AzTrials
AzTrials

Uterine Cervical NeoplasmsPhase 3NCT04221945

Study of Chemoradiotherapy With or Without Pembrolizumab (MK-3475) For The Treatment of Locally Advanced Cervical Cancer (MK-3475-A18/KEYNOTE-A18/ENGOT-cx11/GOG-3047)

A Phase 3 study testing Pembrolizumab, Cisplatin and External Beam Radiotherapy (EBRT) in people with Uterine Cervical Neoplasms, run by Merck Sharp & Dohme LLC at 176 sites in 30 countries.

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

The purpose of this study is to evaluate the efficacy and safety of pembrolizumab plus concurrent chemoradiotherapy compared to placebo plus concurrent chemoradiotherapy in participants with locally advanced cervical cancer. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Uterine Cervical Neoplasms
What is being tested?
Pembrolizumab, Cisplatin and External Beam Radiotherapy (EBRT)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,060 participants
Where
176 sitesin 30 countries
Study dates
12 May 2020to 26 Jan 2026
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Has high-risk locally advanced cervical cancer (LACC): The International Federation of Gynecology and Obstetrics (FIGO) 2014 Stage IB2-IIB (with node-positive disease) or FIGO 2014 Stages III-IVA
  • Has histologically-confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix
  • Has not previously received any definitive surgical, radiation, or systemic therapy for cervical cancer, including investigational agents, and is immunotherapy-naïve
  • Female participants must not be pregnant or breastfeeding and agree to use highly effective contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab or placebo and 180 days following the end of chemoradiotherapy 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.
  • Female participants must abstain from breastfeeding during the study intervention period and for at least 120 days after the last dose of pembrolizumab or placebo and 180 days following the end of chemoradiotherapy
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of study treatment
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  • Has provided a tissue sample from a core incisional or excisional biopsy of a tumor lesion
  • Has radiographically evaluable disease, either measurable or non-measurable per RECIST 1.1, as assessed by the local site investigator/radiology
  • Has adequate organ function within 7 days prior to the start of study treatment.

Who cannot join

  • Has excluded subtypes of LACC
  • Has FIGO 2014 Stage IVB disease
  • Has undergone a previous hysterectomy defined as removal of the entire uterus or will have a hysterectomy as part of their initial cervical cancer therapy
  • Has bilateral hydronephrosis, unless at least one side has been stented or resolved by positioning of nephrostomy or considered mild and not clinically significant in the opinion of the investigator
  • Has anatomy or tumor geometry or any other reason or contraindication that cannot be treated with intracavitary brachytherapy or a combination of intracavitary and interstitial brachytherapy
  • Has received a live vaccine within 30 days prior to the first dose of study treatment
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  • Has received treatment with systemic immunostimulatory agents, colony stimulating factors, interferons, interleukins and vaccine combinations within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1
  • Has received prior therapy with an anti-programmed cell death receptor 1 (PD-1), anti-programmed cell death receptor ligand 1 (PD-L1), or anti-programmed cell death receptor ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137)
  • Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to randomization
  • 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 randomization
  • Has any contraindication to the use of cisplatin
  • 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 treatment
  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
  • Has severe hypersensitivity to pembrolizumab and/or any of its excipients
  • Has an active autoimmune disease that has required systemic treatment in past 2 years
  • Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
  • 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 history or current evidence of any condition, therapy, lab abnormality, or other circumstance that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results, and in the judgment of the investigator or Sponsor, would make the participant inappropriate for entry into this study
  • 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
  • Has evidence of metastatic disease per RECIST 1.1 including lymph nodes above the first lumbar vertebra (L1) cephalad body, in the inguinal region

Trial locations and contacts

176 sites in 30 countries.

176 sites in 30 countries

United States28 sites

  • University of New Mexico Comprehensive Cancer Center-Clinical Research Office ( Site 0019)

    Albuquerque, New Mexico, 87106

  • Texas Oncology-Austin Central ( Site 8006)

    Austin, Texas, 78731

  • Our Lady of the Lake Regional Medical Center. ( Site 0031)

    Baton Rouge, Louisiana, 70817

  • Sanford Bismarck Medical Center ( Site 0046)

    Bismarck, North Dakota, 58501

  • University of North Carolina at Chapel Hill ( Site 0025)

    Chapel Hill, North Carolina, 27514

  • Hollings Cancer Center ( Site 0007)

    Charleston, South Carolina, 29425

  • UVA Health System ( Site 0005)

    Charlottesville, Virginia, 22908

  • The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C

    Columbus, Ohio, 43210

  • Women's Cancer Care ( Site 0039)

