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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02711553
Registration number
NCT02711553
Ethics application status
Date submitted
14/03/2016
Date registered
17/03/2016
Date last updated
28/05/2024
Titles & IDs
Public title
A Study of Ramucirumab (LY3009806) or Merestinib (LY2801653) in Advanced or Metastatic Biliary Tract Cancer
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Scientific title
Randomized, Double-Blind, Phase 2 Study of Ramucirumab or Merestinib or Placebo Plus Cisplatin and Gemcitabine as First-Line Treatment in Patients With Advanced or Metastatic Biliary Tract Cancer
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Secondary ID [1]
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I3O-MC-JSBF
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Secondary ID [2]
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16329
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Biliary Tract Cancer
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Metastatic Cancer
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Advanced Cancer
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Condition category
Condition code
Cancer
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Biliary tree (gall bladder and bile duct)
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Ramucirumab
Treatment: Drugs - Merestinib
Treatment: Drugs - Cisplatin
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Placebo Oral
Treatment: Drugs - Placebo IV
Experimental: 8 mg/kg Ramucirumab + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine - Participants received 8 mg/kg ramucirumab plus 25 mg/square meter (mg/m²) cisplatin and 1000 mg/m² gemcitabine intravenously (IV) on days 1 and 8, every 21 days (1 cycle). Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for ramucirumab therapy).
Placebo Comparator: Placebo IV + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine - Participants received placebo (indistinguishable and equivalent volume to ramucirumab) plus 25 mg/m² cisplatin and 1000 mg/m² gemcitabine IV on days 1 and 8, every 21 days (1 cycle). Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for placebo therapy).
Experimental: 80 mg Merestinib + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine - Participants received 80 mg merestinib orally each day, plus 25 mg/m² cisplatin and 1000 mg/m² gemcitabine IV on Days 1 and 8, every 21 days (1 cycle). Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for merestinib therapy).
Placebo Comparator: Placebo Oral + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine - Participants received placebo (indistinguishable to merestinib) orally each day, plus 25 mg/m² cisplatin and 1000 mg/m² gemcitabine IV on Days 1 and 8, every 21 days. Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for placebo therapy).
Treatment: Drugs: Ramucirumab
Administered IV
Treatment: Drugs: Merestinib
Administered orally
Treatment: Drugs: Cisplatin
Administered IV
Treatment: Drugs: Gemcitabine
Administered IV
Treatment: Drugs: Placebo Oral
Administered orally
Treatment: Drugs: Placebo IV
Administered IV
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Progression Free Survival (PFS)
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Assessment method [1]
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PFS time was measured from the date of randomization until the first radiographic documentation of progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of first dose, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.
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Timepoint [1]
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Randomization to Progressive Disease or Death from Any Cause (Up To 20 Months)
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Secondary outcome [1]
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Overall Survival (OS)
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Assessment method [1]
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OS defined as the time from from randomization to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive.
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Timepoint [1]
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Randomization to Date of Death from Any Cause (Up To 48 Months)
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Secondary outcome [2]
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Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)
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Assessment method [2]
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ORR was the number of participants who achieve a best overall response of CR or PR divided by the total number of participants randomized to the corresponding treatment arm as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR 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), no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
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Timepoint [2]
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Randomization to Disease Progression (Up To 30 Months)
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Secondary outcome [3]
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Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)
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Assessment method [3]
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Disease Control Rate (DCR) was the number of participants who achieve a best overall response of CR, PR, or SD divided by the total number of participants randomized to the corresponding treatment arm as per RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
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Timepoint [3]
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Randomization to Disease Progression (Up To 30 Months)
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Secondary outcome [4]
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Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab
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Assessment method [4]
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PK was determined by the minimum observed plasma concentration (Cmin). 1 Cycle (C) = 21 days (D).
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Timepoint [4]
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C1 D8, C2 D1, C3 D1, C4 D1,C5 D1,C7 D1, C9 D1 and C13 D1: Within 3 days Prior to Infusion(PTI)
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Secondary outcome [5]
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PK: Plasma Concentration of Merestinib
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Assessment method [5]
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PK was presented through graphical overlay comparison versus historic data. No numerical summary of data was intended or produced.
