Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy (ADRIATIC)

A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center, International Study of Durvalumab or Durvalumab and Tremelimumab as Consolidation Treatment for Patients With Limited Stage Small Cell Lung Cancer Who Have Not Progressed Following Concurrent Chemoradiation Therapy (ADRIATIC)

This is a Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center, International Study of Durvalumab or Durvalumab and Tremelimumab as Consolidation Treatment for Patients with LS-SCLC Who Have Not Progressed Following Concurrent Chemoradiation Therapy

Study Overview

• Status: Active, not recruiting
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Drug: Durvalumab; Other: Placebo; Drug: Tremelimumab

• Study Type: Interventional
• Enrollment (Actual): 730
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Caba, Argentina, C1012AAR
    • Research Site
  • Caba, Argentina, C1280AEB
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  • Córdoba, Argentina, X5004BAL
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  • Mar del Plata, Argentina, 7600
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  • Rosario, Argentina, 2000
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• Belgium
  • Aalst, Belgium, 9300
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  • Anderlecht, Belgium, 1070
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  • Bruxelles, Belgium, 1200
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  • Hasselt, Belgium, 3500
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  • Roeselare, Belgium, 8800
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• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
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  • CA
    • Toronto, CA, Canada, M5G 2M9
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  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
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  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
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    • London, Ontario, Canada, N6A 5W9
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    • Ottawa, Ontario, Canada, K1H 8L6
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    • Toronto, Ontario, Canada, M4N 3M5
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  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
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• China
  • Beijing, China, 100142
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  • Beijing, China, 100021
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  • Beijing, China, 100730
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  • Beijing, China, 100191
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  • Beijing, China, 100036
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  • Bengbu, China, 233060
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  • Changchun, China, 130000
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  • Changsha, China, 410013
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  • Chengdu, China, 610042
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  • Chongqing, China, 400030
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  • Chongqing, China, 400042
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  • Fuzhou, China, 350011
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  • Hangzhou, China, 310003
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  • Hefei, China, 230601
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  • Shanghai, China, 200032
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  • Shanghai, China, 200030
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  • Shenyang, China, 110001
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  • Shenyang, China, 110042
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  • Tianjin, China, 300060
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  • Wuhan, China, 430022
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  • Wuhan, China, 430030
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  • Wuhan, China, 430010
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  • Yangzhou, China, 225001
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  • Zhengzhou, China, 450008
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• Czechia
  • Brno, Czechia, 639 00
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  • Olomouc, Czechia, 775 21
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  • Ostrava, Czechia, 703 00
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  • Praha, Czechia, 140 59
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  • Praha 2, Czechia, 128 08
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• Germany
  • Berlin, Germany, 12351
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  • Freiburg, Germany, 79106
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  • Gauting, Germany, 82131
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  • Gerlingen, Germany, 70839
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  • Heidelberg, Germany, 69126
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  • Köln, Germany, 51109
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  • Mainz, Germany, 55131
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  • Münster, Germany, 48149
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  • Oldenburg, Germany, 26121
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  • Regensburg, Germany, 93053
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  • Wuerzburg, Germany, 97080
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• India
  • Bengaluru, India, 560076
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  • Gurgaon, India, 122001
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• Italy
  • Brescia, Italy, 25123
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  • Milano, Italy, 20141
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  • Milano, Italy, 20133
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  • Orbassano, Italy, 10043
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  • Parma, Italy, 43126
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  • Roma, Italy, 00100
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  • Rozzano, Italy, 20089
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  • Terni, Italy, 05100
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• Japan
  • Bunkyo-ku, Japan, 160-0023
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  • Chuo-ku, Japan, 104-0045
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  • Fukuoka-shi, Japan, 812-8582
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  • Iwakuni-shi, Japan, 740-8510
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  • Kashiwa, Japan, 277-8577
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  • Koto-ku, Japan, 135-8550
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  • Kurume-shi, Japan, 830-0011
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  • Nagoya-shi, Japan, 464-8681
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  • Nagoya-shi, Japan, 466-8560
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  • Niigata-shi, Japan, 951-8566
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  • Osakasayama, Japan, 589-8511
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  • Sakai-shi, Japan, 591-8555
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  • Sapporo-shi, Japan, 003-0804
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  • Sendai-shi, Japan, 980-0873
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  • Sunto-gun, Japan, 411-8777
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  • Tokushima-shi, Japan, 770-8503
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  • Ube-shi, Japan, 755-0241
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• Korea, Republic of
  • Changwon-si, Korea, Republic of, 51353
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  • Cheongju-si, Korea, Republic of, 28644
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  • Daegu, Korea, Republic of, 42415
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  • Goyang-si, Korea, Republic of, 10408
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  • Jinju-si, Korea, Republic of, 52727
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  • Seongnam-si, Korea, Republic of, 13620
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  • Seoul, Korea, Republic of, 03722
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  • Seoul, Korea, Republic of, 05505
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  • Seoul, Korea, Republic of, 03080