    Covington, Louisiana, 70433

  • University of Colorado Health Sciences Center and Hospital ( Site 0028)

    Denver, Colorado, 80262

  • Karmanos Cancer Institute ( Site 0018)

    Detroit, Michigan, 48201

  • Willamette Valley Cancer Institute and Research Center ( Site 8000)

    Eugene, Oregon, 97401

  • Parkview Research Center at Parkview Regional Medical Center ( Site 0026)

    Fort Wayne, Indiana, 46845

  • Texas Oncology-Fort Worth Cancer Center ( Site 8001)

    Fort Worth, Texas, 76104

  • University of Kentucky Markey Cancer Center ( Site 0015)

    Lexington, Kentucky, 40536

  • UCLA Hematology/Oncology - Westwood (Building 200 Suite 120) ( Site 0027)

    Los Angeles, California, 90095

  • Minnesota Oncology Hematology, PA ( Site 8007)

    Minneapolis, Minnesota, 55404

  • Smilow Cancer Center at Yale-New Haven ( Site 0023)

    New Haven, Connecticut, 06510

  • Hoag Memorial Hospital Presbyterian ( Site 0038)

    Newport Beach, California, 92663

  • AdventHealth Orlando-AdventHealth Medical Group Gynecological Oncology ( Site 0009)

    Orlando, Florida, 32804

  • HonorHealth Research Institute - Biltmore ( Site 8009)

    Phoenix, Arizona, 85016

  • Allegheny Health Network West Penn Hospital-Gynecologic Oncology ( Site 0030)

    Pittsburgh, Pennsylvania, 15244

  • Legacy Good Samaritan Medical Center ( Site 0013)

    Portland, Oregon, 97210

  • Virginia Commonwealth University ( Site 0024)

    Richmond, Virginia, 23219

  • UC Davis Comprehensive Cancer Center ( Site 0017)

    Sacramento, California, 95817

  • Texas Oncology-San Antonio Medical Center ( Site 8002)

    San Antonio, Texas, 78240

  • Sanford Gynecology Oncology ( Site 0003)

    Sioux Falls, South Dakota, 57104

  • Texas Oncology-The Woodlands ( Site 8003)

    The Woodlands, Texas, 77380

Other trials in United States

Japan17 sites

  • National Hospital Organization Kyushu Cancer Center ( Site 1167)

    Fukuoka, 811-1395

  • Saitama Medical University International Medical Center ( Site 1168)

    Hidaka, Saitama, 350-1298

  • Kagoshima City Hospital ( Site 1166)

    Kagoshima, 890-8760

  • National Cancer Center Hospital East ( Site 1159)

    Kashiwa, Chiba, 2778577

  • Saitama Cancer Center ( Site 1169)

    Kitaadachi-gun, Saitama, 362-0806

  • Kurume University Hospital ( Site 1164)

    Kurume, Fukuoka, 830-0011

  • National Hospital Organization Shikoku Cancer Center ( Site 1162)

    Matsuyama, Ehime, 791-0280

  • Kyorin University Hospital ( Site 1158)

    Mitaka, Tokyo, 181-8611

  • Aichi Cancer Center Hospital ( Site 1155)

    Nagoya, Aichi-ken, 464-8681

  • University of the Ryukyus Hospital ( Site 1156)

    Nakagami-gun, Okinawa, 903-0215

  • Osaka International Cancer Institute ( Site 1161)

    Osaka, 541-8567

  • Hokkaido University Hospital ( Site 1163)

    Sapporo, Hokkaido, 060-8648

  • Iwate Medical University Hospital ( Site 1165)

    Shiwa-gun, Iwate, 028-3695

  • National Cancer Center Hospital ( Site 1172)

    Tokyo, 104-0045

  • Japanese Foundation for Cancer Research-Gynecologic Oncology ( Site 1171)

    Tokyo, 135-8550

  • Keio University Hospital ( Site 1170)

    Tokyo, 160-8582

  • Ehime University Hospital ( Site 1157)

    Tōon, Ehime, 790-0295

Other trials in Japan

China16 sites

  • Peking Union Medical College Hospital ( Site 1001)

    Beijing, Beijing Municipality, 100730

  • Hunan Cancer Hospital ( Site 1015)

    Changsha, Hunan, 233004

  • Xiangya Hospital Central-South University ( Site 1009)

    Changsha, Hunan, 410008

  • Sichuan Cancer Hospital ( Site 1018)

    Chengdu, Sichuan, 610041

  • Chongqing Cancer Hospital ( Site 1030)

    Chongqing, Chongqing Municipality, 400030

  • The First Affiliated Hospital.Sun Yat-sen University ( Site 1005)