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Timepoint [5]
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C1 D8; C2 D1; C4 D1; C6 D1; C8 D1; C2 D8; C4 D8; C6 D8; C8 D8: Morning
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Secondary outcome [6]
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Number of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies
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Assessment method [6]
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Number of participants with positive treatment emergent anti-ramucirumab antibodies (ADA) was summarized by treatment group.
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Timepoint [6]
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Predose Cycle 1 Day 1 through Follow Up (Up To 48 Months)
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Secondary outcome [7]
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Change From Baseline in Functional Assessment of Cancer Therapy Hepatobiliary Questionnaire (FACT-Hep)
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Assessment method [7]
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FACT-Hep consists of 45 items in five subscales (1) physical well-being (PWB) score rage 0 -28; (2) social well-being (SWB) score range 0-28; (3) emotional well-being (EWB) score range 0-24; (4) functional well-being (FWB) score range 0-28; and (5) the hepatobiliary cancer subscale (HCS) Score range 0-72. The Trial Outcomes Index (TOI) is the sum of the PWB, FWB and Hep subscales with a scores range of 0 to 128. The Total FACT-Hep score was the sum of all questions with a scores range of 0 to 180.Total FACT-G score was the sum of the 27 questions in the PWB, SFWB, EWB and FWB with a scores range of 0 to 108. The FACT-Hep Symptoms Index with 8 key questions and scores range of 0 to 32 from the Hep Subscale. Higher score in sub-score or total score indicates better QOL and better health state. Participants were classified as "Improved" if they had positive change from baseline, "Worsened" if they had negative change from baseline, and "Stable" otherwise.
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Timepoint [7]
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Baseline, Follow Up (Up To 48 Months)
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Secondary outcome [8]
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Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score
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Assessment method [8]
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EQ-5D-5L is a 2-part questionnaire that assesses general health status for 'today'. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using country-specific algorithms, with scores ranging from less than 0 (where zero is a health state equivalent to death; negative values are valued as worse than dead) to 1 (perfect health). Index values were calculated using the US algorithm (-0.109 to 1). A higher score indicates better health state.
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Timepoint [8]
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Baseline, Follow Up (Up To 48 Months)
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Secondary outcome [9]
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Change From Baseline in Participant-Reported EQ-5D-5L Visual Analog Scale (VAS) Score
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Assessment method [9]
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EQ-5D-5L is a 2-part questionnaire that assesses general health status 'today'. The second part is assessed using a VAS on which the patient rates their perceived health state, ranging from 0 millimeter (the worst health you can imagine) to 100 millimeter (the best health you can imagine).
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Timepoint [9]
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Baseline, Follow Up (Up To 48 Months)
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Eligibility
Key inclusion criteria
- Have an Eastern Cooperative Oncology Group performance status of 0 or 1.
- Have a histologically or cytologically confirmed diagnosis of non-resectable,
recurrent, or metastatic biliary tract adenocarcinoma (intrahepatic or extrahepatic
cholangiocarcinoma, gallbladder cancer, or Ampulla of Vater) .
- Have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST).
- Have adequate biliary drainage.
- Have adequate organ function.
- Males and females are sterile, postmenopausal, or compliant with a highly effective
contraceptive method.
- Female participants of childbearing potential must have a negative serum pregnancy
test within 7 days prior to first dose.
- Are willing to provide blood/serum/plasma and tumor tissue samples for research
purposes. Submission of blood/serum/plasma and tumor tissue samples is mandatory for
participation in this study, unless restricted per local regulations.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- Previous systemic therapy for locally advanced or metastatic disease is not allowed.
- Have a history of or have current hepatic encephalopathy of any grade, or ascites of
Grade >1, or cirrhosis with Child-Pugh Stage B or higher.
- Have ongoing or recent (=6 months) hepatorenal syndrome.
- Have had a major surgical procedure or significant traumatic injury including
nonhealing wound, peptic ulcer, or bone fracture =28 days prior to randomization.
- Anticipate having a major surgical procedure during the course of the study.
- Has documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord
compression.
- Within 6 months prior to randomization, have had any arterial thrombotic event,
including myocardial infarction, unstable angina, cerebrovascular accident, or
transient ischemic attack.
