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BRIEF TITLE: Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Participants With Muscle-invasive Bladder Cancer (MIBC) (KEYNOTE-992)

A Phase 3, Randomized, Double-blind, Placebo-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Participants With Muscle-invasive Bladder Cancer (MIBC) (KEYNOTE-992)


  • Org Study ID: 3475-992
  • Secondary ID: MK-3475-992,2019-004023-20
  • NCT ID: NCT04241185
  • NCT Alias:
  • Sponsor: Merck Sharp & Dohme Corp. - Industry
  • Source: Merck Sharp & Dohme Corp.

Brief Summary

This study is designed to assess the antitumor efficacy and safety of pembrolizumab in combination with chemoradiotherapy (CRT) versus CRT alone in participants with muscle-invasive bladder cancer (MIBC). The primary hypothesis is that pembrolizumab + chemoradiotherapy is superior to placebo + chemoradiotherapy with respect to bladder intact event-free survival.

Overal Status Start Date Phase Study Type
Recruiting May 19, 2020 Phase 3 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Bladder Intact Event-Free Survival (BI-EFS)

Primary Outcome 1 - Time Frame: Up to approximately 71 months

Condition:

  • Urinary Bladder Neoplasms

Eligibility

Criteria:
Inclusion Criteria:

- Has a histologically confirmed diagnosis of MIBC with predominant urothelial histology

- Has clinically non-metastatic bladder cancer (N0M0)

- Has planned and is eligible to receive chemoradiotherapy (CRT) and one of the
protocol-specified radiosensitizing chemotherapy regimens

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

- Demonstrates adequate organ function

- Male participants are eligible to participate if they agree to the following during
the intervention period and for at least 180 days after the last dose of study
intervention:

- Refrain from donating sperm

- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle
(abstinent on a long term and persistent basis) and agree to remain abstinent; or
must agree to use contraception unless confirmed to be azoospermic

- A female participant is eligible to participate if she is not pregnant or
breastfeeding, and at least one of the following conditions applies:

- Is not a woman of childbearing potential (WOCBP)

- Is a WOCBP and using a contraceptive method that is highly effective (with a
failure rate of <1% per year), with low user dependency or be abstinent from
heterosexual intercourse as their preferred and usual lifestyle (abstinent on a
long term and persistent basis), during the intervention period and for at least
180 days after the last dose of study intervention; and agrees not to donate eggs
(ova, oocytes) to others or freeze/store for her own use for the purpose of
reproduction during this period

Exclusion Criteria:

- Has the presence of diffuse carcinoma in situ (CIS) (multiple foci of CIS) throughout
the bladder

- Has the presence of urothelial carcinoma (UC) at any site outside of the urinary
bladder in the previous 2 years except for Ta stage/T1 stage/CIS of the upper tract if
the participant has undergone a complete nephroureterectomy

- Has a known additional malignancy that is progressing or has required active therapy
within the past 3 years, except basal cell carcinoma of the skin, squamous cell
carcinoma of the skin, superficial bladder cancer or other carcinoma in situ that has
undergone potentially curative therapy

- Has the presence of bilateral hydronephrosis

- Has limited bladder function with frequency of small amounts of urine (< 30 mL),
urinary incontinence, or requires self-catheterization or a permanent indwelling
catheter

- Has received prior pelvic/local radiation therapy or any antineoplastic treatment for
muscle-invasive bladder cancer (MIBC). Treatment for non-muscle invasive bladder
cancer (NMIBC) with intravesical instillation therapy that was completed ≥28 days
prior to randomization is allowed. Prior systemic treatment of NMIBC is not permitted.

