Breast CancerPhase 3NCT00703326
Phase III Study of Docetaxel + Ramucirumab or Placebo in Breast Cancer
A Phase 3 study testing ramucirumab (IMC-1121B) and docetaxel in people with Breast Cancer, run by Eli Lilly and Company at 232 sites in 23 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- ramucirumab (IMC-1121B) and docetaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,144 participants
- Where
- 232 sitesin 23 countries
- Study dates
- 6 Aug 2008to 19 Nov 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
232 sites in 23 countries.
232 sites in 23 countries
United States65 sites
ImClone Investigational Site
Alhambra, California, 91801
ImClone Investigational Site
Alton, Illinois, 62002
ImClone Investigational Site
Atlanta, Georgia, 30341
ImClone Investigational Site
Atlanta, Georgia, 30342
ImClone Investigational Site
Aurora, Colorado, 80045
ImClone Investigational Site
Bakersfield, California, 93309
ImClone Investigational Site
Bartlett, Tennessee, 38133
ImClone Investigational Site
Birmingham, Alabama, 35202
ImClone Investigational Site
Bismarck, North Dakota, 58501
ImClone Investigational Site
Chandler, Arizona, 85224
ImClone Investigational Site
Charlotte, North Carolina, 15830
ImClone Investigational Site
Charlotte, North Carolina, 28203
ImClone Investigational Site
Charlotte, North Carolina, 28210
ImClone Investigational Site
Charlotte, North Carolina, 28211
ImClone Investigational Site
Charlotte, North Carolina, 28262
ImClone Investigational Site
Charlotte, North Carolina, 28294
ImClone Investigational Site
Chicago, Illinois, 60076
ImClone Investigational Site
Chicago, Illinois, 60611
ImClone Investigational Site
Chula Vista, California, 91911
ImClone Investigational Site
Elkhart, Indiana, 46514
ImClone Investigational Site
Fort Lauderdale, Florida, 33308
ImClone Investigational Site
Gainesville, Florida, 32605
ImClone Investigational Site
Germantown, Tennessee, 38138
ImClone Investigational Site
Gilbert, Arizona, 85297
ImClone Investigational Site
Grand Island, Nebraska, 68803
ImClone Investigational Site
Henderson, Nevada, 89052
ImClone Investigational Site
Kearney, Nebraska, 68845
ImClone Investigational Site
La Mesa, California, 91942
ImClone Investigational Site
Lansing, Michigan, 48912
ImClone Investigational Site
Lexington, Kentucky, 40604
ImClone Investigational Site
Los Angeles, California, 90095
ImClone Investigational Site
Lubbock, Texas, 79410
ImClone Investigational Site
Macon, Georgia, 31217
ImClone Investigational Site
Marietta, Georgia, 30060
ImClone Investigational Site
Memphis, Tennessee, 38104
ImClone Investigational Site
Memphis, Tennessee, 38119
ImClone Investigational Site
Memphis, Tennessee, 38120
ImClone Investigational Site
Mesa, Arizona, 85206
ImClone Investigational Site
Minneapolis, Minnesota, 55415
ImClone Investigational Site
Mishawaka, Indiana, 46545
ImClone Investigational Site
Mobile, Alabama, 36608
ImClone Investigational Site
New Port Richey, Florida, 34655
ImClone Investigational Site
New York, New York, 10011
ImClone Investigational Site
Niles, Tennessee, 49120
ImClone Investigational Site
Oceanside, California, 92056
ImClone Investigational Site
Oklahoma City, Oklahoma, 73120
ImClone Investigational Site
Oxford, Tennessee, 38655
ImClone Investigational Site
Pasadena, California, 01107
ImClone Investigational Site
Pasadena, California, 91105
ImClone Investigational Site
Portland, Oregon, 97239
ImClone Investigational Site
Saint Joseph, Michigan, 49085
ImClone Investigational Site
Salt Lake City, Utah, 84106
ImClone Investigational Site
San Diego, California, 92123
ImClone Investigational Site
Santa Barbara, California, 93105
ImClone Investigational Site
Santa Maria, California, 93454
ImClone Investigational Site
Santa Monica, California, 90404
ImClone Investigational Site
Skokie, Illinois, 60076
ImClone Investigational Site
Solvang, California, 93463
ImClone Investigational Site
South Bend, Indiana, 46601
ImClone Investigational Site
Southaven, Mississippi, 38671
ImClone Investigational Site
St Louis, Missouri, 63136
ImClone Investigational Site
Temple, Texas, 76508
