease after transurethral resection of the bladder (TURB, surgical opinion, cystoscopy or radiological presence) will receive 3 cycles of pembrolizumab (MK-3475) at the dose of 200mg 3 weekly prior to surgery (radical cystectomy). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Urothelial Bladder Carcinoma
What is being tested?: Pembrolizumab (MK-3475)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 174 participants
Where: 1 siteItaly
Study dates: 27 Feb 2017to 23 Sep 2022
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 transitional cell carcinoma. Patients with mixed histologies are required to have a dominant (i.e. 50% at least) transitional cell pattern.
Fit and planned for cystectomy (according to local guidelines).
Clinical stage T2-T4a N0 M0 disease by CT (or MRI) + PET/CT (within 4 weeks of randomization by RECIST v1.1).

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Residual disease after TURB (surgical opinion, cystoscopy or radiological presence).
Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens (blocks preferred) or at least 15 unstained slides, with an associated pathology report, for testing at the study sponsor site and determined to be evaluable for tumor PD-L1 expression prior to study enrolment; patients with fewer than 15 unstained slides available at baseline (but no fewer than 10) may be eligible following discussion with Merck representatives.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
Adequate hematologic and end-organ function tests.

Who cannot join

Patients taking regular oral steroids, above the allowed limit of 10mg/day methylprednisolone or analogues, for any reason. Patients must not have had steroids for 28 days prior to study entry.
Previously intravenous chemotherapy bladder cancer. Patients who have previously had radiotherapy or concurrent chemo-radiation would be eligible.
Malignancies other than UBC within 5 years prior to Cycle 1, Day 1, 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).
Evidence of measurable nodal or metastatic disease.
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).
Pregnant female patients. All female patients of childbearing potential with a positive pregnancy test within 2 weeks prior to the first dose of study treatment will be excluded from the study.

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Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, unstable arrhythmias, or unstable angina.
Severe infections within 4 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
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.
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the pembrolizumab formulation
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 a history of autoimmune-related hypothyroidism, unless on a stable dose of thyroid-replacement hormone.
Patients with uncontrolled Type 1 diabetes mellitus
Uncontrolled hypercalcemia
Patients with prior allogeneic stem cell or solid organ transplantation.
History of idiopathic pulmonary fibrosis
Positive test for HIV.
Patients with active hepatitis infection
Patients with active tuberculosis.
Prior treatment with anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents.
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
Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrolment
History of severe immune-related adverse effects from anti-CTLA-4 (CTCAE Grade 3 and 4).
Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment.

Trial locations and contacts

1 site in 1 country.

Italy1 site

Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Mi, 20133

Other trials in Italy

About this study

Official title: An Open Label, Single-arm, Phase 2 Study of Neoadjuvant Pembrolizumab (MK-3475) Before Cystectomy for Patients With Muscle-invasive Urothelial Bladder Cancer.

Computed tomography (CT) scan and fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan will be done during screening and before surgery. After cystectomy, patients with the evidence of pathologic stage T3-4 (pT3-4) and/or pathologically node-positive disease will be managed according to local guidelines. Further anti programmed-death (PD)-1 or anti PD-ligand 1 (PD-L1) therapy will not be given post-operatively.

PD-L1 status will be centralized and assessed on TURB specimen using an anti-PD-L1 antibody (Ab) and a prototype immunohistochemical (IHC) assay. PD-L1 positivity will be defined as any staining in the stroma or in ≥1% of tumor cells.

Pathologic complete response (pCR) is the primary endpoint. All patients enrolled who receive at least 1 cycle of study drug will be includes in the intention-to-treat (ITT) analysis.

The alternative hypothesis (H1) is pCR ≥20% and null hypothesis (H0) pCR≤10%. A 2-stage design will be used to estimate the number of pts required. Out of 90 pts overall, with the first stage of 49 pts, ≥6 pCR will be required in the first stage, and ≥13 pCR in the whole study population (80% power and a 2-sided test of significance at the 10% level).

Correlative research on tissue/blood samples will include immune-cell profiling in tumor and blood during Pembrolizumab, cytokine assessment, and molecular profiling of tumor samples.