    Guangzhou, Guangdong, 510080

  • Zhejiang Provincial People's Hospital ( Site 1021)

    Hangzhou, Zhejiang, 310014

  • Zhejiang Cancer Hospital ( Site 1004)

    Hangzhou, Zhejiang, 310022

  • Harbin Medical University Cancer Hospital ( Site 1013)

    Harbin, Heilongjiang, 150081

  • Anhui Provincial Hospital ( Site 1029)

    Hefei, Anhui, 230001

  • Anhui Provincial Cancer Hospital ( Site 1007)

    Hefei, Anhui, 230031

  • Affiliated Cancer Hospital of Guangxi Medical University ( Site 1036)

    Nanning, Guangxi, 530021

  • Shanghai Cancer Hospital ( Site 1000)

    Shanghai, Shanghai Municipality, 200032

  • Shanghai First Maternity and Infant Hospital-Gynecology department ( Site 1039)

    Shanghai, Shanghai Municipality, 201204

  • The First Affiliated Hospital of Xinjiang Medical University ( Site 1012)

    Ürümqi, Xinjiang, 830054

  • The First Affiliated Hospital of Xiamen University ( Site 1025)

    Xiamen, Fujian, 361003

Other trials in China

Italy10 sites

  • A.O. Universitaria Policlinico S. Orsola-Malpighi ( Site 0541)

    Bologna, 40138

  • Istituto di Candiolo - IRCCS ( Site 0546)

    Candiolo, Piedmont, 10060

  • Ospedale Vito Fazzi ( Site 0547)

    Lecce, 73100

  • Istituto Europeo di Oncologia ( Site 0536)

    Milan, Milano, 20141

  • IRCCS Ospedale San Raffaele ( Site 0539)

    Milan, 20132

  • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0542)

    Milan, 20133

  • Fondazione Giovanni Pascale Di Napoli ( Site 0544)

    Naples, 80131

  • Policlinico Universitario Gemelli ( Site 0538)

    Roma, 00168

  • Istituto Nazionale Tumori Regina Elena ( Site 0540)

    Rome, Roma, 00144

  • A.O.U. Citta della Salute e della Scienza di Torino ( Site 0535)

    Torino, 10126

Other trials in Italy

Germany8 sites

  • Charite Universitaetsmedizin Berlin ( Site 0442)

    Berlin, 13353

  • Universitaetsklinikum Carl Gustav Carus der Technischen Univ ( Site 0452)

    Dresden, Saxony, 01307

  • Universitaetsklinikum Freiburg ( Site 0454)

    Freiburg im Breisgau, Baden-Wurttemberg, 79106

  • Universitaetsklinikum Hamburg-Eppendorf ( Site 0445)

    Hamburg, 20246

  • Universitaetsklinik Leipzig ( Site 0456)

    Leipzig, Saxony, 04103

  • Universitätsmedizin Mannheim-Department of Obstetrics and Gynecology ( Site 0443)

    Mannheim, Baden-Wurttemberg, 68167

  • Klinikum der Universitaet in Muenchen ( Site 0446)

    Munich, Bavaria, 80336

  • Klinikum Rechts der Isar. Technischen Universitaet Muenchen ( Site 0453)

    Munich, Bavaria, 81675

Other trials in Germany

Peru7 sites

  • Centro Medico Monte Carmelo ( Site 0289)

    Arequipa, Ariqipa, 04001

  • Hospital Nacional Daniel Alcides Carrion ( Site 0293)

    Callao, Lima, 07021

  • Instituto de Oncologia y Radioterapia Clinica Ricardo Palma ( Site 0290)

    Lima, 15036

  • Hospital Nacional Arzobispo Loayza ( Site 0292)

    Lima, 15082

  • Hospital Nacional Guillermo Almenara Irigoyen ( Site 0291)

    Lima, 15082

  • Clinica San Gabriel ( Site 0296)

    San Miguel, Lima region, 15087

  • Hospital de Alta Complejidad de La Libertad Virgen de La Puerta ( Site 0287)

    Trujillo, La Libertad, 13013

Other trials in Peru

Belgium6 sites

  • OLV Ziekenhuis ( Site 0352)

    Aalst, Oost-Vlaanderen, 9300

  • UZA University Hospital Antwerp ( Site 0351)

    Edegem, Antwerpen, 2650

  • AZ St Lucas ( Site 0349)

    Ghent, Oost-Vlaanderen, 9000

  • UZ Leuven ( Site 0354)

    Leuven, Vlaams-Brabant, 3000

  • C.I.U. Hopital Ambroise Pare ( Site 0353)

