Capivasertib+Fulvestrant vs Placebo+Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic HR+/HER2- Breast Cancer (CAPItello-291)

A Phase III Double-blind Randomised Study Assessing the Efficacy and Safety of Capivasertib + Fulvestrant Versus Placebo + Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Breast Cancer Following Recurrence or Progression On or After Treatment With an Aromatase Inhibitor

Phase III, double-blind, randomised study assessing the efficacy of capivasertib + fulvestrant vs placebo + fulvestrant for the treatment of patients with locally advanced (inoperable) or metastatic HR+/HER2- breast cancer following recurrence or progression on or after AI therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Locally Advanced (Inoperable) or Metastatic Breast Cancer
• Intervention / Treatment: Drug: Fulvestrant; Drug: Capivasertib; Drug: Placebo

Detailed Description

Phase III, double-blind, randomised study assessing the efficacy of capivasertib + fulvestrant vs placebo + fulvestrant for the treatment of patients with locally advanced (inoperable) or metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) breast cancer following recurrence or progression on or after aromatase inhibitor (AI) therapy.

• Study Type: Interventional
• Enrollment (Actual): 818
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Berazategui, Argentina, B1884BBF
    • Research Site
  • Buenos Aires, Argentina, C1125ABD
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  • La Rioja, Argentina, 5300
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  • Rosario, Argentina, S2000KZE
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  • Viedma, Argentina, R8500ACE
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• Australia
  • Adelaide, Australia, 5000
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  • Ballarat, Australia, 3350
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  • Birtinya, Australia, 4575
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  • Box Hill, Australia, 3128
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  • Concord, Australia, 2139
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  • Kurralta Park, Australia, 5037
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  • North Sydney, Australia, 2060
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  • Orange, Australia, 2800
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  • Ringwood East, Australia, 3135
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  • South Brisbane, Australia, 4101
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  • Waratah, Australia, 2298
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  • Wendouree, Australia, 3355
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• Belgium
  • Brussels, Belgium, 1090
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  • Brussels, Belgium, 1200
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  • Charleroi, Belgium, 6000
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  • Edegem, Belgium, 2650
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  • Namur, Belgium, 5000
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  • Wilrijk, Belgium, 2610
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• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
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  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
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    • North York, Ontario, Canada, M2K 1E1
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    • Toronto, Ontario, Canada, M4N 3M5
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    • Toronto, Ontario, Canada, M3M 0B2
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• China
  • Baoding, China, 071000
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  • Beijing, China, 100044
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  • Beijing, China, 100191
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  • Changchun, China, 130021
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  • Chongqing, China, 400030
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  • Chongqing, China, 400042
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  • Dalian, China, 116011
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  • Foshan, China, 528000
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  • Gongshu District, China, 310022
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  • Guangzhou, China, 510080
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  • Guangzhou, China, 510095
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  • Hangzhou, China, 310003
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  • Hangzhou, China, 310020
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  • Harbin, China, 150081
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  • Hefei, China, 230001
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  • Hefei, China, 230022
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  • Jinan, China, 250001
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  • Linyi, China, 276001
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  • Nanchang, China, 330009
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  • Nantong, China, 226001
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  • Neijiang, China, 641000
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  • Shanghai, China, 200032
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  • Shanghai, China, 200127
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  • Shantou, China, 515031
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  • Shenyang, China, 110001
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  • Shenyang, China, 110042
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  • Wuhan, China, 430079
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  • Wuhan, China, 430022
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  • Wuhan, China, 430030
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  • Zhengzhou, China, 450008
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• France
  • Besançon, France, 25000
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  • Brest, France, 29609
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  • Metz, France, 57085
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  • Pierre-Bénite, France, 69310
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  • Plerin SUR MER, France, 22190
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  • Pringy, France, 74374
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  • Rouen, France, 76038
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  • Strasbourg, France, 67065
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  • Toulouse, France, 31059
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• Germany
  • Dresden, Germany, 01307
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  • Erlangen, Germany, 91054
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  • Essen, Germany, 45130
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  • Frankfurt, Germany, 60389
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  • Gelsenkirchen, Germany, 45879
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  • Hamburg, Germany, 20246
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  • Hamburg, Germany, 20357
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  • Hamburg, Germany, 20249
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  • Hanover, Germany, 30625
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  • Heidelberg, Germany, 69120
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  • Kiel, Germany, 24105
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  • Mannheim, Germany, 68167
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  • Minden, Germany, 32429
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  • München, Germany, 81377
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  • München, Germany, 80637
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  • Münster, Germany, 48149
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  • Paderborn, Germany, 33161
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  • Potsdam, Germany, 14467
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• Hungary
  • Budapest, Hungary, 1122
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  • Budapest, Hungary, 1134
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  • Debrecen, Hungary, 4032
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  • Kecskemét, Hungary, 6000
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  • Szekszárd, Hungary, 7100
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  • Szolnok, Hungary, 5000
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• Israel
  • Afula, Israel, 1834111
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  • Beersheba, Israel, 84101
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  • Haifa, Israel, 31096
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  • Jerusalem, Israel, 91031
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  • Jerusalem, Israel, 91120
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  • Kfar Saba, Israel, 4428164
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  • Petah Tikva, Israel, 49100
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  • Ramat Gan, Israel, 52621
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• Italy
  • Bergamo, Italy, 24127
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  • Candiolo, Italy, 10060
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  • Catanzaro, Italy, 88100
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  • Livorno, Italy, 57124
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  • Macerata, Italy, 62100
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  • Meldola, Italy, 47014
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  • Milan, Italy, 20141
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  • Modena, Italy, 41124
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  • Naples, Italy, 80131
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  • Prato, Italy, 59100
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  • Roma, Italy, 00128
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• Japan
  • Chiba, Japan, 260-8717
