Phase III Study of Docetaxel + Ramucirumab or Placebo in Breast Cancer
November 3, 2021 updated by: Eli Lilly and Company
A Multicenter, Multinational, Randomized, Double-Blind, Phase III Study of IMC-1121B Plus Docetaxel Versus Placebo Plus Docetaxel in Previously Untreated Patients With HER2-Negative, Unresectable, Locally-Recurrent or Metastatic Breast Cancer
The objective of this study is to compare the progression-free survival (PFS) of the drug combination ramucirumab plus docetaxel to placebo plus docetaxel in previously untreated participants with human epidermal growth factor receptor 2 (HER2)-negative, unresectable, locally-recurrent or metastatic breast cancer.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Female participants at least 18 years of age with histologically or cytologically confirmed, human epidermal growth factor receptor 2 (HER2) negative breast adenocarcinoma that is metastatic or locally-recurrent and inoperable with curative intent will be randomized. Participants may not have received chemotherapy for metastatic or locally-recurrent, inoperable breast cancer.
It is anticipated that 1113 participants will be randomized with 371 participants in the docetaxel plus placebo arm and 742 participants in the docetaxel plus ramucirumab (IMC-1121B) arm. There will be approximately 250 centers in North and South America, Europe, Asia, Middle East, Africa, Australia, and New Zealand.
On Day 1 of each 21-day cycle, participants will receive docetaxel 75 mg/m² as a one-hour I.V. infusion followed by either ramucirumab (IMC-1121B) 10 mg/kg or placebo 10 mg/kg as a one-hour I.V. infusion. Each cycle is repeated every 21 days.
Treatment will continue until there is evidence of progressive disease, unacceptable toxicity, or other withdrawal criteria are met. Participants who discontinue study treatment with either ramucirumab (IMC-1121B) or placebo may continue to receive docetaxel.
Study Type
Interventional
Enrollment (Actual)
1144
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Bankstown, Australia, NSW2200
- ImClone Investigational Site
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Bedford Park, Australia, SA 5042
- ImClone Investigational Site
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Box Hill, Australia, V1C 3128
- ImClone Investigational Site
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Darlinghurst, Australia, NSW 2010
- ImClone Investigational Site
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East Bentleigh, Australia, VIC 3165
- ImClone Investigational Site
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East Melbourne, Australia, 3002
- ImClone Investigational Site
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Herston, Australia, QLD 4029
- ImClone Investigational Site
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Hobart, Australia, 7000
- ImClone Investigational Site
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Milton, Australia, QLD 4064
- ImClone Investigational Site
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Nambour, Australia, QLD 4560
- ImClone Investigational Site
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New Lambton Heights, Australia, NSW 2305
- ImClone Investigational Site
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Perth, Australia, WA 6001
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Ringwood East, Australia, 3135
- ImClone Investigational Site
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Subiaco, Australia, 6008
- ImClone Investigational Site
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Sydney, Australia, NSW 2010
- ImClone Investigational Site
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Tweed Heads, Australia, NSW 2305
- ImClone Investigational Site
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Wendouree, Australia, VIC 3355
- ImClone Investigational Site
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Victoria
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Fitzroy, Victoria, Australia, 3065
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Frankston, Victoria, Australia, 3199
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Brasschaat, Belgium, 2930
- ImClone Investigational Site
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Charleroi, Belgium, 6000
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Edegem, Belgium, 2650
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Gent, Belgium, 9000
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Kortrijk, Belgium, 8500
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Liege, Belgium, 4000
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Namur, Belgium, 5000
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Yvoir, Belgium, 5530
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Ijui, Brazil, 98700-000
- ImClone Investigational Site
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Porto Alegre, Brazil, 90035-001
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Porto Alegre, Brazil, 90430-090
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Porto Alegre, Brazil, 906-000
- ImClone Investigational Site
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Rio de Janeiro, Brazil, 21941-913
- ImClone Investigational Site
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San Paulo, Brazil, 05651-901
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San Paulo, Brazil, 1246-000
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Santo Andre, Brazil, 09060-650
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Sao Paulo, Brazil, 01318-000
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Sao Paulo, Brazil, 05651-901
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Sao Paulo, Brazil, 08270-070
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Quebec, Canada, G1S 4L8
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Alberta
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Calgary, Alberta, Canada, T2N4N2
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Edmonton, Alberta, Canada, T6G 1Z2
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British Columbia
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Vancouver, British Columbia, Canada, V5Z 4E6
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Ontario
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Toronto, Ontario, Canada, M4N 3M5
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Weston, Ontario, Canada, M9N 1N8
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Quebec
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Greenfield Park, Quebec, Canada
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Osijek, Croatia, 3100