    Mons, Hainaut, 7000

  • GZA Sint Augustinus ( Site 0356)

    Wilrijk, Antwerpen, 2610

Other trials in Belgium

Guatemala6 sites

  • Centro de Investigaciones Clinicas de Latinoamerica S.A. - CELAN ( Site 0321)

    Guatemala City, 01010

  • Oncologika S.A. ( Site 0323)

    Guatemala City, 01010

  • Oncomedica ( Site 0320)

    Guatemala City, 01010

  • Grupo Angeles SA ( Site 0319)

    Guatemala City, 01015

  • Medi-K Cayala ( Site 0318)

    Guatemala City, 01016

  • Centro Medico Integral De Cancerología (CEMIC) ( Site 0322)

    Quetzaltenango, 09002

Other trials in Guatemala

Russia6 sites

  • Chelyabinsk Regional Clinical Center Oncology and Nuclear Medicine ( Site 0741)

    Chelyabinsk, Chelyabinsk Oblast, 454087

  • Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0729)

    Krasnoyarsk, Krasnoyarsk Krai, 660133

  • MSROI named after P.A. Hertsen branch of FSBI NMRC Radiology ( Site 0722)

    Moscow, Moscow, 125284

  • GBUZ SPb CRPCstmc(o) ( Site 0746)

    Saint Petersburg, Sankt-Peterburg, 197758

  • National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 0725)

    Saint Petersburg, Sankt-Peterburg, 197758

  • Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 0734)

    Yaroslavl, Yaroslavl Oblast, 150054

Other trials in Russia

Spain6 sites

  • Hospital Germans Trias i Pujol-Instituto Catalán de Oncología de Badalona ( Site 0637)

    Badalona, Barcelona, 08916

  • Hospital Universitari Vall d Hebron ( Site 0634)

    Barcelona, 08035

  • Complejo Hospitalario de Jaen ( Site 0632)

    Jaén, 23007

  • HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID-ONCOLOGIA MEDICA ( Site 0638)

    Pozuelo de Alarcón, Madrid, 28223

  • Hosp Clin Univ de Santiago ( Site 0629)

    Santiago de Compostela, La Coruna, 15706

  • Hospital Clinico Universitario Lozano Blesa ( Site 0630)

    Zaragoza, 50009

Other trials in Spain

Australia5 sites

  • Monash Health-Monash Medical Centre ( Site 0970)

    Clayton, Victoria, 3168

  • Royal Brisbane and Women s Hospital ( Site 0972)

    Herston, Queensland, 4029

  • Peter MacCallum Cancer Centre ( Site 0971)

    Melbourne, Victoria, 3000

  • St John of God Subiaco Hospital ( Site 0969)

    Subiaco, Western Australia, 6008

  • Westmead Hospital ( Site 0973)

    Westmead, New South Wales, 2145

Other trials in Australia

Brazil5 sites

  • Hospital das Clinicas da UFMG ( Site 0172)

    Belo Horizonte, Minas Gerais, 30130-100

  • Liga Norte Riograndense Contra o Cancer ( Site 0170)

    Natal, Rio Grande do Norte, 59075-740

  • Hospital de Clínicas de Ribeirão Preto ( Site 0171)

    Ribeirão Preto, São Paulo, 14048900

  • Instituto Nacional Do Cancer II ( Site 0173)

    Rio de Janeiro, 20220-410

  • Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 0166)

    São Paulo, São Paulo, 04014-002

Other trials in Brazil

South Korea5 sites

  • Keimyung University Dongsan Medical Center ( Site 1066)

    Daegu, Taegu-Kwangyokshi, 42601

  • National Cancer Center ( Site 1065)

    Goyang-si, Kyonggi-do, 10408

  • Asan Medical Center ( Site 1062)

    Seoul, Seoul, 05505

  • Severance Hospital ( Site 1063)

    Seoul, 03722

  • Samsung Medical Center ( Site 1064)

    Seoul, 06351

Other trials in South Korea

Canada4 sites

  • Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0101)

    Montreal, Quebec, H2X 0A9

  • McGill University Health Centre ( Site 0105)

    Montreal, Quebec, H4A 3J1

  • Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0

    Québec, Quebec, G1J 1Z4

  • Princess Margaret Cancer Centre ( Site 0102)

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Chile4 sites

  • Sociedad Oncovida S.A. ( Site 0196)

    Santiago, Region M. de Santiago, 7510032

  • Iram Cancer Research ( Site 0198)

    Santiago, Region M. de Santiago, 7630370

  • Centro Investigación del Cáncer James Lind ( Site 0194)

    Temuco, Araucania, 4800827

  • Oncocentro ( Site 0195)