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  • Fukuoka, Japan, 811-1395
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  • Fukushima, Japan, 960-1295
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  • Hidaka-shi, Japan, 350-1298
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  • Hiroshima, Japan, 730-8518
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  • Kagoshima, Japan, 892-0833
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  • Kitaadachi-gun, Japan, 362-0806
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  • Kumamoto, Japan, 860-8556
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  • Kyoto, Japan, 606-8507
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  • Kōtoku, Japan, 135-8550
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  • Matsuyama, Japan, 791-0280
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  • Nagoya, Japan, 464-8681
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  • Nagoya, Japan, 467-8602
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  • Osaka, Japan, 540-0006
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  • Osaka, Japan, 541-8567
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  • Ota-shi, Japan, 373-8550
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  • Sapporo, Japan, 003-0804
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  • Sapporo, Japan, 060-8638
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  • Shinagawa-ku, Japan, 142-8666
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  • Tsu, Japan, 514-8507
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  • Yokohama, Japan, 241-8515
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• Peru
  • Arequipa, Peru, AREQUIPA01
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  • Lima, Peru, LIMA 41
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• Poland
  • Bydgoszcz, Poland, 85-796
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  • Krakow, Poland, 31-501
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  • Olsztyn, Poland, 10-228
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  • Warsaw, Poland, 02-781
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• Russia
  • Moscow, Russia, 115478
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  • Moscow, Russia, 111123
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  • Saint Petersburg, Russia, 197758
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  • Saint Petersburg, Russia, 198255
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  • Samara, Russia, 443031
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  • Sochi, Russia, 354000
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• South Korea
  • Busan, South Korea, 49241
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  • Daegu, South Korea, 41931
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  • Goyang-si, South Korea, 10408
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  • Incheon, South Korea, 22332
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  • Seongnam-si, South Korea, 13620
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  • Seoul, South Korea, 03722
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  • Seoul, South Korea, 05505
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  • Seoul, South Korea, 135-710
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  • Seoul, South Korea, 8308
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  • Suwon, South Korea, 16499
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  • Suwon, South Korea, 16247
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• Spain
  • A Coruña, Spain, 15009
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  • Barcelona, Spain, 08035
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  • Barcelona, Spain, 8003
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  • Córdoba, Spain, 14004
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  • Hosp de Llobregat(Barcelona), Spain, 08907
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  • Jaén, Spain, 23007
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  • La Laguna (Tenerife), Spain, 38320
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  • Lleida, Spain, 25198
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  • Madrid, Spain, 28034
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  • Madrid, Spain, 28046
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  • Madrid, Spain, 28041
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  • Madrid, Spain, 28040
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  • Madrid, Spain, 28007
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  • Madrid, Spain, 28033
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  • Majadahonda, Spain, 28222
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  • Málaga, Spain, 29010
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  • Pamplona, Spain, 31008
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  • Reus, Spain, 43204
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  • Santiago de Compostela, Spain, 15706
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  • Seville, Spain, 41013
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  • Valencia, Spain, 46010
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  • Valencia, Spain, 46009
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• Taiwan
  • Kaohsiung City, Taiwan, 82445
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  • Taichung, Taiwan, 40447
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  • Tainan, Taiwan, 70403
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  • Tainan, Taiwan, 710
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  • Taipei, Taiwan, 10002
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  • Taipei, Taiwan, 11217
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  • Taipei, Taiwan, 11259
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  • Taoyuan, Taiwan, 333
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• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
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  • Bournemouth, United Kingdom, BH7 7DW
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  • Bristol, United Kingdom, BS2 8ED
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  • Cardiff, United Kingdom, CF14 2TL
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  • Cheltenham, United Kingdom, GL53 7AN
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  • London, United Kingdom, SW3 6JJ
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  • London, United Kingdom, NW3 2QG
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  • Manchester, United Kingdom, M20 4GJ
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  • Sutton, United Kingdom, SM25PT
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• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
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  • California
    • Orange, California, United States, 92868
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    • San Francisco, California, United States, 94143
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    • Whittier, California, United States, 90603
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  • Florida
    • Fort Myers, Florida, United States, 33905
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    • Jacksonville, Florida, United States, 32224
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  • Kansas
    • Westwood, Kansas, United States, 66205
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  • Maryland
    • Baltimore, Maryland, United States, 21201
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  • Massachusetts
    • Boston, Massachusetts, United States, 02111-1520
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  • Minnesota
    • Rochester, Minnesota, United States, 55905
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  • Missouri
    • Kansas City, Missouri, United States, 64132
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    • St Louis, Missouri, United States, 63156
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  • New Jersey
    • Paramus, New Jersey, United States, 07652
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  • New Mexico
    • Farmington, New Mexico, United States, 87401
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  • New York
    • Lake Success, New York, United States, 11042
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    • New York, New York, United States, 10011
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  • North Carolina
    • Greensboro, North Carolina, United States, 27403
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  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
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    • Nashville, Tennessee, United States, 37211
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  • Texas
    • Dallas, Texas, United States, 75246
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  • Virginia
    • Midlothian, Virginia, United States, 23114
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  • Washington
    • Puyallup, Washington, United States, 98373
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Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 126 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with an LHRH agonist. Patients are to have commenced concomitant treatment with LHRH agonist prior to or on Cycle 1, Day 1 and must be willing to continue on it for the duration of the study
2. Histologically confirmed HR+/HER2- breast cancer determined from the most recent tumour sample (primary or metastatic), as per the American Society of Clinical Oncology and College of American Pathologists guideline recommendations. To fulfil the requirement of HR+ disease, a breast cancer must express ER with or without co-expression of progesterone receptor.
3. Metastatic or locally advanced disease with radiological or objective evidence of recurrence or progression (the cancer should have shown progression during or after most recent therapy); locally advanced disease must not be amenable to resection with curative intent (patients who are considered suitable for surgical or ablative techniques following potential down-staging with study treatment are not eligible)
4. ECOG/WHO PS: 0-1

