Erbitux in Combination With Xeloda and Cisplatin in Advanced Esophago-gastric Cancer
EXPAND
Open-label, Randomized, Controlled, Multicenter Phase III Study Investigating Cetuximab in Combination With Capecitabine (Xeloda, X) and Cisplatin (P) Versus XP Alone as First-line Treatment for Subjects With Advanced Gastric Adenocarcinoma Including Adenocarcinoma of the Gastroesophageal Junction
2 other identifiers
interventional
904
24 countries
127
Brief Summary
The primary objective of this study is to demonstrate that addition of cetuximab to 1st-line treatment with capecitabine (Xeloda, X) and cisplatin (P) \[XP\] chemotherapy regimen has a clinically relevant benefit for subjects with advanced gastric adenocarcinoma including gastroesophageal junction (GEJ) adenocarcinoma, in terms of progression free survival (PFS). Secondary objectives are to assess cetuximab plus XP versus XP alone with respect to overall survival, overall tumor response, quality of life (QoL) and safety.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 gastric-cancer
Started Jun 2008
127 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 13, 2008
CompletedFirst Posted
Study publicly available on registry
May 15, 2008
CompletedStudy Start
First participant enrolled
June 1, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2013
CompletedResults Posted
Study results publicly available
May 16, 2013
CompletedJuly 21, 2014
July 1, 2014
3.8 years
May 13, 2008
March 30, 2013
July 11, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free Survival (PFS) Time: Independent Review Committee (IRC) Assessments
The PFS time is defined as the duration from randomization to either first observation of progressive disease (PD) or occurrence of death due to any cause within 60 days of the last tumor assessment or randomization. Participants without event are censored on the date of last tumor assessment.
Time from randomization to disease progression, death or last tumor assessment, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012)
Secondary Outcomes (5)
Overall Survival (OS)
Time from randomization to death or last day known to be alive, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date, (31 Mar 2012)
Best Overall Response (BOR) Rate: Independent Review Committee (IRC) Assessments
Every 6 weeks until progression, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date, (31 Mar 2012)
Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Baseline, Week 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012)
Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire
Baseline, Week 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012)
Safety - Number of Participants With Adverse Events (AEs)
Time from first dose up to Day 30 after last dose of study treatment, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012)
Study Arms (2)
Cetuximab plus Capecitabine plus Cisplatin
EXPERIMENTALCapecitabine plus Cisplatin
ACTIVE COMPARATORInterventions
Single first dose of cetuximab 400 milligram per square meter (mg/m\^2) will be administered intravenously over 120 minutes followed by weekly intravenous infusion of cetuximab 250 mg/m\^2 over 60 minutes in each 3-week treatment cycle, until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Capecitabine 1000 mg/m\^2 will be administered orally twice daily from evening of Day 1 to morning of Day 15 for every 3-week treatment cycle, until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Cisplatin 80 mg/m\^2 will be administered intravenously with infusion over 1 to 4 hours on Day 1 of each 3-week treatment cycle, until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Eligibility Criteria
You may qualify if:
- Written informed consent before any study-related activities are carried out
- Age greater than or equal to (\>=) 18 years
- Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (Adenocarcinoma of the gastroesophageal junction \[AEG\] Types I-III according to Siewert classification)
- Archived tumor material sample for at least subsequent standardized Epidermal Growth Factor Receptor (EGFR) expression assessment
- Unresectable advanced (M0) or unresectable metastatic (M1) disease
- At least one radiographically documented measurable lesion in a previously non-irradiated area according to response evaluation criteria in solid tumors (RECIST). The primary tumor site is to be considered as a non-measurable lesion only
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Estimated life expectancy greater than (\>) 12 weeks
- Medically accepted contraception (if the risk of conception exists)
- Glomerular filtration rate (GFR) \>= 60 milliliter per minute (mL/min) The GFR is based on the Cockcroft-Gault formula for creatinine clearance
- Aspartate-aminotransferase (ASAT) less than or equal to (=\<) 2.5 \* upper limit of normal (ULN) and alanine-aminotransferase (ALAT) =\< 2.5 \*ULN
- Bilirubin =\< 3 \* ULN
- Absolute neutrophil count (ANC) \>= 1.5 \* 10\^9 per liter
- Platelets \>= 100 \* 10\^9 per liter
- Hemoglobin \>=10 gram per deciliter (g/dL) (without transfusions)
- +1 more criteria
You may not qualify if:
- Prior chemotherapy, however, previous (neo-)adjuvant (radio-) chemotherapy allowed if finished \> 1 year prior to start of study treatment and no more than 300 mg/m\^2 cisplatin has been administered
- Prior treatment with an antibody or molecule targeting EGFR and/or Vascular Endothelial Growth Factor Receptor (VEGFR) related signaling pathways
- Brain metastasis and/or leptomeningeal disease (known or suspected)
- Radiotherapy (except localized radiotherapy for pain relief), major surgery or any investigational drug within 30 days before the start of study treatment
- Concurrent chronic systemic immune or hormone therapy not indicated in this study protocol (except for physiologic replacement)
- Clinically relevant coronary artery disease (New York Heart Association \[NYHA\] functional angina classification III/IV), congestive heart failure (NYHA III/IV), clinically relevant cardiomyopathy, history of myocardial infarction in the 12 months before study Screening, or high risk of uncontrolled arrhythmia
- Active Hepatitis B or C
- Chronic diarrhea or short bowel syndrome
- Presence of any contra-indication to treatment with cetuximab, capecitabine and cisplatin including:
- Known hypersensitivity to capecitabine, fluorouracil, cisplatin, cetuximab or to any of the excipients of these drugs
- Known dihydropyrimidine dehydrogenase (DPD) deficiency
- Hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
- Current treatment with sorivudine or chemically related analogues, such as brivudine
- Symptomatic peripheral neuropathy National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade \>= 2 and/or ototoxicity NCI CTCAE Grade \>= 2, except if due to trauma or mechanical impairment due to tumor mass
- Pregnancy or lactation period
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (130)
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Rosario, Argentina
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Coburg VIC, Australia
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Frankston, VIC, Australia
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Perth, Australia
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Graz, Austria
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Kufstein, Austria
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Steyr, Austria
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Vienna, Austria
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Zams, Austria
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Bonheiden, Belgium
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Brussels, Belgium
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Verviers, Belgium
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Campinas, Brazil
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Ijuí, Brazil
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Jaú, Brazil
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Porto Alegre, Brazil
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Salvador, Brazil
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Santo André, Brazil
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Sâo Paulo, Brazil
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Pleven, Bulgaria