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Brno, Czechia, 62500
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Kutna Hora, Czechia, 28401
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Pardubice, Czechia, 532 03
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Prague, Czechia, 14059
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Prague, Czechia, 180 80
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Videnska, Czechia, 14059
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Motol
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Praha, Motol, Czechia, 150 06
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Alexandria, Egypt, 21526
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Cairo, Egypt, 11796
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Cairo, Egypt, 16114
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Chemnitz, Germany, 9116
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Hamburg, Germany, 20246
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Hamburg, Germany, 22081
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Kiel, Germany, 24105
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Lubeck, Germany, 23538
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Munchen, Germany, 81675
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Munich, Germany, 80637
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Oldenburg, Germany, 26133
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Saarbrucken, Germany, 66113
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Trier, Germany, 54290
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Tubingen, Germany, 72076
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Cork, Ireland
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Dublin, Ireland, 7
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Dublin, Ireland
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Erlangen, Ireland
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Limerick, Ireland
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Beersheva, Israel, 84101
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Jerusalem, Israel, 91129
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Petach-Tikva, Israel, 49100
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Rehovot, Israel, 76100
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Tel Aviv, Israel, 64239
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Incheon, Korea, Republic of, 400-711
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Seoul, Korea, Republic of, 110-744
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Seoul, Korea, Republic of, 120-752
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Seoul, Korea, Republic of, 135-710
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Beirut, Lebanon
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Bsalim, Lebanon
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Metn, Lebanon
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Saïda, Lebanon
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Zgharta, Lebanon
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Auckland, New Zealand, 1023
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Auckland, New Zealand
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Palmerston North, New Zealand, 4414
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Arequipa, Peru, 054
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Lima, Peru, Lima1
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Lima, Peru, Lima27
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Lima, Peru, Lima34
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Lima, Peru, Lima41
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Lima, Peru, Lime27
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Bytom, Poland, 41-902
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Olsztyn, Poland, 10-228
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Olsztyn, Poland, 10-513
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Engels, Russian Federation, 413115
- ImClone Investigational Site
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Kazan, Russian Federation, 420029
- ImClone Investigational Site
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Kursk, Russian Federation, 305035
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Leningrad Region, Russian Federation
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Lipetsk, Russian Federation, 398005
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Magnitogorsk, Russian Federation, 455001
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Moscow, Russian Federation, 111033
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Moscow, Russian Federation, 115478
- ImClone Investigational Site
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Moscow, Russian Federation, 143423
- ImClone Investigational Site
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Novosibirsk, Russian Federation, 630090
- ImClone Investigational Site
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Omsk, Russian Federation, 644013
- ImClone Investigational Site
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Orenburg, Russian Federation, 460021
- ImClone Investigational Site
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Perm, Russian Federation, 614066
- ImClone Investigational Site
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Samara, Russian Federation, 443031
- ImClone Investigational Site
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Saratov, Russian Federation, 410004
- ImClone Investigational Site
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St. Petersburg, Russian Federation, 197022
- ImClone Investigational Site
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St. Petersburg, Russian Federation, 197758
- ImClone Investigational Site
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Tambov, Russian Federation, 392013
- ImClone Investigational Site
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Ufa, Russian Federation, 450054
- ImClone Investigational Site
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Kragujevac, Serbia, 34000
- ImClone Investigational Site
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Nis, Serbia, 18000
- ImClone Investigational Site
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Sremska Kamenica, Serbia, 21204
- ImClone Investigational Site
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Bratislava, Slovakia, 81250
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Trnava, Slovakia, 91775
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Zilina, Slovakia
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Amanzimtoti, South Africa, 4126