5. Patients are to have received treatment with an AI (aromatase inhibitor) containing regimen (single agent or in combination) and have:

   1. Radiological evidence of breast cancer recurrence or progression while on, or within 12 months of the end of (neo)adjuvant treatment with an AI, OR
   2. Radiological evidence of progression while on prior AI administered as a treatment line for locally advanced or metastatic breast cancer (this does not need to be the most recent therapy)
6. Patients must have measurable disease according to RECIST 1.1 and/or at least 1 lytic or mixed (lytic + sclerotic) bone lesion that can be assessed by CT or MRI; patients with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not eligible
7. FFPE tumour sample from primary/recurrent cancer for central testing

Exclusion Criteria:

1. Symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgement
2. More than 2 lines of endocrine therapy for inoperable locally advanced or metastatic disease
3. More than 1 line of chemotherapy for inoperable locally advanced or metastatic disease. Adjuvant and neoadjuvant chemotherapy are not classed as lines of chemotherapy for advanced breast cancer

4. Prior treatment with any of the following:

   1. AKT, PI3K and mTOR inhibitors
   2. Fulvestrant, and other SERDs
   3. Any other chemotherapy, immunotherapy, immunosuppressant medication (other than corticosteroids) or anticancer agents within 3 weeks prior to study treatment initiation.
   4. Potent inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose of study treatment (3 weeks for St John's wort) or drugs that are sensitive to CYP3A4 inhibition within 1 week prior to study treatment initiation.
5. Radiotherapy with a wide field of radiation up to 4 weeks before study treatment initiation (capivasertib/placebo) and/or radiotherapy with a limited field of radiation for palliation up to 2 weeks before study treatment initiation (capivasertib/placebo)
6. With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment
7. Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids up to 4 weeks before study treatment initiation

8. Any of the following cardiac criteria:

   1. Mean resting QT interval corrected by Fridericia's formula (QTcF) >470 msec obtained from 3 consecutive ECGs
   2. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (eg, complete left bundle branch block, third degree heart block)
   3. Any factors that increase the risk of corrected QT interval (QTc) prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, potential for torsades de pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval
   4. Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association (NYHA) grade ≥2
   5. Uncontrolled hypotension - systolic blood pressure <90 mmHg and/or diastolic blood pressure <50 mmHg
   6. Cardiac ejection fraction outside institutional range of normal or <50% (whichever is higher) as measured by echocardiogram (or multiple-gated acquisition [MUGA] scan if an echocardiogram cannot be performed or is inconclusive)