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  • Suwon-si, Korea, Republic of, 16499
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• Netherlands
  • Amsterdam, Netherlands, 1081 HV
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  • Den Bosch, Netherlands, 5223 GZ
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  • Groningen, Netherlands, 9713 GZ
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  • Harderwijk, Netherlands, 3844 DG
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  • Hengelo, Netherlands, 7555 DL
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• Poland
  • Gdańsk, Poland, 80-214
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  • Olsztyn, Poland, 10-357
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  • Poznań, Poland, 60-569
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  • Tomaszów Mazowiecki, Poland, 97-200
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  • Warszawa, Poland, 02-781
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  • Wroclaw, Poland, 53-413
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• Russian Federation
  • Kazan, Russian Federation, 420029
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  • Kirov, Russian Federation, 610021
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  • Moscow, Russian Federation, 115478
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  • Moscow, Russian Federation, 125284
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  • Moscow, Russian Federation, 105229
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  • Obninsk, Russian Federation, 249036
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  • Omsk, Russian Federation, 644013
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  • Ufa, Russian Federation, 450054
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  • Volgograd, Russian Federation, 400138
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• Spain
  • Barcelona, Spain, 08035
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  • Barcelona, Spain, 08003
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  • Madrid, Spain, 28034
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  • Madrid, Spain, 28041
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  • Madrid, Spain, 28040
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  • Oviedo, Spain, 33011
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  • Sevilla, Spain, 41013
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  • Valencia, Spain, 46026
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  • Zaragoza, Spain, 50009
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• Taiwan
  • Hsinchu, Taiwan, 300
    • Research Site
  • Kaohsiung City, Taiwan, 83301
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  • Keelung City, Taiwan, 20445
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  • Taichung, Taiwan, 40705
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  • Tainan, Taiwan, 736
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  • Tainan City, Taiwan, 70403
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  • Taipei, Taiwan, 235
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  • Taipei, Taiwan, 112
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  • Taoyuan City, Taiwan, 333
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  • Yunlin, Taiwan, 640
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• Turkey
  • Adana, Turkey, 01060
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  • Ankara, Turkey, 06230
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  • Ankara, Turkey, 06280
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  • Antalya, Turkey, 07059
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  • Edirne, Turkey, 22030
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  • Istanbul, Turkey, 34030
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  • Izmir, Turkey, 35620
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  • Konya, Turkey, 42080
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  • Samsun, Turkey
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• United Kingdom
  • Manchester, United Kingdom, M20 4BX
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  • Truro, United Kingdom, TR1 3LJ
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• United States
  • Arizona
    • Tucson, Arizona, United States, 85715
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  • California
    • Santa Rosa, California, United States, 95403
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  • Connecticut
    • New Haven, Connecticut, United States, 06510
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  • Florida
    • Fort Myers, Florida, United States, 33901
      • Research Site
    • Orange City, Florida, United States, 32763
      • Research Site
    • Saint Petersburg, Florida, United States, 33705
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  • Georgia
    • Marietta, Georgia, United States, 30060
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  • Illinois
    • Hines, Illinois, United States, 60141
      • Research Site
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Research Site
    • Muncie, Indiana, United States, 47303
      • Research Site
  • Kentucky
    • Lexington, Kentucky, United States, 40536
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  • Maryland
    • Annapolis, Maryland, United States, 21401
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    • Baltimore, Maryland, United States, 21287
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    • Towson, Maryland, United States, 21204
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  • Massachusetts
    • Boston, Massachusetts, United States, 02114
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  • Michigan
    • Detroit, Michigan, United States, 48201
      • Research Site
    • Grand Rapids, Michigan, United States, 49503
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  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
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  • New Jersey
    • Summit, New Jersey, United States, 07902
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  • New York
    • New Hyde Park, New York, United States, 11042
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  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
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  • Oregon
    • Portland, Oregon, United States, 97239
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  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
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    • Pittsburgh, Pennsylvania, United States, 15212
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  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
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  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
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    • Nashville, Tennessee, United States, 37203
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    • Nashville, Tennessee, United States, 37232
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  • Texas
    • Dallas, Texas, United States, 75390
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  • Washington
    • Kennewick, Washington, United States, 99336
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    • Tacoma, Washington, United States, 98405
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  • West Virginia
    • Charleston, West Virginia, United States, 25304
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    • Huntington, West Virginia, United States, 25701
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  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
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• Vietnam
  • Hanoi, Vietnam, 100000
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  • Ho Chi Minh, Vietnam, 700000
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  • Ho Chi Minh, Vietnam, 70000
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Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Histologically or cytologically documented limited-stage small cell lung cancer (stage I-III).
2. Received 4 cycles of chemotherapy concurrent with radiotherapy, which must be completed within 1 to 42 days prior to randomization and the first dose of IP. Chemotherapy must contain platinum and IV etoposide. Radiotherapy must be either total 60-66 Gy over 6 weeks for the standard QD regimen or total 45 Gy over 3 weeks for hyperfractionated BD schedules.
3. PCI may be delivered at the discretion of investigator and local standard of care, and must be conducted after the end of cCRT and completed between 1 to 42 days to first dose of IP.