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Bloemfontein, South Africa, 9301
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Durban, South Africa, 4001
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Durban, South Africa, 4091
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Lynnwood, South Africa, 0081
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Port Elizabeth, South Africa, 6045
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Pretoria, South Africa, 0001
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Pretoria, South Africa, 0081
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Pretoria, South Africa, 0181
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Sandton, South Africa, 2199
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Johannesburg
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Parktown, Johannesburg, South Africa, 2193
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Alicante, Spain, 03010
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Badalona, Spain, 08916
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Barbastro, Spain, 22300
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Barcelona, Spain, 08003
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Barcelona, Spain, 08036
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Girona, Spain, 17007
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Jaen, Spain, 23007
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La Coruna, Spain, 15009
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La Laguna - Tenerife, Spain, 38205
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Lleida, Spain, 25198
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Madrid, Spain, 28007
- ImClone Investigational Site
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Madrid, Spain, 28033
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Madrid, Spain, 28034
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Madrid, Spain, 28040
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Madrid, Spain, 28222
- ImClone Investigational Site
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Malaga, Spain, 29010
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Palma de Mallorca, Spain, 07010
- ImClone Investigational Site
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Salamanca, Spain, 37007
- ImClone Investigational Site
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San Sebastian, Spain, 20014
- ImClone Investigational Site
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Santander, Spain, 39008
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Sevilla, Spain, 41013
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Toledo, Spain, 45004
- ImClone Investigational Site
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Valencia, Spain, 46009
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Valencia, Spain
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Zaragoza, Spain, 50009
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Changhua, Taiwan, M20 4BX
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Taipei, Taiwan
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Taoyuan County, Taiwan, 33305
- ImClone Investigational Site
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Bournemouth, United Kingdom, BH7 7DW
- ImClone Investigational Site
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Edinburgh, United Kingdom, EH4 2XU
- ImClone Investigational Site
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Huddersfield, United Kingdom, HD3 3EA
- ImClone Investigational Site
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Hull, United Kingdom, HU16 5JQ
- ImClone Investigational Site
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Manchester, United Kingdom, M20 4BX
- ImClone Investigational Site
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Nottingham, United Kingdom, NG5 1PB
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Alabama
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Birmingham, Alabama, United States, 35202
- ImClone Investigational Site
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Mobile, Alabama, United States, 36608
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Arizona
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Chandler, Arizona, United States, 85224
- ImClone Investigational Site
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Gilbert, Arizona, United States, 85297
- ImClone Investigational Site
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Mesa, Arizona, United States, 85206
- ImClone Investigational Site
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California
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Alhambra, California, United States, 91801
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Bakersfield, California, United States, 93309
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Chula Vista, California, United States, 91911
- ImClone Investigational Site
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La Mesa, California, United States, 91942
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Los Angeles, California, United States, 90095
- ImClone Investigational Site
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Oceanside, California, United States, 92056
- ImClone Investigational Site
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Pasadena, California, United States, 01107
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Pasadena, California, United States, 91105
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San Diego, California, United States, 92123
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Santa Barbara, California, United States, 93105
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Santa Maria, California, United States, 93454
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Santa Monica, California, United States, 90404
- ImClone Investigational Site
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Solvang, California, United States, 93463
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Valencia, California, United States, 91355
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Colorado
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Aurora, Colorado, United States, 80045
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Florida
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Fort Lauderdale, Florida, United States, 33308
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Gainesville, Florida, United States, 32605
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New Port Richey, Florida, United States, 34655