Read the detailed description

Conditions: Urothelial Bladder Carcinoma
Being tested: Pembrolizumab (MK-3475)
Keywords: Muscle-invasive, Urothelial bladder carcinoma, Neoadjuvant therapy, Radical cystectomy

What participants receive

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

Pembrolizumab (MK-3475)Drug
Also called Keytruda
Pembrolizumab given intravenously in 30 min. infusion every 3 weeks

Study groups in NCT02736266
Study group	Role	What they receive
Pembrolizumab (MK-3475)	Experimental	Pembrolizumab (MK-3475) will be administered at the dose of 200mg, as a 30-minute intravenous infusion, every 3 weeks, for a total of 3 cycles prior to radical cystectomy. Receives: Drug: Pembrolizumab (MK-3475)

What is being measured

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

Pathologic complete response
Absence of residual viable tumor in the radical cystectomy specimen
Measured: At the time of radical cystectomy (within 9 weeks of the first dose of pembrolizumab)

Secondary outcomes (3)

Adverse events
Number of patients developing side effects
Measured: Up to 2 years
Percentage of treatment-related delay in surgery
Number of patients undergoing cystectomy later than 12 weeks after pembrolizumab treatment
Measured: Starting at week 9
Frequency of treatment-related adverse events
Number of patients developing side effects
Measured: Up to 1 year

Timeline

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

27 Feb 201723 Sep 2022

First posted13 Apr 2016 (estimated)
Study start27 Feb 2017
Primary completion20 Oct 2018
Study completion23 Sep 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (20)Papers the sponsor has linked to this study.
Other trials for Urothelial Bladder CarcinomaStudies of the same condition, open and under way.
More trials run by Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: 174 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02736266
Sponsor's protocol ID: INT 101/16
Other IDs: 2015-002055-10, 2015
Acronym: PURE-01
Status last verified: Nov 2022
First submitted: 9 Apr 2016
Last updated: 18 Jul 2023
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: No formal plan