    Viña del Mar, Valparaiso

Other trials in Chile

Colombia4 sites

  • Instituto Nacional de Cancerologia E.S.E ( Site 0228)

    Bogotá, Bogota D.C., 110321

  • Fundacion Valle del Lili ( Site 0230)

    Cali, Valle del Cauca Department, 760032

  • Centro Medico Imbanaco de Cali S.A ( Site 0227)

    Cali, Valle del Cauca Department, 760042

  • Fundacion Centro de Investigacion Clinica CIC ( Site 0231)

    Medellín, Antioquia, 050021

Other trials in Colombia

Greece4 sites

  • Alexandra General Hospital ( Site 0477)

    Athens, Attica, 11528

  • Hospital Hygeia ( Site 0478)

    Athens, Attica, 151 23

  • General Hospital of Patras. St Andrews ( Site 0473)

    Pátrai, Achaia, 262 00

  • Euromedica General Clinic of Thessaloniki ( Site 0474)

    Thessaloniki, 546 45

Other trials in Greece

Israel4 sites

  • Rambam Medical Center ( Site 0815)

    Haifa, 3109601

  • Hadassah Medical Center. Ein Kerem ( Site 0816)

    Jerusalem, 9112001

  • Chaim Sheba Medical Center ( Site 0814)

    Ramat Gan, 5262000

  • Sourasky Medical Center ( Site 0819)

    Tel Aviv, 6423906

Other trials in Israel

Thailand4 sites

  • Maharaj Nakorn Chiang Mai Hospital ( Site 1133)

    Chiang Mai, 50200

  • Songklanagarind Hospital ( Site 1130)

    Hat Yai, Changwat Songkhla, 90110

  • Srinagarind Hospital. Khon Kaen University ( Site 1132)

    Mueang, Changwat Khon Kaen, 40002

  • Ramathibodi Hospital, Mahidol University ( Site 1131)

    Rajthevee, Bangkok, 10400

Other trials in Thailand

Austria3 sites

  • Medizinische Universitat Graz ( Site 0569)

    Graz, Styria, 8036

  • Medizinische Universitat Innsbruck ( Site 0566)

    Innsbruck, Tyrol, 6020

  • Medizinische Universität Wien ( Site 0567)

    Vienna, State of Vienna, 1090

Other trials in Austria

Czechia3 sites

  • Fakultni Nemocnice Brno Bohunice ( Site 0912)

    Brno, Brno-mesto, 602 00

  • Fakultni nemocnice Ostrava ( Site 0909)

    Ostrava, Moravian-Silesian Region, 708 52

  • Fakultni nemocnice Kralovske Vinohrady ( Site 0913)

    Prague, 100 34

Other trials in Czechia

France3 sites

  • CHU Jean Minjoz ( Site 0411)

    Besançon, Doubs, 25000

  • Centre Hospitalier Lyon Sud ( Site 0413)

    Pierre-Bénite, Rhone, 69310

  • Institut Claudius Regaud ( Site 0417)

    Toulouse, Haute-Garonne, 31059

Other trials in France

Taiwan3 sites

  • National Taiwan University Hospital ( Site 1095)

    Taipei, 100

  • Mackay Memorial Hospital ( Site 1094)

    Taipei, 104

  • Linkou Chang Gung Memorial Hospital ( Site 1097)

    Taoyuan, 333

Other trials in Taiwan

Turkey (Türkiye)3 sites

  • Acibadem Adana Hastanesi ( Site 0756)

    Adana, 01130

  • Baskent Universitesi Ankara Hastanesi ( Site 0754)

    Ankara, 06490

  • I.U. Cerrahpasa Medical Faculty ( Site 0755)

    Istanbul, Istanbul, 34093

Other trials in Turkey (Türkiye)

United Kingdom3 sites

  • Royal Devon and Exeter Foundation Trust Hospital ( Site 0699)

    Exeter, England

  • ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 0701)

    London, London, City of, SW3 6JJ

  • Royal Marsden Hospital (Sutton)-Gynaecology Unit ( Site 0696)

    London, Surrey, SM3 5PT

Other trials in United Kingdom

Hungary2 sites

  • Orszagos Onkologiai Intezet ( Site 0846)

    Budapest, 1122

  • Debreceni Egyetem Klinikai Kozpont ( Site 0845)

    Debrecen, 4032

Other trials in Hungary

Ireland2 sites

  • Cork University Hospital ( Site 0504)

    Cork, T12 DC4A

  • St James Hospital ( Site 0505)

    Dublin, D8

Other trials in Ireland

Norway2 sites

  • Helse Bergen HF Haukeland Universitetssjukehus ( Site 0601)