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Georgia
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Atlanta, Georgia, United States, 30341
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Atlanta, Georgia, United States, 30342
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Macon, Georgia, United States, 31217
- ImClone Investigational Site
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Marietta, Georgia, United States, 30060
- ImClone Investigational Site
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Illinois
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Alton, Illinois, United States, 62002
- ImClone Investigational Site
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Chicago, Illinois, United States, 60076
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Chicago, Illinois, United States, 60611
- ImClone Investigational Site
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Skokie, Illinois, United States, 60076
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Indiana
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Elkhart, Indiana, United States, 46514
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Mishawaka, Indiana, United States, 46545
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South Bend, Indiana, United States, 46601
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Westville, Indiana, United States, 46891
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Kentucky
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Lexington, Kentucky, United States, 40604
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Michigan
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Lansing, Michigan, United States, 48912
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Saint Joseph, Michigan, United States, 49085
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Minnesota
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Minneapolis, Minnesota, United States, 55415
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Mississippi
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Southaven, Mississippi, United States, 38671
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Missouri
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Saint Louis, Missouri, United States, 63136
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Nebraska
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Grand Island, Nebraska, United States, 68803
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Kearney, Nebraska, United States, 68845
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Nevada
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Henderson, Nevada, United States, 89052
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New York
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New York, New York, United States, 10011
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North Carolina
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Charlotte, North Carolina, United States, 15830
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Charlotte, North Carolina, United States, 28203
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Charlotte, North Carolina, United States, 28210
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Charlotte, North Carolina, United States, 28211
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Charlotte, North Carolina, United States, 28262
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Charlotte, North Carolina, United States, 28294
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North Dakota
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Bismarck, North Dakota, United States, 58501
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Oklahoma
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Oklahoma City, Oklahoma, United States, 73120
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Oregon
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Portland, Oregon, United States, 97239
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Pennsylvania
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West Reading, Pennsylvania, United States, 19611
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Tennessee
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Bartlett, Tennessee, United States, 38133
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Germantown, Tennessee, United States, 38138
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Memphis, Tennessee, United States, 38104
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Memphis, Tennessee, United States, 38119
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Memphis, Tennessee, United States, 38120
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Niles, Tennessee, United States, 49120
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Oxford, Tennessee, United States, 38655
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Texas
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Lubbock, Texas, United States, 79410
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Temple, Texas, United States, 76508
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Utah
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Salt Lake City, Utah, United States, 84106
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
Inclusion Criteria:
- Participant is able to provide signed informed consent
- Participant is female and ≥ 18 years of age or older if required by local laws or regulations
- Participant has histologically or cytologically confirmed adenocarcinoma of the breast that is now metastatic or locally-recurrent and inoperable with curative intent. Every effort should be made to make paraffin-embedded tissue or slides from the diagnostic biopsy or surgical specimen available for confirmation of diagnosis
- Participant has measurable and/or non-measurable disease
- Participants' primary and/or metastatic tumor is human epidermal growth factor receptor 2 (HER2)-negative by fluorescence in-situ hybridization (FISH) or chromogenic in-situ hybridization (CISH) or 0, 1+ overexpression by immunohistochemistry (IHC)
- Participant has not received prior chemotherapy for metastatic or locally-recurrent and inoperable breast cancer
- Participant completed (neo) adjuvant taxane therapy at least 6 months prior to randomization
- Participant completed (neo) adjuvant biologic therapy at least 6 weeks prior to randomization
- Participant completed all prior radiotherapy with curative intent ≥ 3 weeks prior to randomization
- Participant may have received prior hormonal therapy for breast cancer in the (neo) adjuvant and/or the metastatic setting ≥ 2 weeks prior to randomization