Publications

Brembilla G, Basile G, Cosenza M, Giganti F, Del Prete A, Russo T, Pennella R, Lavalle S, Raggi D, Mercinelli C, Tateo V, Cigliola A, Patane D, Crupi E, Giannatempo P, Messina A, Calareso G, Martini A, Bandini M, Moschini M, Cardone G, Briganti A, Montorsi F, Necchi A, De Cobelli F. Neoadjuvant Chemotherapy VI-RADS Scores for Assessing Muscle-invasive Bladder Cancer Response to Neoadjuvant Immunotherapy with Multiparametric MRI. Radiology. 2024 Dec;313(3):e233020. doi: 10.1148/radiol.233020.
PubMed 39718497
Reike MJ, Raggi D, Mercinelli C, Cigliola A, Tateo V, Patane DA, Crupi E, de Padua TC, Black PC, Gibb EA, Necchi A. Distinct Gene Expression Patterns Identify Patients who Relapse After Neoadjuvant Pembrolizumab and Radical Cystectomy in the PURE-01 Study. Clin Genitourin Cancer. 2024 Dec;22(6):102214. doi: 10.1016/j.clgc.2024.102214. Epub 2024 Sep 20.
PubMed 39455338
Li R, Nocera L, Rose KM, Raggi D, Naidu S, Mercinelli C, Cigliola A, Tateo V, Patane D, Grass GD, Gilbert SM, Sexton WJ, Bandini M, Moschini M, Briganti A, Montorsi F, Spiess PE, Necchi A. Comparative Effectiveness of Neoadjuvant Pembrolizumab Versus Cisplatin-based Chemotherapy or Upfront Radical Cystectomy in Patients with Muscle-invasive Urothelial Bladder Cancer. Eur Urol Oncol. 2024 Jun;7(3):614-624. doi: 10.1016/j.euo.2023.12.008. Epub 2024 Jan 6.
PubMed 38184473
Necchi A, Basile G, Gibb EA, Raggi D, Calareso G, de Padua TC, Patane D, Crupi E, Mercinelli C, Cigliola A, Tateo V, Giannatempo P, Moschini M, Briganti A, Montorsi F, Messina A, Ross JS, Pavlick D, De Cobelli F, Brembilla G. Vesical Imaging-Reporting and Data System use predicting the outcome of neoadjuvant pembrolizumab in muscle-invasive bladder cancer. BJU Int. 2024 Feb;133(2):214-222. doi: 10.1111/bju.16191. Epub 2023 Oct 16.
PubMed 37803523
Basile G, Bandini M, Gibb EA, Ross JS, Raggi D, Marandino L, Costa de Padua T, Crupi E, Colombo R, Colecchia M, Luciano R, Nocera L, Moschini M, Briganti A, Montorsi F, Necchi A. Neoadjuvant Pembrolizumab and Radical Cystectomy in Patients with Muscle-Invasive Urothelial Bladder Cancer: 3-Year Median Follow-Up Update of PURE-01 Trial. Clin Cancer Res. 2022 Dec 1;28(23):5107-5114. doi: 10.1158/1078-0432.CCR-22-2158.
PubMed 36190522
Martini A, Raggi D, Marandino L, Montorsi F, Ross JS, Gibb EA, Necchi A. The Paradoxical Role of Body Mass Index in Patients with Muscle-invasive Bladder Cancer Receiving Neoadjuvant Immunotherapy. Eur Urol Oncol. 2022 Jun;5(3):370-372. doi: 10.1016/j.euo.2022.02.004. Epub 2022 Mar 10. No abstract available.
PubMed 35283158
Necchi A, Martini A, Raggi D, Cucchiara V, Colecchia M, Luciano R, Villa L, Mazzone E, Basile G, Scuderi S, Pederzoli F, Bandini M, Barletta F, Larcher A, Capitanio U, Salonia A, Briganti A, Ross JS, Messina A, Montorsi F. A feasibility study of preoperative pembrolizumab before radical nephroureterectomy in patients with high-risk, upper tract urothelial carcinoma: PURE-02. Urol Oncol. 2022 Jan;40(1):10.e1-10.e6. doi: 10.1016/j.urolonc.2021.05.014. Epub 2021 Jun 17.
PubMed 34147313
Trevisani F, Di Marco F, Raggi D, Bettiga A, Vago R, Larcher A, Cinque A, Salonia A, Briganti A, Capitanio U, Necchi A, Montorsi F. Renal function outcomes in patients with muscle-invasive bladder cancer treated with neoadjuvant pembrolizumab and radical cystectomy in the PURE-01 study. Int J Cancer. 2021 Jul 1;149(1):186-190. doi: 10.1002/ijc.33554. Epub 2021 Mar 26.