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Plovdiv, Bulgaria
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Rousse, Bulgaria
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Sofia, Bulgaria
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Reñaca, Chile
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Santiago, Chile
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Temuco, Chile
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Valparaíso, Chile
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Beijing, China
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Guangzhou, China
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Hefei, China
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Nanjing, China
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Shanghai, China
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Shenyang, China
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Brno, Czechia
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Hradec Králové, Czechia
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Prague, Czechia
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Besançon, France
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Clermont-Ferrand, France
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La Roche-sur-Yon, France
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Marseille, France
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Paris, France
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Rennes, France
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Berlin, Germany
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Bielefeld, Germany
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Braunschweig, Germany
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Cologne, Germany
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Dresden, Germany
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Essen, Germany
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Esslingen am Neckar, Germany
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Frankfurt, Germany
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Giessen, Germany
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Hamburg, Germany
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Heidelberg, Germany
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Ludwigshafen, Germany
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Mainz, Germany
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München, Germany
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Offenbach, Germany
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Regensburg, Germany
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Schwäbisch Hall, Germany
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Schweinfurt, Germany
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Stuttgart, Germany
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Timisoara, Germany
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Troisdorf, Germany
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Ulm, Germany
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Weiden, Germany
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Weilheim, Germany
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Ioannina, Greece
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Thessaloniki, Greece
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Hong Kong, Hong Kong
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Budapest, Hungary
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Győr, Hungary
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Kaposvár, Hungary
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Tatabánya, Hungary
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Haifa, Israel
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Jerusalem, Israel
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Petach Tiqva, Israel
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Ramat Gan, Israel
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Tel Aviv, Israel
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Ancona, Italy
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Bologna, Italy
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Milan, Italy
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Napoli, Italy
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Roma, Italy
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Rozzano (Milano), Italy
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Chiba, Japan
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Ehime, Japan
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Hokkaido, Japan
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Kōtoku, Japan
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Nagoya, Japan
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Osaka, Japan
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Saitama, Japan
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Shizuoka, Japan
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Tochigi, Japan
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Tokyo, Japan
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Yokohama, Japan
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Gdansk, Poland
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Lublin, Poland
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Opole, Poland
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Wroclaw, Poland
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Sana Maria Da Feira, Portugal
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Baia Mare, Romania
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Bucharest, Romania
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Cluj-Napoca, Romania
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Iași, Romania
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Timișoara, Romania
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Kazan', Russia
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Moscow, Russia
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Obninsk, Russia
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Saint Petersburg, Russia
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Anyang, South Korea
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Daegu, South Korea
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Inchon-si, South Korea
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Seongnam, South Korea
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Seoul, South Korea
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Alicante, Spain
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El Palmar-Murcia, Spain
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Lugo, Spain
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Pamplona, Spain
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Santander, Spain
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Seville, Spain
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Valencia, Spain
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Changhua, Taiwan
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Kaohsiung City, Taiwan
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Kaohsiung County, Taiwan
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Taichung, Taiwan
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Tainan, Taiwan
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Taipei, Taiwan
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Taoyuan District, Taiwan
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Guildford, United Kingdom
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Manchester, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Merck KGaA Communication Center
- Organization
- Merck Serono, a division of Merck KGaA
Study Officials
- PRINCIPAL INVESTIGATOR
Florian Lordick, MD, PhD
University Clinic Leipzig, University Cancer Center Leipzig (UCCL), Leipzig Germany
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 13, 2008
First Posted
May 15, 2008
Study Start
June 1, 2008
Primary Completion
March 1, 2012
Study Completion
February 1, 2013
Last Updated
July 21, 2014
Results First Posted
May 16, 2013
Record last verified: 2014-07