- Participant's left ventricular ejection fraction is within normal institutional ranges
- Participant has resolution to grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3 (NCI-CTCAE v 3.0) of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy with the exception of peripheral neuropathy which must have resolved to grade ≤ 2
- Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Participant is amenable to compliance with protocol schedules and testing
- Participant has adequate hematological functions [absolute neutrophil count (ANC) ≥ 1500 cells/microliter (mcL), hemoglobin ≥ 9 grams/deciliter (g/dL), and platelets ≥ 100,000 cells/mcL and ≤ 850,000 cells/mcL]
- Participant has adequate hepatic function [bilirubin within normal limits (WNL), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 times the upper limit of normal (ULN), or ≤ 5.0 times the ULN if the transaminase elevation is due to liver metastases, and alkaline phosphatase ≤ 5.0 times the ULN]
- Participant has serum creatinine ≤ 1.5 x ULN. If serum creatinine > 1.5 x ULN the calculated creatinine clearance should be > 40 milliliters/minute (mL/min)
- Participant's urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA); if urine protein ≥ 2+, a 24-hour urine collection must demonstrate < 1000 milligrams (mg) of protein in 24 hours to allow participation in the study
- Participant must have adequate coagulation function as defined by international normalized ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 1.5 X ULN if not receiving anticoagulation therapy. Participants on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight heparin and if on warfarin must have a INR between 2 and 3 and have no active bleeding (defined as within 14 days of randomization) or pathological condition that carries a high risk of bleeding (such as, tumor involving major vessels or known varices)
- Women of childbearing potential must implement adequate contraception in the opinion of the investigator
- Participant has not received prior biologic therapy for metastatic or locally recurrent and inoperable breast cancer
Exclusion Criteria:
- Participant has a concurrent active malignancy other than breast adenocarcinoma, adequately treated non melanomatous skin cancer, or other non-invasive carcinoma or in situ neoplasm. A participant with previous history of malignancy is eligible, provided that she has been disease free for > 3 years
- Participant has a known sensitivity to docetaxel or other drugs formulated with polysorbate 80
- Participant has a known sensitivity to agents of similar biologic composition as ramucirumab or other agents that specifically target vascular endothelial growth factor (VEGF)
- Participant has a history of chronic diarrheal disease within 6 months prior to randomization
- Participant has received irradiation to a major bone marrow area as defined as > 25% of bone marrow (such as, pelvic or abdominal radiation) within 30 days prior to randomization
- Participant has participated in clinical trials of experimental agents within 4 weeks prior to randomization
- Participant has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders
- Participant has active, high risk bleeding (such as, via gastric ulcers or gastric varices) within 14 days prior to randomization
- Participant has an ongoing or active infection requiring parenteral antibiotic, antifungal, or antiviral therapy
- Participant has uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders in the opinion of the investigator
- Participant has brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease
- Participant has known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness
- Participant has pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
- Participant is pregnant or lactating
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: ramucirumab (IMC-1121B) + docetaxel
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Ramucirumab (IMC-1121B) is administered at a dose of 10 milligrams per kilogram (mg/kg) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
Other Names:
Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
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Placebo Comparator: placebo + docetaxel
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Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
Placebo comparator for ramucirumab (IMC-1121B) administered at a dose of 10 mg/kg as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Progression-Free Survival (PFS)
Time Frame: Randomization to disease progression or death or until data cutoff of 31 Mar 2013 (up to 56 months)
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PFS was defined as time from randomization until the first evidence of progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.0) or death from any cause; by Investigator assessment.
Progressive disease (PD) was defined as at least a 20% increase in sum of longest diameter of target lesions taking as reference the smallest sum longest diameter since baseline, progression in non-target lesions or the appearance of 1 or more new lesion(s).
Participants who neither progressed nor died were censored the day of their last radiographic tumor assessment if available or date of randomization if no post initiation radiographic assessment was available.
If death or PD occurred after ≥2 missing radiographic visits, censoring occurred at date of the last radiographic visit prior to the missed visits.
The symptomatic/clinical disease progression (deterioration) without documented radiologic progression did not constitute progression.
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Randomization to disease progression or death or until data cutoff of 31 Mar 2013 (up to 56 months)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Overall Survival (OS)
Time Frame: Randomization to death or until data cutoff of 29-May-2015 (up to 82 months)
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OS was defined as the duration from randomization to death from any cause.
Participants who were alive at data cut-off for the OS analysis or lost to follow-up were censored on the last date the participant was known to be alive.
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Randomization to death or until data cutoff of 29-May-2015 (up to 82 months)
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Time to Progression (TTP)
Time Frame: Randomization to disease progression or until data cutoff of 31-Mar-2013 (up to 56 months)
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TTP was defined as the time from the date of randomization to the first documented date of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria; by Investigator assessment.