9. Clinically significant abnormalities of glucose metabolism as defined by any of the following:

   1. Patients with diabetes mellitus type 1 or diabetes mellitus type 2 requiring insulin treatment
   2. HbA1c ≥8.0% (63.9 mmol/mol)
10. Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of fulvestrant or LHRH agonist (if applicable)
11. Currently pregnant (confirmed with positive pregnancy test) or breast-feeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Capivasertib + fulvestrant; Fulvestrant: 2 intramuscular injections of 500 mg given on Day 1 of Weeks 1 and 3 of cycle 1, and then on Day 1, Week 1 of each cycle thereafter. Capivasertib: 400 mg (2 oral tablets) BD given on an intermittent weekly dosing schedule. Dosed on Days 1 to 4 in each week of a 28-day treatment cycle.	Drug: Fulvestrant; Patients will be administered 500 mg (2 injections) on Day 1 of Weeks 1 and 3 of Cycle 1, and then on Day 1, Week 1 of each cycle thereafter; Drug: Capivasertib; 400 mg BD (2 tablets of 200 mg taken twice a day = total daily dose 800 mg) given on an intermittent weekly dosing schedule. Patients will be dosed on Days 1 to 4 in each week of a 28-day treatment cycle
Placebo Comparator: Placebo + fulvestrant; Fulvestrant: 2 intramuscular injections of 500 mg given on Day 1 of Weeks 1 and 3 of cycle 1, and then on Day 1, Week 1 of each cycle thereafter. Placebo: 400 mg (2 oral tablets) BD given on an intermittent weekly dosing schedule. Dosed on Days 1 to 4 in each week of a 28-day treatment cycle.	Drug: Fulvestrant; Patients will be administered 500 mg (2 injections) on Day 1 of Weeks 1 and 3 of Cycle 1, and then on Day 1, Week 1 of each cycle thereafter; Drug: Placebo; Placebo to match 400 mg BD (2 tablets of placebo to match 200 mg taken twice daily = placebo to match total daily dose of 800 mg) given on an intermittent weekly dosing schedule. Patients will be dosed on Days 1 to 4 in each week of a 28-day treatment cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival: Overall Population (Months) in the Global Cohort	Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause, in the global cohort. Participants who discontinue treatment prior to progression should continue to be scanned until progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s).	Assessed every 8 weeks for the first 18 months and every 12 weeks thereafter, from randomization to radiological progression.
Progression Free Survival: Overall Population (Percentage) in the Global Cohort	Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s). Participants who discontinue treatment prior to progression should continue to be scanned until progression. Kaplan-Meier estimate was used.	Assessed every 8 weeks for the first 18 months and every 12 weeks thereafter, from randomization to radiological progression.
Progression Free Survival: Altered Population (Months) in the Global Cohort	Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause.	Assessed every 8 weeks for the first 2 years following objective disease progression or treatment discontinuation and then every 12 weeks.
Progression Free Survival: Altered Population (Percentage) in the Global Cohort	Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause. Kaplan-Meier estimate was used.	Assessed every 8 weeks for the first 2 years following objective disease progression or treatment discontinuation and then every 12 weeks.
Progression Free Survival: Overall Population (Months) in the China Cohort	Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause, in the global cohort. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s). Participants who discontinue treatment prior to progression should continue to be scanned until progression.	Assessed every 8 weeks for the first 18 months and every 12 weeks thereafter, from randomization to radiological progression.
Progression Free Survival: Overall Population (Percentage) in the China Cohort	Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s). Participants who discontinue treatment prior to progression should continue to be scanned until progression. Kaplan-Meier estimate was used.	Assessed every 8 weeks for the first 18 months and every 12 weeks thereafter, from randomization to radiological progression.
Progression Free Survival: Altered Population (Months) in the China Cohort	Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause.	Assessed every 8 weeks for the first 2 years following objective disease progression or treatment discontinuation and then every 12 weeks.