PubMed 33720424
Marandino L, Capozza A, Bandini M, Raggi D, Fare E, Pederzoli F, Gallina A, Capitanio U, Bianchi M, Gandaglia G, Fossati N, Colecchia M, Giannatempo P, Serafini G, Padovano B, Salonia A, Briganti A, Montorsi F, Alessi A, Necchi A. Incidence and Clinical Impact of Inflammatory Fluorodeoxyglucose Positron Emission Tomography Uptake After Neoadjuvant Pembrolizumab in Patients with Organ-confined Bladder Cancer Undergoing Radical Cystectomy. Eur Urol Focus. 2021 Sep;7(5):1092-1099. doi: 10.1016/j.euf.2020.10.003. Epub 2020 Nov 7.
PubMed 33172772
Marandino L, Capozza A, Bandini M, Raggi D, Fare E, Pederzoli F, Gallina A, Capitanio U, Bianchi M, Gandaglia G, Fossati N, Colecchia M, Giannatempo P, Serafini G, Padovano B, Salonia A, Briganti A, Montorsi F, Alessi A, Necchi A. [18F]Fluoro-Deoxy-Glucose positron emission tomography to evaluate lymph node involvement in patients with muscle-invasive bladder cancer receiving neoadjuvant pembrolizumab. Urol Oncol. 2021 Apr;39(4):235.e15-235.e21. doi: 10.1016/j.urolonc.2020.09.035. Epub 2020 Oct 16.
PubMed 33071107
Bandini M, Gibb EA, Gallina A, Raggi D, Marandino L, Bianchi M, Ross JS, Colecchia M, Gandaglia G, Fossati N, Pederzoli F, Luciano R, Colombo R, Salonia A, Briganti A, Montorsi F, Necchi A. Does the administration of preoperative pembrolizumab lead to sustained remission post-cystectomy? First survival outcomes from the PURE-01 study☆. Ann Oncol. 2020 Dec;31(12):1755-1763. doi: 10.1016/j.annonc.2020.09.011. Epub 2020 Sep 23.
PubMed 32979511
Pederzoli F, Bandini M, Marandino L, Raggi D, Giannatempo P, Salonia A, Gallina A, Briganti A, Montorsi F, Necchi A. Neoadjuvant Chemotherapy or Immunotherapy for Clinical T2N0 Muscle-invasive Bladder Cancer: Time to Change the Paradigm? Eur Urol Oncol. 2021 Dec;4(6):1006-1010. doi: 10.1016/j.euo.2020.07.006. Epub 2020 Aug 23.
PubMed 32847746
Bandini M, Calareso G, Raggi D, Marandino L, Colecchia M, Gallina A, Giannatempo P, Pederzoli F, Gandaglia G, Fossati N, Capitanio U, Colombo R, Salonia A, Briganti A, Montorsi F, De Cobelli F, Messina A, Necchi A. The Value of Multiparametric Magnetic Resonance Imaging Sequences to Assist in the Decision Making of Muscle-invasive Bladder Cancer. Eur Urol Oncol. 2021 Oct;4(5):829-833. doi: 10.1016/j.euo.2020.06.004. Epub 2020 Jun 27.
PubMed 32605888
Bandini M, Ross JS, Raggi D, Gallina A, Colecchia M, Luciano R, Giannatempo P, Fare E, Pederzoli F, Bianchi M, Colombo R, Gandaglia G, Fossati N, Marandino L, Capitanio U, Deho' F, Ali SM, Madison R, Chung JH, Salonia A, Briganti A, Montorsi F, Necchi A. Predicting the Pathologic Complete Response After Neoadjuvant Pembrolizumab in Muscle-Invasive Bladder Cancer. J Natl Cancer Inst. 2021 Jan 4;113(1):48-53. doi: 10.1093/jnci/djaa076.
PubMed 32516377
Necchi A, Raggi D, Giannatempo P, Marandino L, Fare E, Gallina A, Colecchia M, Luciano R, Salonia A, Gandaglia G, Fossati N, Bandini M, Pederzoli F, Dittamore R, Liu Y, Davicioni E, Ross JS, de Jong JJ, Briganti A, Montorsi F, Gibb EA. Can Patients with Muscle-invasive Bladder Cancer and Fibroblast Growth Factor Receptor-3 Alterations Still Be Considered for Neoadjuvant Pembrolizumab? A Comprehensive Assessment from the Updated Results of the PURE-01 Study. Eur Urol Oncol. 2021 Dec;4(6):1001-1005. doi: 10.1016/j.euo.2020.04.005. Epub 2020 May 14.
PubMed 32417369