Progressive disease (PD) was defined as at least a 20% increase in sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD since baseline, progression in non-target lesions or the appearance of 1 or more new lesion(s).
Participants who did not progress were censored at the last radiographic tumor assessment.
If no post-baseline assessment was available censoring occurred at the date of randomization.
If PD occurred after 2 or more missing radiographic visits, censoring occurred at the date of the last radiographic visit prior to the missed visits.
The symptomatic/clinical disease progression (deterioration) without documented radiologic progression did not constitute progression.
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Randomization to disease progression or until data cutoff of 31-Mar-2013 (up to 56 months)
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Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate)
Time Frame: Randomization to disease progression or until data cutoff of 31-Mar-2013 (up to 56 months)
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Objective response rate (ORR) was defined as the percentage of randomized participants achieving a best confirmed overall response of CR or PR using Response Evaluation Criteria in Solid Tumors (RECIST v1.0), based on the achievement of both measurement and confirmation criteria; by Investigator assessment.
CR was defined as the disappearance of all target and non-target lesions.
PR was defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions, taking as reference the baseline sum LD and no progression in non-target lesions.
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Randomization to disease progression or until data cutoff of 31-Mar-2013 (up to 56 months)
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Duration of Response
Time Frame: Date of first CR or PR to PD or death or until data cutoff date of 31-Mar-2013 (up to 56 months)
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Duration of complete response (CR) or partial response (PR) measured from time criteria were first met for CR or PR until first date of progressive disease (PD) or death from any cause defined using Response Evaluation Criteria in Solid Tumor (RECIST 1.0); by Investigator assessment.
CR defined as disappearance of all target and non-target lesions.
PR defined as ≥30% decrease in sum of longest diameter (LD) of target lesions and no progression in non-target lesions.
PD defined as ≥20% increase in LD sum of target lesions taking as reference the smallest sum LD since baseline, progression in non-target lesions or the appearance of ≥1 new lesion(s).
Participants who did not relapse or die censored at day of last radiographic tumor assessment.
If death or PD was after ≥2 missing radiographic visits, censoring was at date of last radiographic visit prior to missed visits.
Symptomatic/clinical disease progression without documented radiologic progression did not constitute progression.
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Date of first CR or PR to PD or death or until data cutoff date of 31-Mar-2013 (up to 56 months)
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Total Functional Assessment of Cancer Therapy-Breast (FACT-B): Change From Baseline to End of Therapy
Time Frame: Baseline, End of Therapy or until data cutoff of 31-Mar-2013 (up to 56 months)
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FACT-B measures the following domains of health-related quality of life (HR-QoL): physical well-being (PWB), social/family well-being (SFWB), emotional well-being (EWB), functional well-being (FWB), and additional concerns of breast cancer subscale (BCS) each with 6 or more items developed to measure problems specific to breast cancer symptoms plus additional items related to global QoL.
Participants respond to each of the 36 questions on a 5-point scale from 0 (not at all) to 4 (very much) with a total scores range of 0-144.
Higher scores indicate fewer symptoms and better HR-QoL.
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Baseline, End of Therapy or until data cutoff of 31-Mar-2013 (up to 56 months)
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Number of Participants With Adverse Events
Time Frame: First dose to study completion (up to 12.3 years)
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Clinically significant events were defined as serious adverse events (SAE) and other treatment-emergent non-serious adverse events (NSAE).
A summary of SAEs and other NSAEs is located in the Reported Adverse Event module.
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First dose to study completion (up to 12.3 years)
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Immunogenicity: Percentage of Participants With Treatment Emergent Anti-Ramucirumab Antibodies Until Primary Data Cutoff of 31-Mar-2013
Time Frame: Baseline, prior to cycle 3 infusion, prior to cycle 5 infusion, onset of infusion reaction, resolution of reaction and 30 days following the event up to 56 months
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Percentage of participants with treatment-emergent positive for anti-ramucirumab (IMC-1121B) antibodies during the study.
