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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02711553




Registration number
NCT02711553
Ethics application status
Date submitted
14/03/2016
Date registered
17/03/2016

Titles & IDs
Public title
A Study of Ramucirumab (LY3009806) or Merestinib (LY2801653) in Advanced or Metastatic Biliary Tract Cancer
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
Secondary ID [1] 0 0
I3O-MC-JSBF
Secondary ID [2] 0 0
16329
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Biliary Tract Cancer 0 0
Metastatic Cancer 0 0
Advanced Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)

Intervention/exposure
Study type
Interventional
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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS)
Timepoint [1] 0 0
Randomization to Progressive Disease or Death from Any Cause (Up To 20 Months)
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Randomization to Date of Death from Any Cause (Up To 48 Months)
Secondary outcome [2] 0 0
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)
Timepoint [2] 0 0
Randomization to Disease Progression (Up To 30 Months)
Secondary outcome [3] 0 0
Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)
Timepoint [3] 0 0
Randomization to Disease Progression (Up To 30 Months)
Secondary outcome [4] 0 0
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab
Timepoint [4] 0 0
C1 D8, C2 D1, C3 D1, C4 D1,C5 D1,C7 D1, C9 D1 and C13 D1: Within 3 days Prior to Infusion(PTI)
Secondary outcome [5] 0 0
PK: Plasma Concentration of Merestinib
Timepoint [5] 0 0
C1 D8; C2 D1; C4 D1; C6 D1; C8 D1; C2 D8; C4 D8; C6 D8; C8 D8: Morning
Secondary outcome [6] 0 0
Number of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies
Timepoint [6] 0 0
Predose Cycle 1 Day 1 through Follow Up (Up To 48 Months)
Secondary outcome [7] 0 0
Change From Baseline in Functional Assessment of Cancer Therapy Hepatobiliary Questionnaire (FACT-Hep)
Timepoint [7] 0 0
Baseline, Follow Up (Up To 48 Months)
Secondary outcome [8] 0 0
Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score
Timepoint [8] 0 0
Baseline, Follow Up (Up To 48 Months)
Secondary outcome [9] 0 0
Change From Baseline in Participant-Reported EQ-5D-5L Visual Analog Scale (VAS) Score
Timepoint [9] 0 0
Baseline, Follow Up (Up To 48 Months)

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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/05/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
Accrual to date
Final
309
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
2298 - Waratah
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
Argentina
State/province [9] 0 0
BS
Country [10] 0 0
Argentina
State/province [10] 0 0
Buenos Aires
Country [11] 0 0
Argentina
State/province [11] 0 0
Jujuy
Country [12] 0 0
Argentina
State/province [12] 0 0
Río Negro
Country [13] 0 0
Argentina
State/province [13] 0 0
Tucumán
Country [14] 0 0
Argentina
State/province [14] 0 0
Ciudad de Buenos Aires
Country [15] 0 0
Argentina
State/province [15] 0 0
La Rioja
Country [16] 0 0
Argentina
State/province [16] 0 0
San Juan
Country [17] 0 0
Austria
State/province [17] 0 0
Niederösterreich
Country [18] 0 0
Austria
State/province [18] 0 0
Salzburg
Country [19] 0 0
Austria
State/province [19] 0 0
Wien
Country [20] 0 0
Belgium
State/province [20] 0 0
Brussel
Country [21] 0 0
Belgium
State/province [21] 0 0
Gent
Country [22] 0 0
Belgium
State/province [22] 0 0
Leuven
Country [23] 0 0
Czechia
State/province [23] 0 0
Brno-mesto
Country [24] 0 0
Czechia
State/province [24] 0 0
Hradec Kralove
Country [25] 0 0
Czechia
State/province [25] 0 0
Praha 5
Country [26] 0 0
Denmark
State/province [26] 0 0
Aarhus C
Country [27] 0 0
Denmark
State/province [27] 0 0
Odense C
Country [28] 0 0
France
State/province [28] 0 0
Gironde
Country [29] 0 0
France
State/province [29] 0 0
Rhône-Alpes
Country [30] 0 0
France
State/province [30] 0 0
Besancon Cedex
Country [31] 0 0
France
State/province [31] 0 0
Lille
Country [32] 0 0
France
State/province [32] 0 0
Montpellier Cedex 5
Country [33] 0 0
France
State/province [33] 0 0
Nice
Country [34] 0 0
France
State/province [34] 0 0
Villejuif Cedex
Country [35] 0 0
Germany
State/province [35] 0 0
Baden-Württemberg
Country [36] 0 0
Germany
State/province [36] 0 0
Bayern
Country [37] 0 0
Germany
State/province [37] 0 0
Niedersachsen
Country [38] 0 0
Germany
State/province [38] 0 0
Berlin
Country [39] 0 0
Germany
State/province [39] 0 0
Hamburg
Country [40] 0 0
Hungary
State/province [40] 0 0
Hajdu-Bihar
Country [41] 0 0
Hungary
State/province [41] 0 0
Budapest
Country [42] 0 0
Korea, Republic of
State/province [42] 0 0
Korea
Country [43] 0 0
Korea, Republic of
State/province [43] 0 0
Seoul, Korea
Country [44] 0 0
Korea, Republic of
State/province [44] 0 0
Seoul
Country [45] 0 0
Mexico
State/province [45] 0 0
DF
Country [46] 0 0
Mexico
State/province [46] 0 0
Mexico City
Country [47] 0 0
Mexico
State/province [47] 0 0
San Luis Potosi
Country [48] 0 0
Russian Federation
State/province [48] 0 0
Sankt-Peterburg
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Arkhangelsk
Country [50] 0 0
Russian Federation
State/province [50] 0 0
Moscow
Country [51] 0 0
Russian Federation
State/province [51] 0 0
Saint-Petersburg
Country [52] 0 0
Spain
State/province [52] 0 0
Barcelona
Country [53] 0 0
Spain
State/province [53] 0 0
Madrid
Country [54] 0 0
Sweden
State/province [54] 0 0
Malmö
Country [55] 0 0
Sweden
State/province [55] 0 0
Stockholm
Country [56] 0 0
Taiwan
State/province [56] 0 0
Kaohsiung
Country [57] 0 0
Taiwan
State/province [57] 0 0
Taichung
Country [58] 0 0
Taiwan
State/province [58] 0 0
Tainan
Country [59] 0 0
Taiwan
State/province [59] 0 0
Taipei
Country [60] 0 0
Taiwan
State/province [60] 0 0
Taoyuan City
Country [61] 0 0
Turkey
State/province [61] 0 0
Adana
Country [62] 0 0
Turkey
State/province [62] 0 0
Ankara
Country [63] 0 0
Turkey
State/province [63] 0 0
Antalya
Country [64] 0 0
Turkey
State/province [64] 0 0
Edirne
Country [65] 0 0
Turkey
State/province [65] 0 0
Istanbul
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Greater London
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Greater Manchester
Country [68] 0 0
United Kingdom
State/province [68] 0 0
London
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Merseyside
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
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)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
Data are available 6 months after the primary publication and approval of the indication studied in the US and european union (EU), whichever is later. Data will be indefinitely available for requesting.
Available to whom?
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02711553