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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RecruitingPhase 2
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
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FORAGER-1: A Study of Vepugratinib (LY3866288; LOXO-435) in Participants With Cancer With a Change in a Gene Called FGFR3
Urinary Bladder Neoplasms, Neoplasm Metastasis

All Urothelial Bladder Carcinoma trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open Label, Single-arm, Phase 2 Study of Neoadjuvant Pembrolizumab (MK-3475) Before Cystectomy for Patients With Muscle-invasive Urothelial Bladder Cancer.
ClinicalTrials.gov ID: NCT02736266
Acronym / sponsor ID: PURE-01 / INT 101/16
Conditions: Urothelial Bladder Carcinoma
Keywords: Muscle-invasive, Urothelial bladder carcinoma, Neoadjuvant therapy, Radical cystectomy
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 174 participants (actual)
Lead sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoUniversity, hospital or other
Collaborators: Merck Sharp & Dohme LLC
Study start: 27 Feb 2017 (actual)
Primary completion: 20 Oct 2018 (actual)
Study completion: 23 Sep 2022 (actual)
First posted: 13 Apr 2016 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Pathologic complete response (pCR) is the primary endpoint. All patients enrolled who receive at least 1 cycle of study drug will be includes in the intention-to-treat (ITT) analysis.

Correlative research on tissue/blood samples will include immune-cell profiling in tumor and blood during Pembrolizumab, cytokine assessment, and molecular profiling of tumor samples.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Pembrolizumab (MK-3475)	Experimental	Drug: Pembrolizumab (MK-3475)Pembrolizumab (MK-3475) will be administered at the dose of 200mg, as a 30-minute intravenous infusion, every 3 weeks, for a total of 3 cycles prior to radical cystectomy.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Willing and able to provide written informed consent.
Ability to comply with the protocol.
Age ≥ 18 years.
Histopathologically confirmed transitional cell carcinoma. Patients with mixed histologies are required to have a dominant (i.e. 50% at least) transitional cell pattern.
Fit and planned for cystectomy (according to local guidelines).