    Bergen, Hordaland, 5021

  • Oslo Universitetssykehus Radiumhospitalet ( Site 0600)

    Oslo, 0379

Other trials in Norway

Ukraine2 sites

  • Grigoriev Institute for medical Radiology NAMS of Ukraine ( Site 0876)

    Kharkiv, Kharkiv Oblast, 61024

  • Lviv State Oncology Regional Treatment and Diagnostic Center ( Site 0882)

    Lviv, Lviv Oblast, 79031

Other trials in Ukraine

Sweden1 site

  • Karolinska Universitetssjukhuset ( Site 0784)

    Stockholm, Stockholm County, 171 76

Other trials in Sweden

About this study

Official title: A Randomized, Phase 3, Double-Blind Study of Chemoradiotherapy With or Without Pembrolizumab for the Treatment of High-risk, Locally Advanced Cervical Cancer (KEYNOTE-A18/ENGOT-cx11/GOG-3047)

The purpose of this study is to evaluate the efficacy and safety of pembrolizumab plus concurrent chemoradiotherapy compared to placebo plus concurrent chemoradiotherapy in participants with locally advanced cervical cancer.

The primary hypotheses are that pembrolizumab plus concurrent chemoradiotherapy is superior to placebo plus concurrent chemoradiotherapy with respect to progression-free survival and overall survival.

Once the study objectives have been met or the study has ended, participants will be discontinued from this study and will be enrolled in an extension study to continue protocol-defined assessments and treatment.

Being tested
Pembrolizumab, Placebo for pembrolizumab, Cisplatin, External Beam Radiotherapy (EBRT), Brachytherapy
Keywords
Programmed Cell Death Receptor 1 (PD-1, PD1), Programmed Cell Death Receptor Ligand 1 (PD-L1, PDL1), Programmed Cell Death Receptor Ligand 2 (PD-L2, PDL2)
Medical subject headings
Uterine Cervical Neoplasms, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

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

  • PembrolizumabBiological

    Also called KEYTRUDA®, MK-3475

    IV infusion

  • Placebo for pembrolizumabDrug

    IV infusion

  • CisplatinDrug

    Also called Platinol®, Platinol®-AQ

    IV infusion

  • External Beam Radiotherapy (EBRT)Radiation

    Given as a total radiotherapy dose of 80 Gy for volume-directed and 75 Gy for point-directed

  • BrachytherapyRadiation

    Given as a total radiotherapy dose of 80 Gy for volume-directed and 75 Gy for point-directed

Study groups in NCT04221945
Study groupRoleWhat they receive
chemoradiotherapy + pembrolizumabExperimentalParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for 5 cycles followed by pembrolizumab 400 mg IV on Day 1 of each 6-week cycle (Q6W) for an additional 15 cycles. During the Q3W dosing period of pembrolizumab, participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m^2 IV once per week (QW) for 5 or 6 weeks plus external beam radiotherapy (EBRT) followed by brachytherapy with minimum total radiotherapy dose of 80 Gray Units (Gy) for volume-directed and 75 Gy for point-directed given with the total duration of radiation treatment not to exceed 50 days (with an extension to a maximum of 56 days for unforeseen delays).
Receives: Biological: Pembrolizumab; Drug: Cisplatin; Radiation: External Beam Radiotherapy (EBRT); Radiation: Brachytherapy
chemoradiotherapy + placebo for pembrolizumabExperimentalParticipants receive placebo for pembrolizumab IV on Day 1 of each 3-week cycle (Q3W) for 5 cycles followed by placebo IV on Day 1 of each 6-week cycle (Q6W) for an additional 15 cycles. During the Q3W dosing period of placebo, participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m^2 IV once per week (QW) for 5 or 6 weeks plus external beam radiotherapy (EBRT) followed by brachytherapy with minimum total radiotherapy dose of 80 Gray Units (Gy) for volume-directed and 75 Gy for point-directed given with the total duration of radiation treatment not to exceed 50 days (with an extension to a maximum of 56 days for unforeseen delays).
Receives: Drug: Placebo for pembrolizumab; Drug: Cisplatin; Radiation: External Beam Radiotherapy (EBRT); Radiation: Brachytherapy

What is being measured

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

  1. Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator

    PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, or by histopathologic confirmation of suspected disease progression, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. Unequivocal progression of non-target lesions is also considered PD. The Kaplan-Meier nonparametric product limit method for censored data was used to estimate PFS.

    Measured: Up to approximately 55 months

  2. Overall Survival (OS)

    OS is the time from randomization to death due to any cause. The Kaplan-Meier nonparametric product limit method for censored data was used to estimate OS.

