Clinical trial NCT02711553: A Study of Ramucirumab (LY3009806) or Merestinib (LY2801653) in Advanced or Metastatic Biliary Tract Cancer
Official 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Biliary Tract Cancer
Metastatic Cancer
Advanced Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2016-03-17
Enrollment: 309
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

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.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Randomization to Progressive Disease or Death from Any Cause (Up To 20 Months)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Randomization to Date of Death from Any Cause (Up To 48 Months)
measure: Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)
timeFrame: Randomization to Disease Progression (Up To 30 Months)
measure: Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)
timeFrame: Randomization to Disease Progression (Up To 30 Months)
measure: Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab
timeFrame: C1 D8, C2 D1, C3 D1, C4 D1,C5 D1,C7 D1, C9 D1 and C13 D1: Within 3 days Prior to Infusion(PTI)
measure: PK: Plasma Concentration of Merestinib
timeFrame: C1 D8; C2 D1; C4 D1; C6 D1; C8 D1; C2 D8; C4 D8; C6 D8; C8 D8: Morning
measure: Number of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies
timeFrame: Predose Cycle 1 Day 1 through Follow Up (Up To 48 Months)
measure: Change From Baseline in Functional Assessment of Cancer Therapy Hepatobiliary Questionnaire (FACT-Hep)
timeFrame: Baseline, Follow Up (Up To 48 Months)
measure: Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score
timeFrame: Baseline, Follow Up (Up To 48 Months)
measure: Change From Baseline in Participant-Reported EQ-5D-5L Visual Analog Scale (VAS) Score
timeFrame: Baseline, Follow Up (Up To 48 Months)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: The University of Arizona Cancer Center
state: Arizona
city: San Francisco
country: United States
facility: UCSF Medical Center at Mission Bay
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida School of Medicine
state: Florida
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Creve Coeur
country: United States
facility: Washington University Medical School
state: Missouri
city: Saint Louis
country: United States
facility: Washington University Medical School
state: Missouri
city: Saint Louis
country: United States
facility: Washington University Medical School
state: Missouri
city: Saint Peters
country: United States
facility: Washington University Medical School
state: Missouri
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Florida Cancer Specialists
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
city: Caba
country: Argentina
facility: Alexander Fleming
state: BS
city: Capital Federal
country: Argentina
facility: Hospital de Gastroenterologia Udaondo
state: Buenos Aires
city: San Salvador de Jujuy
country: Argentina
facility: Fundacion Ars Medica
state: Jujuy
city: Viedma
country: Argentina
facility: Clinica Viedma
state: Río Negro
city: San Miguel de Tucumán
country: Argentina
facility: Centro Medico San Roque
state: Tucumán
city: Ciudad de Buenos Aires
country: Argentina
facility: Fundacion Favaloro
city: La Rioja
country: Argentina
facility: Fundación CORI para la Investigación y Prevención del Cáncer
city: San Juan
country: Argentina
facility: Centro Polivalente de Asistencia e Inv. Clinica CER-San Juan
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Wiener Neustadt
country: Austria
facility: Landesklinikum Wr. Neustadt
state: Niederösterreich
city: Salzburg
country: Austria
facility: Universitätsklinikum Salzburg
city: Wien
country: Austria
facility: KH der Barmherzigen Brüder Wien
city: Bruxelles
country: Belgium
facility: Cliniques universitaires Saint-Luc
state: Brussel
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
city: Brno
country: Czechia
facility: Masarykuv onkologicky ustav
state: Brno-město
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Praha 5
country: Czechia
facility: Fakultni Nemocnice v Motole
city: Aarhus C
country: Denmark
facility: Aarhus Universitetshospital, Aarhus Sygehus
city: Odense C
country: Denmark
facility: Odense Universitetshospital
city: Bordeaux
country: France
facility: CHU de Bordeaux Hop St ANDRE
state: Gironde
city: Lyon
country: France
facility: Centre Leon Berard
state: Rhône-Alpes
city: Besancon Cedex
country: France
facility: CHU de Besancon Hopital Jean Minjoz
city: Lille
country: France
facility: Hôpital C. HURIEZ
city: Montpellier Cedex 5
country: France
facility: CHRU de Montpellier-Hopital St Eloi
city: Nice
country: France
facility: Centre Antoine-Lacassagne
city: Villejuif Cedex
country: France
facility: Gustave Roussy
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
state: Baden-Württemberg
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
state: Baden-Württemberg
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
state: Bayern
city: Hannover
country: Germany
facility: Medizinische Hochschule Hanover
state: Niedersachsen
city: Berlin
country: Germany
facility: HELIOS Klinikum Berlin-Buch
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont Onkologiai Tanszek
state: Hajdu-Bihar
city: Budapest
country: Hungary
facility: Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Korea
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul, Korea
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Mexico
country: Mexico
facility: Arke Estudios Clinicos S.A. de C.V.
state: DF
city: San Luis Potosi
country: Mexico
facility: Centro de Alta Especialidad Reumatologia Inv del Potosi SC
city: St. Petersburg
country: Russian Federation
facility: Russian Scientific Center of Radiology and Surgical Technologies
state: Sankt-Peterburg
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Clinical Oncological Dispensary
city: Moscow
country: Russian Federation
facility: Blokhin Cancer Research Center
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Petersburg City Clinical Oncology Dispensary
city: Hospitalet De Llobregat
country: Spain
facility: Hospital Duran I Reynals
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Clinico de San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malmö
country: Sweden
facility: Skåne universitetssjukhus
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset i Solna
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital - Kaohsiung Branch
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng-Kung Uni. Hosp.
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan City
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou
city: Adana
country: Turkey
facility: Baskent University Dr. Turgut Noyan Research and Training Center
city: Ankara
country: Turkey
facility: Hacettepe University Faculty of Medicine
city: Antalya
country: Turkey
facility: Akdeniz University Medical Faculty
city: Edirne
country: Turkey
facility: Trakya University
city: Istanbul
country: Turkey
facility: Istanbul Universitesi-Cerrahpasa Cerrahpasa Tip Fakultesi Yerleskesi
city: London
country: United Kingdom
facility: University College Hospital - London
state: Greater London
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: Greater Manchester
city: Acton
country: United Kingdom
facility: Hammersmith Hospital
state: London
city: Bebbington
country: United Kingdom
facility: The Clatterbridge Cancer Centre
state: Merseyside
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
state: Surrey
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: Valle JW, Vogel A, Denlinger CS, He AR, Bai LY, Orlova R, Van Cutsem E, Adeva J, Chen LT, Obermannova R, Ettrich TJ, Chen JS, Wasan H, Girvan AC, Zhang W, Liu J, Tang C, Ebert PJ, Aggarwal A, McNeely SC, Moser BA, Oliveira JM, Carlesi R, Walgren RA, Oh DY. Addition of ramucirumab or merestinib to standard first-line chemotherapy for locally advanced or metastatic biliary tract cancer: a randomised, double-blind, multicentre, phase 2 study. Lancet Oncol. 2021 Oct;22(10):1468-1482. doi: 10.1016/S1470-2045(21)00409-5.