- Have an uncontrolled arterial hypertension with systolic blood pressure =150 or
diastolic blood pressure =90 millimeters of mercury (mm Hg) despite standard medical
management.
- Have a previous malignancy within 5 years of study entry or a concurrent malignancy.
- Have a history of gastrointestinal perforation and/or fistulae within 6 months prior
to randomization.
- Have a known allergy or hypersensitivity reaction to any of the treatment components.
- Have a history of uncontrolled hereditary or acquired thrombotic disorder.
- Have uncontrolled metabolic disorders or other nonmalignant organ or systemic diseases
or secondary effects of cancer that induce a high medical risk and/or make assessment
of survival uncertain.
- Have mixed hepatocellular biliary tract cancer histology.
- Have a corrected QT interval >470 milliseconds as calculated by the Fridericia
equation.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Active, not recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
19/05/2016
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
31/12/2025
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Actual
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Sample size
Target
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Accrual to date
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Final
309
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Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
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Recruitment hospital [1]
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Calvary Mater Newcastle - Waratah
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Recruitment hospital [2]
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Royal Adelaide Hospital - Adelaide
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Recruitment hospital [3]
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Austin Health - Heidelberg
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Recruitment postcode(s) [1]
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2298 - Waratah
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Recruitment postcode(s) [2]
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5000 - Adelaide
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Recruitment postcode(s) [3]
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3084 - Heidelberg
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Recruitment outside Australia
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United States of America
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Arizona
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United States of America
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California
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United States of America
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District of Columbia
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United States of America
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Florida
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United States of America
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Michigan
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United States of America
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Missouri
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United States of America
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Pennsylvania
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United States of America
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Tennessee
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Argentina
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BS
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Argentina
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Buenos Aires
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Argentina
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Jujuy
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Argentina
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Río Negro
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Argentina
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Tucumán
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Argentina
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Ciudad de Buenos Aires
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Argentina
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La Rioja
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Argentina
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San Juan
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Austria
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Niederösterreich
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Austria
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Salzburg
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Austria
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Wien
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Belgium
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Brussel
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Belgium
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Gent
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Belgium
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Leuven
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Brno-mesto
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Czechia
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Hradec Kralove
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Czechia
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Praha 5
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Denmark
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Aarhus C
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Denmark
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Odense C
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France
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Gironde
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France
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Rhône-Alpes
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France
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Besancon Cedex
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France
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Lille
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France
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Montpellier Cedex 5
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France
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Nice
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France
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Villejuif Cedex
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Germany
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Baden-Württemberg
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Germany
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Bayern
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Germany
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Niedersachsen
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Germany
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Berlin
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Germany
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Hamburg
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Hungary
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Hajdu-Bihar
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Hungary
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Budapest
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Korea, Republic of
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Korea
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Korea, Republic of
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Seoul, Korea
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Korea, Republic of
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Seoul
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Mexico
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DF
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Mexico
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Mexico City
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Mexico
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San Luis Potosi
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Russian Federation
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Sankt-Peterburg
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Russian Federation
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Arkhangelsk
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Russian Federation
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Moscow
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Russian Federation
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Saint-Petersburg
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Spain
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Barcelona
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Spain
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Madrid
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Sweden
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Malmö
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Sweden
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Stockholm
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Taiwan
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Kaohsiung
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Taiwan
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Taichung
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Taiwan
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Tainan
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Taiwan
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Taipei
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Taiwan
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Taoyuan City
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Turkey
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Adana
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Turkey
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Ankara
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Turkey
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Antalya
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Turkey
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Edirne
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Turkey
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Istanbul
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United Kingdom
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Greater London
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United Kingdom
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Greater Manchester
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London
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United Kingdom
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Merseyside
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United Kingdom
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Surrey
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Eli Lilly and Company
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
The main purpose of this study is to evaluate the efficacy and safety of ramucirumab or
merestinib or placebo plus cisplatin and gemcitabine in participants with advanced or
metastatic biliary tract cancer.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02711553
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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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)
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Address
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Eli Lilly and Company
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Country
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0
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02711553
Download to PDF