- Received prior therapy with an anti-PD-1 (programmed cell death protein 1), anti-PD-L1
(programmed death-ligand 1), or anti-PD-L2 (programmed cell death 1 ligand 2), or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,
CTLA-4 [cytotoxic T-lymphocyte-associated protein 4], OX 40, or CD137 [cluster of
differentiation 137])

- Has received a live vaccine within 30 days prior to the first dose of study drug

- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose of
study intervention

- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or the selected
chemotherapy regimen, and/or any of their excipients

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing 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

- Has an active autoimmune disease that has required systemic treatment in the past 2
years (ie, 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) is not considered a form
of systemic treatment and is allowed

- Has a history of non-infectious pneumonitis that required steroids or has current
pneumonitis

- Has an active infection requiring systemic therapy

- Has a known history of human immunodeficiency virus (HIV) infection

- Has a known history of Hepatitis B or known active Hepatitis C virus infection

- Has a known history of active tuberculosis (TB; Bacillus tuberculosis)

- Has a known psychiatric or substance abuse disorder that would interfere with the
participant's ability to cooperate with the requirements of the study

- Has had an allogenic tissue/solid organ transplant
Show More

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Medical Director

Role: Study Director

Affiliation: Merck Sharp & Dohme Corp.

Overall Contact

Name: Toll Free Number

Phone: 1-888-577-8839

Email: Trialsites@merck.com

Locations

Facility Status Contact
Carolina Urologic Research Center ( Site 0002)
Myrtle Beach, South Carolina 29572
United States
Recruiting Study Coordinator
843-449-1010 ext. 257
Fakultni nemocnice Olomouc ( Site 0559)
Olomouc, 779 00
Czechia
Recruiting Study Coordinator
+420588444295
2. LF UK a FN Motol ( Site 0555)
Praha 5, 150 06
Czechia
Recruiting Study Coordinator
+420266084516
Herlev og Gentofte Hospital. ( Site 0401)
Herlev, Hovedstaden 2730
Denmark
Recruiting Study Coordinator
4538689572
Odense Universitetshospital ( Site 0403)
Odense, Syddanmark 5000
Denmark
Recruiting Study Coordinator
4538689572
Tartu University Hospital ( Site 0079)
Tartu, Tartumaa 51014
Estonia
Recruiting Study Coordinator
+3727318815
Rambam Medical Center ( Site 0088)
Afula, HaTsafon 1834111
Israel
Recruiting Study Coordinator
+97247773811
Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0192)
Napoli, 80131
Italy
Recruiting Study Coordinator
+390815903637
National Cancer Center ( Site 0202)
Gyeonggi-do, Kyonggi-do 10408
Korea, Republic of
Recruiting Study Coordinator
+82319203679
Seoul National University Bundang Hospital ( Site 0204)
Seongnam-si, Kyonggi-do 13620
Korea, Republic of
Recruiting Study Coordinator
+82317877071
Korea University Anam Hospital ( Site 0205)
Seoul, Seoul-teukbyeolsi [Seoul] 02841
Korea, Republic of
Recruiting Study Coordinator
+8229206267
Severance Hospital Yonsei University Health System ( Site 0201)
Seoul, Seoul-teukbyeolsi [Seoul] 03722
Korea, Republic of
Recruiting Study Coordinator
+82222288138
Asan Medical Center ( Site 0200)
Seoul, Seoul-teukbyeolsi [Seoul] 05505
Korea, Republic of
Recruiting Study Coordinator
+82230105614
Chungnam National University Hospital ( Site 0203)
Daejeon, Taejon-Kwangyokshi 35015
Korea, Republic of
Recruiting Study Coordinator
+82422808369
National Cheng Kung University Hospital ( Site 0208)
Tainan, 704
Taiwan
Recruiting Study Coordinator
88662353535
National Taiwan University Hospital ( Site 0210)
Taipei, 10002
Taiwan
Recruiting Study Coordinator
+886966790736
Taipei Veterans General Hospital ( Site 0211)
Taipei, 112
Taiwan
Recruiting Study Coordinator
+886938591266
Istanbul Uni. Cerrahpasa Tip Fakultesi ( Site 0501)
Istanbul, 34098
Turkey
Recruiting Study Coordinator
+905333682319
Clinical oncology dispensary of Dnipro ( Site 0133)
Dnipro, Dnipropetrovska Oblast 49055
Ukraine
Recruiting Study Coordinator
+80687400930
Regional Oncology Center of Kharkiv ( Site 0134)
Kharkiv, Kharkivska Oblast 61000
Ukraine
Recruiting Study Coordinator
+380508266088
National Cancer Institute of the MoH of Ukraine ( Site 0136)
Kyiv, Kyivska Oblast 03022
Ukraine
Recruiting Study Coordinator
+380672365175