Key exclusion criteria (25 listed)

Patients taking regular oral steroids, above the allowed limit of 10mg/day methylprednisolone or analogues, for any reason. Patients must not have had steroids for 28 days prior to study entry.
Previously intravenous chemotherapy bladder cancer. Patients who have previously had radiotherapy or concurrent chemo-radiation would be eligible.
Malignancies other than UBC within 5 years prior to Cycle 1, Day 1, 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).
Evidence of measurable nodal or metastatic disease.
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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Pembrolizumab (MK-3475)Also: KeytrudaPembrolizumab given intravenously in 30 min. infusion every 3 weeks	Drug	Pembrolizumab (MK-3475)

Primary outcome

Pathologic complete response
Time frame: At the time of radical cystectomy (within 9 weeks of the first dose of pembrolizumab)
Absence of residual viable tumor in the radical cystectomy specimen

3 secondary outcomes

Adverse events
Time frame: Up to 2 years
Percentage of treatment-related delay in surgery
Time frame: Starting at week 9
Frequency of treatment-related adverse events
Time frame: Up to 1 year

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2023.
Derived from this study: PubMed 39718497Brembilla G, Basile G, Cosenza M, Giganti F, Del Prete A, Russo T, Pennella R, Lavalle S, Raggi D, Mercinelli C, Tateo V, Cigliola A, Patane D, Crupi E, Giannatempo P, Messina A, Calareso G, Martini A, Bandini M, Moschini M, Cardone G, Briganti A, Montorsi F, Necchi A, De Cobelli F. Neoadjuvant Chemotherapy VI-RADS Scores for Assessing Muscle-invasive Bladder Cancer Response to Neoadjuvant Immunotherapy with Multiparametric MRI. Radiology. 2024 Dec;313(3):e233020. doi: 10.1148/radiol.233020.
Derived from this study: PubMed 39455338Reike MJ, Raggi D, Mercinelli C, Cigliola A, Tateo V, Patane DA, Crupi E, de Padua TC, Black PC, Gibb EA, Necchi A. Distinct Gene Expression Patterns Identify Patients who Relapse After Neoadjuvant Pembrolizumab and Radical Cystectomy in the PURE-01 Study. Clin Genitourin Cancer. 2024 Dec;22(6):102214. doi: 10.1016/j.clgc.2024.102214. Epub 2024 Sep 20.
Derived from this study: PubMed 38184473Li R, Nocera L, Rose KM, Raggi D, Naidu S, Mercinelli C, Cigliola A, Tateo V, Patane D, Grass GD, Gilbert SM, Sexton WJ, Bandini M, Moschini M, Briganti A, Montorsi F, Spiess PE, Necchi A. Comparative Effectiveness of Neoadjuvant Pembrolizumab Versus Cisplatin-based Chemotherapy or Upfront Radical Cystectomy in Patients with Muscle-invasive Urothelial Bladder Cancer. Eur Urol Oncol. 2024 Jun;7(3):614-624. doi: 10.1016/j.euo.2023.12.008. Epub 2024 Jan 6.
Derived from this study: PubMed 37803523Necchi A, Basile G, Gibb EA, Raggi D, Calareso G, de Padua TC, Patane D, Crupi E, Mercinelli C, Cigliola A, Tateo V, Giannatempo P, Moschini M, Briganti A, Montorsi F, Messina A, Ross JS, Pavlick D, De Cobelli F, Brembilla G. Vesical Imaging-Reporting and Data System use predicting the outcome of neoadjuvant pembrolizumab in muscle-invasive bladder cancer. BJU Int. 2024 Feb;133(2):214-222. doi: 10.1111/bju.16191. Epub 2023 Oct 16.
Derived from this study: PubMed 36190522Basile G, Bandini M, Gibb EA, Ross JS, Raggi D, Marandino L, Costa de Padua T, Crupi E, Colombo R, Colecchia M, Luciano R, Nocera L, Moschini M, Briganti A, Montorsi F, Necchi A. Neoadjuvant Pembrolizumab and Radical Cystectomy in Patients with Muscle-Invasive Urothelial Bladder Cancer: 3-Year Median Follow-Up Update of PURE-01 Trial. Clin Cancer Res. 2022 Dec 1;28(23):5107-5114. doi: 10.1158/1078-0432.CCR-22-2158.
Derived from this study: PubMed 35283158Martini A, Raggi D, Marandino L, Montorsi F, Ross JS, Gibb EA, Necchi A. The Paradoxical Role of Body Mass Index in Patients with Muscle-invasive Bladder Cancer Receiving Neoadjuvant Immunotherapy. Eur Urol Oncol. 2022 Jun;5(3):370-372. doi: 10.1016/j.euo.2022.02.004. Epub 2022 Mar 10. No abstract available.
Derived from this study: PubMed 34147313Necchi A, Martini A, Raggi D, Cucchiara V, Colecchia M, Luciano R, Villa L, Mazzone E, Basile G, Scuderi S, Pederzoli F, Bandini M, Barletta F, Larcher A, Capitanio U, Salonia A, Briganti A, Ross JS, Messina A, Montorsi F. A feasibility study of preoperative pembrolizumab before radical nephroureterectomy in patients with high-risk, upper tract urothelial carcinoma: PURE-02. Urol Oncol. 2022 Jan;40(1):10.e1-10.e6. doi: 10.1016/j.urolonc.2021.05.014. Epub 2021 Jun 17.
Derived from this study: PubMed 33720424Trevisani F, Di Marco F, Raggi D, Bettiga A, Vago R, Larcher A, Cinque A, Salonia A, Briganti A, Capitanio U, Necchi A, Montorsi F. Renal function outcomes in patients with muscle-invasive bladder cancer treated with neoadjuvant pembrolizumab and radical cystectomy in the PURE-01 study. Int J Cancer. 2021 Jul 1;149(1):186-190. doi: 10.1002/ijc.33554. Epub 2021 Mar 26.
Derived from this study: PubMed 33172772Marandino L, Capozza A, Bandini M, Raggi D, Fare E, Pederzoli F, Gallina A, Capitanio U, Bianchi M, Gandaglia G, Fossati N, Colecchia M, Giannatempo P, Serafini G, Padovano B, Salonia A, Briganti A, Montorsi F, Alessi A, Necchi A. Incidence and Clinical Impact of Inflammatory Fluorodeoxyglucose Positron Emission Tomography Uptake After Neoadjuvant Pembrolizumab in Patients with Organ-confined Bladder Cancer Undergoing Radical Cystectomy. Eur Urol Focus. 2021 Sep;7(5):1092-1099. doi: 10.1016/j.euf.2020.10.003. Epub 2020 Nov 7.
Derived from this study: PubMed 33071107Marandino L, Capozza A, Bandini M, Raggi D, Fare E, Pederzoli F, Gallina A, Capitanio U, Bianchi M, Gandaglia G, Fossati N, Colecchia M, Giannatempo P, Serafini G, Padovano B, Salonia A, Briganti A, Montorsi F, Alessi A, Necchi A. [18F]Fluoro-Deoxy-Glucose positron emission tomography to evaluate lymph node involvement in patients with muscle-invasive bladder cancer receiving neoadjuvant pembrolizumab. Urol Oncol. 2021 Apr;39(4):235.e15-235.e21. doi: 10.1016/j.urolonc.2020.09.035. Epub 2020 Oct 16.
Derived from this study: PubMed 32979511Bandini M, Gibb EA, Gallina A, Raggi D, Marandino L, Bianchi M, Ross JS, Colecchia M, Gandaglia G, Fossati N, Pederzoli F, Luciano R, Colombo R, Salonia A, Briganti A, Montorsi F, Necchi A. Does the administration of preoperative pembrolizumab lead to sustained remission post-cystectomy? First survival outcomes from the PURE-01 study☆. Ann Oncol. 2020 Dec;31(12):1755-1763. doi: 10.1016/j.annonc.2020.09.011. Epub 2020 Sep 23.
Derived from this study: PubMed 32847746Pederzoli F, Bandini M, Marandino L, Raggi D, Giannatempo P, Salonia A, Gallina A, Briganti A, Montorsi F, Necchi A. Neoadjuvant Chemotherapy or Immunotherapy for Clinical T2N0 Muscle-invasive Bladder Cancer: Time to Change the Paradigm? Eur Urol Oncol. 2021 Dec;4(6):1006-1010. doi: 10.1016/j.euo.2020.07.006. Epub 2020 Aug 23.
Individual participant dataSharing planned: No. No formal plan

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Filippo G. de Braud, MD principal investigator

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab (MK-3475) in people with Urothelial Bladder Carcinoma, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.

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 10 inclusion and 25 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 18 Jul 2023. 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 Italy. 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 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?

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?

Pathologic complete response (time frame: At the time of radical cystectomy (within 9 weeks of the first dose of pembrolizumab)). 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 NCT02736266, which also lists 20 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 18 Jul 2023; AzTrials last refreshed its copy on 8 Nov 2026.