Progression Free Survival: Altered Population (Percentage) in the China Cohort	Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause Kaplan-Meier estimate was used.	Assessed every 8 weeks for the first 2 years following objective disease progression or treatment discontinuation and then every 12 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) in the overall population and in the PIK3CA/AKT1/PTEN-altered subgroup.	Overall Survival (OS) in the overall population and in the PIK3CA/AKT1/PTEN-altered subgroup	The time from date of randomisation to the date of death due to any cause up to 51 months
Investigator assessment of PFS2 in the overall population and in the PIK3CA/AKT1/PTEN-altered subgroup.	PFS2 - time from randomisation to second progression by investigator assessment	The time from the date of randomisation to the date of progression subsequent to the first subsequent therapy, or death due to any cause, whichever occurs earlier, up to approximately 51 months
Response Rate (ORR) in the overall population and in the PIK3CA/AKT1/PTEN-altered subgroup.	percentage of patients with at least one investigator-assessed visit response of complete or partial response (as assessed by the investigator, using RECIST 1.1)	Up to Approximately 51 months
Duration of Response (DoR) in the overall population and in the PIK3CA/AKT1/PTEN-altered subgroup.	time from the date of first documented response until date of documented progression (as assessed by the investigator, using RECIST 1.1) or death in the absence of disease progression	Up to Approximately 51 months
Clinical Benefit Rate (CBR) in the overall population and in the PIK3CA/AKT1/PTEN-altered subgroup.	number of patients with complete or partial response or with stable disease maintained ≥24 weeks after randomisation (as assessed by the investigator, using RECIST 1.1)	Up to Approximately 51 months
ocurrence/frequency of AEs and its relationship to study drugs (safety and tolerability) in the overall population and in the PIK3CA/AKT1/PTEN-altered subgroup	AEs graded according to the National Cancer Institute (NCI CTCAE)	Up to Approximately 51 months
plasma concentration of capivasertib	plasma concentration of capivasertib pre-dose and post-dose (C1h and C4h) in the overall population	Minimum plasma concentration (Cmin), plasma concentration 1 hour post-dose (C1h) and 4 hours post-dose (C4h) during cycles 1 and 2 (each cycle is 28 days)
EORTC QLQ BR23(European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire breast cancer specific module) in the overall population and in the PIK3CA/AKT1/PTEN-altered subgroup where applicable	The self-administered instrument includes 23-items and yields 5 multi-item scores (body image, sexual functioning, arm symptoms, breast symptoms, and systemic therapy side effects). Items are scored on a 4-point verbal rating scale: "Not at All," "A Little," "Quite a Bit," and "Very Much". Scores are transformed to a 0 to 100 scale, where higher scores indicate better unctioning, better HRQoL, or greater level of symptom	Up to Approximately 51 months
The EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items) in the overall population and in the PIK3CA/AKT1/PTEN-altered subgroup where applicable	5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), and global health status/QoL scale, along with 5 individual item symptom scores (appetite loss, dyspnoea, insomnia, constipation, and diarrhoea. The EORTC QLQ-C30 will be scored according to the EORTC QLQ-C30 Scoring Manual (Fayers et al. 2001). Higher scores on the global measure of health status and functional scales indicate better health status/function, but higher scores on symptom scales/scores represent greater symptom severity	Up to Approximately 51 months
Time to definitive deterioration of the ECOG (Eastern Cooperative Oncology Group) performance status in the overall population and in the PIK3CA/AKT1/PTEN-altered subgroup where applicable	Time from randomisation to the earlier of the date of the first definitive deterioration or death due to any cause. Deterioration is defined as a 1-point decrease in ECOG score from baseline, and the deterioration is considered definitive if no improvements in the ECOG performance status are observed at a subsequent time of measurement during the treatment period, or at no further assessments following the time point where the deterioration is observed	Up to approximately 51 months