    Measured: Up to approximately 55 months

Secondary outcomes (17)

  1. PFS Per RECIST 1.1 as Assessed by Blinded Independent Central Review (BICR)

    PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. Unequivocal progression of non-target lesions is also considered PD. The Kaplan-Meier nonparametric product limit method for censored data was used to estimate PFS.

    Measured: Up to approximately 55 months

  2. PFS Per RECIST 1.1 at Month 24 as Assessed by the Investigator

    PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, or by histopathologic confirmation of suspected disease progression, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. Unequivocal progression of non-target lesions is also considered PD. The percentage of participants with PFS as assessed by the investigator is presented.

    Measured: 24 months

  3. PFS Per RECIST 1.1 at Month 24 as Assessed by BICR

    PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. Unequivocal progression of non-target lesions is also considered PD. The percentage of participants with PFS as assessed by BICR is presented.

    Measured: 24 months

  4. Overall Survival (OS) at Month 36

    OS is the time from randomization to death due to any cause. The analysis was performed via Kaplan-Meier approach to estimate the OS rate at Month 36. The percentage of participants with OS at Month 36 is presented.

    Measured: 36 months

  5. Complete Response (CR) Rate Per RECIST 1.1 at Week 12 as Assessed by the Investigator

    For participants who demonstrated a confirmed Complete Response (CR: Disappearance of all target and non-target lesions and also includes reduction of all nodal lesions to <10mm) per RECIST 1.1, CR rate is defined as the percentage of participants who experienced a CR. The percentage of participants with CR per RECIST 1.1 as assessed by the investigator at Week 12 is presented.

    Measured: 12 weeks

  6. CR Rate Per RECIST 1.1 at Week 12 as Assessed by BICR

    For participants who demonstrated a confirmed CR: Disappearance of all target and non-target lesions and also includes reduction of all nodal lesions to <10mm) per RECIST 1.1, CR rate is defined as the percentage of participants who experienced a CR. The percentage of participants with CR per RECIST 1.1 as assessed by BICR at Week 12 is presented.

    Measured: 12 weeks

  7. Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by the Investigator

    ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target and non-target lesions and also includes reduction of all nodal lesions to <10mm) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions and includes no unequivocal progression in non-target lesions) per RECIST 1.1.

    Measured: Up to approximately 55 months

  8. ORR Per RECIST 1.1 as Assessed by BICR

    ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target and non-target lesions and also includes reduction of all nodal lesions to <10mm) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions and includes no unequivocal progression in non-target lesions) per RECIST 1.1.

    Measured: Up to approximately 55 months

  9. PFS Per RECIST 1.1 in Programmed Cell Death 1 Ligand 1 (PD-L1) Positive Participants as Assessed by the Investigator

    PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, or by histopathologic confirmation of suspected disease progression, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. Unequivocal progression of non-target lesions is also considered PD. PD-L1 positive participants have a combined positivity score (CPS) equal or greater than 1. The Kaplan-Meier nonparametric product limit method for censored data was used to estimate PFS.

    Measured: Up to approximately 55 months

  10. PFS Per RECIST 1.1 in PD-L1 Positive Participants as Assessed by BICR

    PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. Unequivocal progression of non-target lesions is also considered PD. PD-L1 positive participants have a CPS equal or greater than 1. The Kaplan-Meier nonparametric product limit method for censored data was used to estimate PFS.

    Measured: Up to approximately 55 months

  11. OS in PD-L1 Positive Participants

    OS is the time from randomization to death due to any cause. PD-L1 positive participants have a CPS equal or greater than 1. The Kaplan-Meier nonparametric product limit method for censored data was used to estimate OS.

    Measured: Up to approximately 55 months

  12. PFS After Next-Line Treatment (PFS 2) Following Discontinuation of Study Treatment

    PFS is defined as the time from randomization to the first documented progressive disease (PD) on next-line treatment or death due to any cause, whichever occurs first, as assessed by the investigator. PFS 2 is measured after next-line treatment following discontinuation of study treatment administration.

    Measured: Up to approximately 55 months

  13. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score

    The EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. The change from baseline in EORTC QLQ-C30 score will be presented.

    Measured: Baseline and week 36

  14. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Function Score

    The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=not at all to 4=very much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better quality of life. The change from baseline in physical function (EORTC QLQ-C30 Items 1-5) score will be presented.