ImClone Investigational Site
Valencia, California, 91355
ImClone Investigational Site
West Reading, Pennsylvania, 19611
ImClone Investigational Site
Westville, Indiana, 46891
Spain25 sites
ImClone Investigational Site
A Coruña, 15009
ImClone Investigational Site
Alicante, 03010
ImClone Investigational Site
Badalona, 08916
ImClone Investigational Site
Barbastro, 22300
ImClone Investigational Site
Barcelona, 08003
ImClone Investigational Site
Barcelona, 08036
ImClone Investigational Site
Donostia / San Sebastian, 20014
ImClone Investigational Site
Girona, 17007
ImClone Investigational Site
Jaén, 23007
ImClone Investigational Site
La Laguna - Tenerife, 38205
ImClone Investigational Site
Lleida, 25198
ImClone Investigational Site
Madrid, 28007
ImClone Investigational Site
Madrid, 28033
ImClone Investigational Site
Madrid, 28034
ImClone Investigational Site
Madrid, 28040
ImClone Investigational Site
Madrid, 28222
ImClone Investigational Site
Málaga, 29010
ImClone Investigational Site
Palma de Mallorca, 07010
ImClone Investigational Site
Salamanca, 37007
ImClone Investigational Site
Santander, 39008
ImClone Investigational Site
Seville, 41013
ImClone Investigational Site
Toledo, 45004
ImClone Investigational Site
Valencia, 46009
ImClone Investigational Site
Valencia
ImClone Investigational Site
Zaragoza, 50009
Australia19 sites
ImClone Investigational Site
Bankstown, NSW2200
ImClone Investigational Site
Bedford Park, SA 5042
ImClone Investigational Site
Box Hill, V1C 3128
ImClone Investigational Site
Darlinghurst, NSW 2010
ImClone Investigational Site
East Bentleigh, VIC 3165
ImClone Investigational Site
East Melbourne, 3002
ImClone Investigational Site
Fitzroy, Victoria, 3065
ImClone Investigational Site
Frankston, Victoria, 3199
ImClone Investigational Site
Herston, QLD 4029
ImClone Investigational Site
Hobart, 7000
ImClone Investigational Site
Milton, QLD 4064
ImClone Investigational Site
Nambour, QLD 4560
ImClone Investigational Site
New Lambton Heights, NSW 2305
ImClone Investigational Site
Perth, WA 6001
ImClone Investigational Site
Ringwood East, 3135
ImClone Investigational Site
Subiaco, 6008
ImClone Investigational Site
Sydney, NSW 2010
ImClone Investigational Site
Tweed Heads, NSW 2305
ImClone Investigational Site
Wendouree, VIC 3355
Russia19 sites
ImClone Investigational Site
Engel's, 413115
ImClone Investigational Site
Kazan', 420029
ImClone Investigational Site
Kursk, 305035
ImClone Investigational Site
Leningrad Region
ImClone Investigational Site
Lipetsk, 398005
ImClone Investigational Site
Magnitogorsk, 455001
ImClone Investigational Site
Moscow, 111033
ImClone Investigational Site
Moscow, 115478
ImClone Investigational Site
Moscow, 143423
ImClone Investigational Site
Novosibirsk, 630090
ImClone Investigational Site
Omsk, 644013
ImClone Investigational Site
Orenburg, 460021
ImClone Investigational Site
Perm, 614066
ImClone Investigational Site
Saint Petersburg, 197022
ImClone Investigational Site
Saint Petersburg, 197758
ImClone Investigational Site
Samara, 443031
ImClone Investigational Site
Saratov, 410004
ImClone Investigational Site
Tambov, 392013
ImClone Investigational Site
Ufa, 450054
Germany11 sites
ImClone Investigational Site
Chemnitz, 9116
ImClone Investigational Site
Hamburg, 20246
ImClone Investigational Site
Hamburg, 22081
ImClone Investigational Site
Kiel, 24105
ImClone Investigational Site
Lübeck, 23538
ImClone Investigational Site
München, 81675
ImClone Investigational Site
Munich, 80637
ImClone Investigational Site
Oldenburg, 26133
ImClone Investigational Site
Saarbrücken, 66113
ImClone Investigational Site
Trier, 54290
ImClone Investigational Site
Tübingen, 72076
South Africa11 sites
ImClone Investigational Site
Bloemfontein, 9301
ImClone Investigational Site
Durban, 4001
ImClone Investigational Site
Durban, 4091
ImClone Investigational Site
eManzimtoti, 4126
ImClone Investigational Site
Lynnwood, 0081
ImClone Investigational Site
Parktown, Johannesburg, 2193
ImClone Investigational Site
Port Elizabeth, 6045
ImClone Investigational Site
Pretoria, 0001
ImClone Investigational Site