Participants were considered positive for anti-ramucirumab (IMC-1121B) antibodies if they exhibited a post-treatment antibody level that exceeded the positive upper cut point determined from the anti-ramucirumab (IMC-1121B) level seen in healthy untreated individuals.
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Baseline, prior to cycle 3 infusion, prior to cycle 5 infusion, onset of infusion reaction, resolution of reaction and 30 days following the event up to 56 months
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Immunogenicity: Percentage of Participants Available After 31-Mar-2013 With Treatment Emergent Anti-Ramucirumab Antibodies Until Data Cutoff From 01-Apr-2013 to 08-Sep-2016
Time Frame: Follow-up from 01-Apr-2013 to 08-Sep-2016 (Up to 56 -97 months)
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Percentage of participants with treatment-emergent positive for anti-ramucirumab (IMC-1121B) antibodies during the study.
Participants were considered positive for anti-ramucirumab (IMC-1121B) antibodies if they exhibited a post-treatment antibody level that exceeded the positive upper cut point determined from the anti-ramucirumab (IMC-1121B) level seen in healthy untreated individuals.
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Follow-up from 01-Apr-2013 to 08-Sep-2016 (Up to 56 -97 months)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Arnold D, Fuchs CS, Tabernero J, Ohtsu A, Zhu AX, Garon EB, Mackey JR, Paz-Ares L, Baron AD, Okusaka T, Yoshino T, Yoon HH, Das M, Ferry D, Zhang Y, Lin Y, Binder P, Sashegyi A, Chau I. Meta-analysis of individual patient safety data from six randomized, placebo-controlled trials with the antiangiogenic VEGFR2-binding monoclonal antibody ramucirumab. Ann Oncol. 2017 Dec 1;28(12):2932-2942. doi: 10.1093/annonc/mdx514.
- Spera G, Fresco R, Fung H, Dyck JRB, Pituskin E, Paterson I, Mackey JR. Beta blockers and improved progression-free survival in patients with advanced HER2 negative breast cancer: a retrospective analysis of the ROSE/TRIO-012 study. Ann Oncol. 2017 Aug 1;28(8):1836-1841. doi: 10.1093/annonc/mdx264.
- Mackey JR, Ramos-Vazquez M, Lipatov O, McCarthy N, Krasnozhon D, Semiglazov V, Manikhas A, Gelmon KA, Konecny GE, Webster M, Hegg R, Verma S, Gorbunova V, Abi Gerges D, Thireau F, Fung H, Simms L, Buyse M, Ibrahim A, Martin M. Primary results of ROSE/TRIO-12, a randomized placebo-controlled phase III trial evaluating the addition of ramucirumab to first-line docetaxel chemotherapy in metastatic breast cancer. J Clin Oncol. 2015 Jan 10;33(2):141-8. doi: 10.1200/JCO.2014.57.1513. Epub 2014 Sep 2.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 6, 2008
Primary Completion (Actual)
March 31, 2013
Study Completion (Actual)
November 19, 2020
Study Registration Dates
First Submitted
June 20, 2008
First Submitted That Met QC Criteria
June 20, 2008
First Posted (Estimate)
June 23, 2008
Study Record Updates
Last Update Posted (Actual)
December 6, 2021
Last Update Submitted That Met QC Criteria
November 3, 2021
Last Verified
November 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 13892
- 2008-001727-65 (EudraCT Number)
- TRIO-012 (Other Identifier: Cancer International Research Group (CIRG))
- TRIO-CIRG-012 (Other Identifier: Cancer International Research Group (CIRG))
- CP12-0606 (Other Identifier: ImClone Systems)
- I4T-IE-JVBC (Other Identifier: Eli Lilly and Company)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD Plan Description
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
IPD Sharing Time Frame
Data are available 6 months after the primary publication and approval of the indication studied in the US and european union (EU), whichever is later.
Data will be indefinitely available for requesting.
IPD Sharing Access Criteria
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Clinical Study Report (CSR)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.