    Measured: Baseline and week 36

  15. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Symptom Specific Scale for Cervical Cancer (EORTC QLQ-CX24) Score

    The EORTC QLQ-CX24 is a questionnaire that rates the symptoms common to women with cervical cancer and evaluates the impact of disease and/or treatments. The 24 items use a 4-point scale (1=not at all to 4=very much) and are classified into 3 multi-item scales, 11 items with symptom experience, 3 items with body image, and 4 items with sexual/ vaginal functioning. The other items of the questionnaire are lymphedema, peripheral neuropathy, menopausal symptom, sexual worry, sexual activity, and sexual enjoyment. Total scores are linearly transformed and range from 0 (no symptoms) to 100 (most severe symptoms). The change from baseline in EORTC QLQ-CX24 score is presented, with negative scores representing an improvement from baseline and vice versa.

    Measured: Baseline and Week 36

  16. Number of Participants Who Experience One or More Adverse Events (AEs)

    An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.

    Measured: Up to 55 months

  17. Number of Participants Who Discontinue Study Treatment Due to an AE

    An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.

    Measured: Up to 32 months

Timeline

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

  1. First posted9 Jan 2020
  2. Study start12 May 2020
  3. Primary completion7 Jan 2025
  4. Study completion26 Jan 2026

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
1,060 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04221945
Sponsor's protocol ID
3475-A18
Other IDs
MK-3475-A18, KEYNOTE-A18, ENGOT-cx11, 205189, GOG-3047, 2022-501972-25-00, U1111-1282-6395, 2019-003152-37
Status last verified
Oct 2026
First submitted
23 Dec 2019
Last updated
5 Nov 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

  • Lorusso D, Xiang Y, Hasegawa K, Scambia G, Leiva M, Ramos-Elias P, Acevedo A, Sukhin V, Cloven N, Pereira de Santana Gomes AJ, Contreras Mejia F, Reiss A, Ayhan A, Lee JY, Saevets V, Zagouri F, Gilbert L, Sehouli J, Tharavichitkul E, Lindemann K, Lazzari R, Chang CL, Lampe R, Zhu H, Oaknin A, Christiaens M, Polterauer S, Usami T, Li K, Yamada K, Toker S, Keefe SM, Pignata S, Duska LR; ENGOT-cx11/GOG-3047/KEYNOTE-A18 investigators. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial. Lancet. 2024 Apr 6;403(10434):1341-1350. doi: 10.1016/S0140-6736(24)00317-9. Epub 2024 Mar 20.

    PubMed 38521086

  • Lorusso D, Xiang Y, Hasegawa K, Scambia G, Leiva M, Ramos-Elias P, Acevedo A, Cvek J, Randall L, Pereira de Santana Gomes AJ, Contreras Mejia F, Helpman L, Akilli H, Lee JY, Saevets V, Zagouri F, Gilbert L, Sehouli J, Tharavichitkul E, Lindemann K, Colombo N, Chang CL, Bednarikova M, Zhu H, Oaknin A, Christiaens M, Petru E, Usami T, Liu P, Yamada K, Toker S, Keefe SM, Pignata S, Duska LR; ENGOT-cx11/GOG-3047/KEYNOTE-A18 investigators. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024 Oct 5;404(10460):1321-1332. doi: 10.1016/S0140-6736(24)01808-7. Epub 2024 Sep 14.

    PubMed 39288779

  • Randall L, Xiang Y, Matsumoto T, Giannarelli D, Milla DP, Lopez KA, Acevedo A, Vizkeleti J, Salani R, Nogueira-Rodrigues A, Mejia FC, Korach J, Akilli H, Lee JY, Saevets VV, Samouelian V, Sehouli J, Tharavichikul E, Sukhin V, Colombo N, Chang CL, Cueva JF, Lalondrelle S, Petru E, Szamreta E, Nguyen AM, Yamada K, Li K, Pignata S, Lorusso D. Patient-reported outcomes from the phase 3, randomized, double-blind, placebo-controlled ENGOT-cx11/GOG-3047/KEYNOTE-A18 study of pembrolizumab plus concurrent chemoradiotherapy in participants with high-risk locally advanced cervical cancer. Gynecol Oncol. 2025 Aug;199:88-95. doi: 10.1016/j.ygyno.2025.06.003. Epub 2025 Jun 30.

    PubMed 40592026

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pembrolizumab, Cisplatin and External Beam Radiotherapy (EBRT) in people with Uterine Cervical Neoplasms, run by Merck Sharp & Dohme LLC at 176 sites in 30 countries.

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 9 inclusion and 23 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 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 176 sites in United States, Japan, China, Italy, Germany and 25 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator (time frame: Up to approximately 55 months). The study lists 2 primary outcomes in all. 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 NCT04221945, which also lists 3 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 5 Nov 2026.

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