Pretoria, 0081
ImClone Investigational Site
Pretoria, 0181
ImClone Investigational Site
Sandton, 2199
Brazil10 sites
ImClone Investigational Site
Ijuí, 98700-000
ImClone Investigational Site
Porto Alegre, 90035-001
ImClone Investigational Site
Porto Alegre, 90430-090
ImClone Investigational Site
Porto Alegre, 906-000
ImClone Investigational Site
Rio de Janeiro, 21941-913
ImClone Investigational Site
Santo André, 09060-650
ImClone Investigational Site
São Paulo, 01318-000
ImClone Investigational Site
São Paulo, 05651-901
ImClone Investigational Site
São Paulo, 08270-070
ImClone Investigational Site
São Paulo, 1246-000
Belgium8 sites
ImClone Investigational Site
Brasschaat, 2930
ImClone Investigational Site
Charleroi, 6000
ImClone Investigational Site
Edegem, 2650
ImClone Investigational Site
Ghent, 9000
ImClone Investigational Site
Kortrijk, 8500
ImClone Investigational Site
Liège, 4000
ImClone Investigational Site
Namur, 5000
ImClone Investigational Site
Yvoir, 5530
Canada7 sites
ImClone Investigational Site
Calgary, Alberta, T2N4N2
ImClone Investigational Site
Edmonton, Alberta, T6G 1Z2
ImClone Investigational Site
Greenfield Park, Quebec
ImClone Investigational Site
Québec, G1S 4L8
ImClone Investigational Site
Toronto, Ontario, M4N 3M5
ImClone Investigational Site
Vancouver, British Columbia, V5Z 4E6
ImClone Investigational Site
Weston, Ontario, M9N 1N8
Czechia7 sites
ImClone Investigational Site
Brno, 62500
ImClone Investigational Site
Kutná Hora, 28401
ImClone Investigational Site
Pardubice, 532 03
ImClone Investigational Site
Prague, Motol, 150 06
ImClone Investigational Site
Prague, 14059
ImClone Investigational Site
Prague, 180 80
ImClone Investigational Site
Videnska, 14059
Peru6 sites
ImClone Investigational Site
Arequipa, 054
ImClone Investigational Site
Lima, Lima1
ImClone Investigational Site
Lima, Lima27
ImClone Investigational Site
Lima, Lima34
ImClone Investigational Site
Lima, Lima41
ImClone Investigational Site
Lima, Lime27
United Kingdom6 sites
ImClone Investigational Site
Bournemouth, BH7 7DW
ImClone Investigational Site
Edinburgh, EH4 2XU
ImClone Investigational Site
Huddersfield, HD3 3EA
ImClone Investigational Site
Hull, HU16 5JQ
ImClone Investigational Site
Manchester, M20 4BX
ImClone Investigational Site
Nottingham, NG5 1PB
Ireland5 sites
ImClone Investigational Site
Cork
ImClone Investigational Site
Dublin, 7
ImClone Investigational Site
Dublin
ImClone Investigational Site
Erlangen
ImClone Investigational Site
Limerick
Israel5 sites
ImClone Investigational Site
Beersheva, 84101
ImClone Investigational Site
Jerusalem, 91129
ImClone Investigational Site
Petah Tikva, 49100
ImClone Investigational Site
Rehovot, 76100
ImClone Investigational Site
Tel Aviv, 64239
Lebanon5 sites
ImClone Investigational Site
Beirut
ImClone Investigational Site
Bsalîm
ImClone Investigational Site
Metn
ImClone Investigational Site
Sidon
ImClone Investigational Site
Zghartā
South Korea4 sites
ImClone Investigational Site
Incheon, 400-711
ImClone Investigational Site
Seoul, 110-744
ImClone Investigational Site
Seoul, 120-752
ImClone Investigational Site
Seoul, 135-710
Egypt3 sites
ImClone Investigational Site
Alexandria, 21526
ImClone Investigational Site
Cairo, 11796
ImClone Investigational Site
Cairo, 16114
New Zealand3 sites
ImClone Investigational Site
Auckland, 1023
ImClone Investigational Site
Auckland
ImClone Investigational Site
Palmerston North, 4414
Poland3 sites
ImClone Investigational Site
Bytom, 41-902
ImClone Investigational Site
Olsztyn, 10-228
ImClone Investigational Site
Olsztyn, 10-513
Serbia3 sites
ImClone Investigational Site
Kamenitz, 21204
ImClone Investigational Site
Kragujevac, 34000
ImClone Investigational Site
Niš, 18000
Slovakia3 sites
ImClone Investigational Site
Bratislava, 81250
ImClone Investigational Site
Trnava, 91775
ImClone Investigational Site
Žilina
Taiwan3 sites
ImClone Investigational Site
Changhua, M20 4BX
ImClone Investigational Site
Taipei
ImClone Investigational Site
Taoyuan County, 33305
About this study
Official title: 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.
