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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 12 December 2020
Main ID:  NCT02256436
Date of registration: 29/09/2014
Prospective Registration: Yes
Primary sponsor: Merck Sharp & Dohme Corp.
Public title: A Study of Pembrolizumab (MK-3475) Versus Paclitaxel, Docetaxel, or Vinflunine for Participants With Advanced Urothelial Cancer (MK-3475-045/KEYNOTE-045)
Scientific title: A Phase III Randomized Clinical Trial of Pembrolizumab (MK-3475) Versus Paclitaxel, Docetaxel or Vinflunine in Subjects With Recurrent or Progressive Metastatic Urothelial Cancer
Date of first enrolment: October 22, 2014
Target sample size: 542
Recruitment status: Completed
URL:  https://clinicaltrials.gov/show/NCT02256436
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 3
Countries of recruitment
Australia Austria Belgium Canada Chile Denmark France Germany
Hungary Ireland Israel Italy Japan Korea, Republic of Netherlands New Zealand
Norway Peru Poland Portugal Puerto Rico Romania Singapore Spain
Sweden Taiwan Turkey United Kingdom United States
Contacts
Name:     Medical Director
Address: 
Telephone:
Email:
Affiliation:  Merck Sharpe & Dohme Corp.
Key inclusion & exclusion criteria

Inclusion criteria:

- Histologically- or cytologically-confirmed diagnosis of urothelial cancer of the renal
pelvis, ureter, bladder, or urethra, that is transitional cell or mixed
transitional/non-transitional (predominantly transitional) cell type

- Progression or recurrence of urothelial cancer following a first-line
platinum-containing regimen (e.g cisplatin, carboplatin) for metastatic or inoperable
locally advanced disease; or adjuvant platinum-based therapy following cystectomy for
localized muscle-invasive urothelial cancer with recurrence/progression <=12 months
following completion of therapy; or neoadjuvant platinum-containing therapy prior to
cystectomy for localized muscle-invasive urothelial cancer with recurrence <=12 months
following completion of therapy

- No more than 2 prior lines of systemic chemotherapy for metastatic urothelial cancer

- Able to provide tissue for biomarker analysis from an archival tissue sample or newly
obtained core or excisional biopsy of a tumor lesion not previously irradiated

- Measureable disease

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

- Adequate organ function

- Female participants of childbearing potential have a negative urine or serum pregnancy
test; or are surgically sterile, or willing to use 2 acceptable methods of birth
control, or abstain from heterosexual activity for the course of the study through 120
days after the last dose of pembrolizumab or 180 days after the last dose of
paclitaxel, docetaxel, or vinflunine

- Male participants must be willing to use an adequate method of contraception starting
with the first dose of study medication through 120 days after the last dose of
pembrolizumab or 180 days after the last dose of paclitaxel, docetaxel, or vinflunine

Exclusion criteria:

- Urothelial cancer that is suitable for local therapy administered with curative intent

- Currently participating in or has participated in a study of an investigational agent
or using an investigational device within 4 weeks prior to the first dose of trial
medication

- Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form
of immunosuppressive therapy within 7 days prior to the first dose of study medication

- Anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not
recovered from adverse events due to agents administered more than 4 weeks earlier

- Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2
weeks of study Day 1 or not recovered from adverse events due to a previously
administered agent

- Prior therapy with all choices of active comparator

- Known additional malignancy that is progressing or requires active treatment with the
exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin
that has undergone potentially curative therapy or in situ cancer; or prostate cancer
that was identified incidentally following cystoprostatectomy for bladder cancer that
is Stage T2N0M0 or lower, Gleason score<= 6, or prostatic-specific antigen (PSA)
undetectable

- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis

- Active autoimmune disease requiring systemic treatment within the past 3 months or a
documented history of clinically severe autoimmune disease, or a syndrome that
requires systemic or immunosuppressive agents

- Active cardiac disease

- Evidence of interstitial lung disease or active non-infectious pneumonitis

- Active infection requiring systemic therapy

- History of severe hypersensitivity reaction to paclitaxel, docetaxel, or to other
drugs formulated with polysorbate 80 or polyoxyethylated castor oil, or to vinflunine
or other vinca alkaloids

- Requires ongoing therapy with a medication that is a strong inhibitor or inducer of
the cytochrome 3A4 (CYP3A4) enzymes

- Pregnant, breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 120 days
after the last dose of pembrolizumab or 180 days after the last dose of paclitaxel,
docetaxel, or vinflunine

- Prior therapy with an anti-programmed cell death 1 (PD-1) or anti-PD-Ligand 1 agent,
or with an agent directed to another co-inhibitory T-cell receptor

- Human immunodeficiency virus (HIV)

- Active hepatitis B or hepatitis C

- Received a live virus vaccine within 30 days of planned start of trial treatment



Age minimum: 18 Years
Age maximum: N/A
Gender: All
Health Condition(s) or Problem(s) studied
Urothelial Cancer
Intervention(s)
Drug: docetaxel
Drug: paclitaxel
Biological: pembrolizumab
Drug: vinflunine
Primary Outcome(s)
PFS Per RECIST 1.1 - Participants With PD-L1 Positive Tumors [Time Frame: Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)]
Overall Survival (OS) - All Participants [Time Frame: Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)]
OS - Participants With PD-L1 Positive Tumors [Time Frame: Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)]
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - All Participants [Time Frame: Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)]
OS - Participants With Strongly PD-L1 Positive Tumors [Time Frame: Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)]
PFS Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors [Time Frame: Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)]
Secondary Outcome(s)
ORR Per Modified RECIST - All Participants [Time Frame: Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)]
PFS Per Modified RECIST - All Participants [Time Frame: Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)]
Objective Response Rate (ORR) Per RECIST 1.1 - All Participants [Time Frame: Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)]
ORR Per RECIST 1.1 - Participants With PD-L1 Positive Tumors [Time Frame: Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)]
Number of Participants Who Discontinued Study Treatment Due to an AE [Time Frame: Up to approximately 20 months]
ORR Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors [Time Frame: Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)]
Number of Participants Who Experienced an Adverse Event (AE) [Time Frame: Up to approximately 23 months]
Response Duration Per RECIST 1.1 - All Participants [Time Frame: Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)]
Response Duration Per RECIST 1.1 - Participants With PD-L1 Positive Tumors [Time Frame: Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)]
Response Duration Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors [Time Frame: Through database cutoff date of 07-Sep-2016 (Up to approximately 20 months)]
Secondary ID(s)
2014-002009-40
MK-3475-045
152903
3475-045
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results
Results available: Yes
Date Posted: 31/08/2017
Date Completed:
URL: https://clinicaltrials.gov/ct2/show/results/NCT02256436
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