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• Turner NC, Oliveira M, Howell SJ, Dalenc F, Cortes J, Gomez Moreno HL, Hu X, Jhaveri K, Krivorotko P, Loibl S, Morales Murillo S, Okera M, Park YH, Sohn J, Toi M, Tokunaga E, Yousef S, Zhukova L, de Bruin EC, Grinsted L, Schiavon G, Foxley A, Rugo HS; CAPItello-291 Study Group. Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2023 Jun 1;388(22):2058-2070. doi: 10.1056/NEJMoa2214131.
• Turner NC, Oliveira M, Howell SJ, Dalenc F, Cortes J, Gomez HL, Hu X, Jhaveri K, Krivorotko P, Loibl S, Murillo SM, Park YH, Sohn JH, Toi M, Tokunaga E, Yousef S, Zhukova L, de Bruin E, Grinsted L, Schiavon G, Foxley A, Rugo HS. A plain language summary of the CAPItello-291 study: Capivasertib in hormone receptor-positive advanced breast cancer. Future Oncol. 2024;20(37):2901-2913. doi: 10.1080/14796694.2024.2390791. Epub 2024 Sep 16.
• Oliveira M, Rugo HS, Howell SJ, Dalenc F, Cortes J, Gomez HL, Hu X, Toi M, Jhaveri K, Krivorotko P, Loibl S, Morales Murillo S, Okera M, Nowecki Z, Park YH, Sohn JH, Tokunaga E, Yousef S, Zhukova L, Fulford M, Andrews H, Wadsworth I, D'Cruz C, Turner NC; CAPItello-291 study group. Capivasertib and fulvestrant for patients with hormone receptor-positive, HER2-negative advanced breast cancer (CAPItello-291): patient-reported outcomes from a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2024 Sep;25(9):1231-1244. doi: 10.1016/S1470-2045(24)00373-5.
• Dilawari A, Buturla J, Osgood C, Gao X, Chen W, Ricks TK, Schaefer T, Avasarala S, Reyes Turcu F, Pathak A, Kalavar S, Bhatnagar V, Collazo J, Rahman NA, Mixter B, Tang S, Pazdur R, Kluetz P, Amiri-Kordestani L. US Food and Drug Administration Approval Summary: Capivasertib With Fulvestrant for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced or Metastatic Breast Cancer With PIK3CA/AKT1/PTEN Alterations. J Clin Oncol. 2024 Dec;42(34):4103-4113. doi: 10.1200/JCO.24.00427. Epub 2024 Aug 19.

Helpful Links

• CSP redacted
• SAP redacted
• CSR Synopsis
• CSR Synopsis China Cohort

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2020
• Primary Completion (Actual): May 9, 2023
• Study Completion (Estimated): June 22, 2026

Study Registration Dates

• First Submitted: February 20, 2020
• First Submitted That Met QC Criteria: March 11, 2020
• First Posted (Actual): March 12, 2020

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Locally advanced (inoperable) or Metastatic Breast Cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Fulvestrant; capivasertib
• Other Study ID Numbers: D3615C00001; 2019-003629-78 (EudraCT Number); 2023-505042-25-00 (Registry Identifier: CTIS (EU))

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