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- ramucirumab (IMC-1121B), docetaxel, Placebo
- Keywords
- Metastatic breast cancer, HER2 negative breast cancer, locally recurrent breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ramucirumab (IMC-1121B)Biological
Also called IMC-1121B, LY3009806
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.
docetaxelDrug
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.
PlaceboOther
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.
| Study group | Role | What they receive |
|---|---|---|
| ramucirumab (IMC-1121B) + docetaxel | Experimental | Not described Receives: Biological: ramucirumab (IMC-1121B); Drug: docetaxel |
| placebo + docetaxel | Placebo comparator | Not described Receives: Drug: docetaxel; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS)
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.
Measured: Randomization to disease progression or death or until data cutoff of 31 Mar 2013 (up to 56 months)
Secondary outcomes (8)
Overall Survival (OS)
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.
Measured: Randomization to death or until data cutoff of 29-May-2015 (up to 82 months)
Time to Progression (TTP)
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.
Measured: Randomization to disease progression or until data cutoff of 31-Mar-2013 (up to 56 months)
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate)
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.
Measured: Randomization to disease progression or until data cutoff of 31-Mar-2013 (up to 56 months)
Duration of Response
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.
Measured: Date of first CR or PR to PD or death or until data cutoff date of 31-Mar-2013 (up to 56 months)
Total Functional Assessment of Cancer Therapy-Breast (FACT-B): Change From Baseline to End of Therapy
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.
Measured: Baseline, End of Therapy or until data cutoff of 31-Mar-2013 (up to 56 months)
Number of Participants With Adverse Events
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.
Measured: First dose to study completion (up to 12.3 years)
Immunogenicity: Percentage of Participants With Treatment Emergent Anti-Ramucirumab Antibodies Until Primary Data Cutoff of 31-Mar-2013
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.
Measured: 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
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
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.
Measured: Follow-up from 01-Apr-2013 to 08-Sep-2016 (Up to 56 -97 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2008 (estimated)
- Study start6 Aug 2008
- Primary completion31 Mar 2013
- Study completion19 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 1,144 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00703326
- Sponsor's protocol ID
- 13892
- Other IDs
- 2008-001727-65, TRIO-012, TRIO-CIRG-012, CP12-0606, I4T-IE-JVBC, 2008
- Status last verified
- Nov 2021
- First submitted
- 20 Jun 2008
- Last updated
- 6 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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.
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.
PubMed 28950290Spera 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.
PubMed 28520849Mackey 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.
PubMed 25185099
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00703326
- Acronym / sponsor ID
- 13892
- Conditions
- Breast Cancer
- Keywords
- Metastatic breast cancer, HER2 negative breast cancer, locally recurrent breast cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,144 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- 6 Aug 2008 (actual)
- Primary completion
- 31 Mar 2013 (actual)
- Study completion
- 19 Nov 2020 (actual)
- First posted
- 23 Jun 2008 (estimated)
- Results
- Posted 17 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ramucirumab (IMC-1121B) + docetaxel | Experimental | Biological: ramucirumab (IMC-1121B), Drug: docetaxel |
| placebo + docetaxel | Placebo comparator | Drug: docetaxel, Other: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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)
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ramucirumab (IMC-1121B)Also: IMC-1121B, LY3009806Ramucirumab (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. | Biological | ramucirumab (IMC-1121B) + docetaxel |
| docetaxelDocetaxel 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. | Drug | placebo + docetaxel, ramucirumab (IMC-1121B) + docetaxel |
| PlaceboPlacebo 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. | Other | placebo + docetaxel |
Primary outcome
Progression-Free Survival (PFS)
Time frame: Randomization to disease progression or death or until data cutoff of 31 Mar 2013 (up to 56 months)
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.
8 secondary outcomes
Overall Survival (OS)
Time frame: Randomization to death or until data cutoff of 29-May-2015 (up to 82 months)
Time to Progression (TTP)
Time frame: Randomization to disease progression or until data cutoff of 31-Mar-2013 (up to 56 months)
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)
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)
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)
Number of Participants With Adverse Events
Time frame: First dose to study completion (up to 12.3 years)
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
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28950290Arnold 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.
- Derived from this study: PubMed 28520849Spera 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.
- Derived from this study: PubMed 25185099Mackey 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) study director
Eli Lilly and Company
232 sites in 23 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ramucirumab (IMC-1121B) and docetaxel in people with Breast Cancer, run by Eli Lilly and Company at 232 sites in 23 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 232 sites in United States, Spain, Australia, Russia, Germany and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (PFS) (time frame: Randomization to disease progression or death or until data cutoff of 31 Mar 2013 (up to 56 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00703326, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2021.