4 .Have not progressed following definitive concurrent chemoradiation 5 .Life expectancy ≥ 12 weeks at Day 1. 6. ECOG 0 or 1 at enrolment.

Exclusion criteria:

1. Extensive-stage SCLC
2. Active or prior documented autoimmune or inflammatory disorders
3. Uncontrolled intercurrent illness, including but not limited to interstitial lung disease.
4. Active infection including tuberculosis, HIV, hepatitis B and C
5. Patients who received sequential chemotherapy and radiotherapy (no overlap of RT with chemotherapy)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Durvalumab + Placebo; Durvalumab monotherapy: Durvalumab (1500 mg intravenous [IV]) q4w in combination with placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with placebo saline solution.	Drug: Durvalumab; Durvalumab IV (intravenous infusion); Other Names: MEDI4736; Other: Placebo; Placebo IV (intravenous infusion)
Experimental: Durvalumab + Tremelimumab; Durvalumab in combination with tremelimumab: Durvalumab (1500 mg IV) q4w in combination with tremelimumab (75 mg IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with tremelimumab.	Drug: Durvalumab; Durvalumab IV (intravenous infusion); Other Names: MEDI4736; Drug: Tremelimumab; Tremelimumab IV (intravenous infusion)
Placebo Comparator: Placebo + Placebo; Placebo: Placebo saline solution (IV) q4w in combination with a second placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by a single placebo saline solution q4w. The first placebo saline solution monotherapy dose q4w will be 4 weeks after the final dose of the 2 placebo saline solutions in combination.	Other: Placebo; Placebo IV (intravenous infusion)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	To assess the efficacy of Durvalumab monotherapy vs Placebo in terms of OS	Approximately 6 years
Progression-free survival (PFS)	To assess the efficacy of Durvalumab monotherapy vs Placebo in terms of PFS	Approximately 6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	To assess the efficacy of Durvalumab & Tremelimumab combination therapy vs Placebo in terms of OS	Approximately 6 years
Objective Response Rate (ORR)		Approximately 6 years
Time to death or distant metastasis (TTDM)		Approximately 6 years
Proportion of patients alive at 24 months (OS24)		Approximately 6 years
Proportion of patients alive at and 36 months (OS36)		Approximately 6 years
Time from randomization to second progression (PFS2)		Approximately 6 years
To assess symptoms and health-related QoL in patients treated withdurvalumab or durvalumab and tremelimumab combination therapy compared to placebo using the EORTC QLQ-C30 v3		Approximately 6 years
To assess the PK of durvalumab and tremelimumab in blood (peak trough concentration)		Approximately 6 years
Presence of anti-drug antibodies (ADA) for durvalumab and tremelimumab (confirmatory results: positive or negative)		Approximately 6 years
PD-L1 expression in tumor and/or immune cells relative to response/efficacy outcomes (PFS, OS & ORR).	To investigate the relationship between PDL1 expression & spatial distribution with Durva (mono) therapy & Durva+Treme (combination) therapy	Approximately 6 years
To assess symptoms and health-related QoL in patients treated withdurvalumab or durvalumab and tremelimumab combination therapy compared to placebo using the EORTC QLQ-LC13		Approximately 6 years
Progression-free survival PFS	To assess the efficacy of durvalumab and tremelimumab combination therapy compared to placebo in terms of PFS	Approximately 6 years
Progression-free survival at 18 months (PFS18)		Approximately 6 years
Progression-free survival at 24 months (PFS24)		Approximately 6 years

Other Outcome Measures

Outcome Measure	Time Frame
Adverse Events	Approximately 6 years

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Haiyi Jiang, M.D., AstraZeneca

Publications and helpful links

General Publications

• Senan S, Okamoto I, Lee GW, Chen Y, Niho S, Mak G, Yao W, Shire N, Jiang H, Cho BC. Design and Rationale for a Phase III, Randomized, Placebo-controlled Trial of Durvalumab With or Without Tremelimumab After Concurrent Chemoradiotherapy for Patients With Limited-stage Small-cell Lung Cancer: The ADRIATIC Study. Clin Lung Cancer. 2020 Mar;21(2):e84-e88. doi: 10.1016/j.cllc.2019.12.006. Epub 2019 Dec 28.

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2018
• Primary Completion (Estimated): September 5, 2024
• Study Completion (Estimated): September 5, 2024

Study Registration Dates

• First Submitted: September 19, 2018
• First Submitted That Met QC Criteria: October 10, 2018
• First Posted (Actual): October 11, 2018

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Lung Cancer; Carcinoma; Small Cell Lung Cancer; SCLC; LS-SCLC; Limited Stage
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab; Tremelimumab
• Other Study ID Numbers: D933QC00001; 2018-000867-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No