A Study of Ramucirumab (LY3009806) or Merestinib (LY2801653) in Advanced or Metastatic Biliary Tract Cancer

NCT02711553 | Active Not Recruiting Phase 2 Results

• 3 other identifiers: 16329I3O-MC-JSBF2015-004699-31
• Study Type: interventional
• Target: 309
• Locations: 17 countries
• Sites: 79

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.

Conditions

Biliary Tract Cancer; Metastatic Cancer; Advanced Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  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.

  Randomization to Progressive Disease or Death from Any Cause (Up To 20 Months)

Secondary Outcomes (9)

• Overall Survival (OS)

  Randomization to Date of Death from Any Cause (Up To 48 Months)

• Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)

  Randomization to Disease Progression (Up To 30 Months)

• Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)

  Randomization to Disease Progression (Up To 30 Months)

• Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab

  C1 D8, C2 D1, C3 D1, C4 D1,C5 D1,C7 D1, C9 D1 and C13 D1: Within 3 days Prior to Infusion(PTI)

• PK: Plasma Concentration of Merestinib

  C1 D8; C2 D1; C4 D1; C6 D1; C8 D1; C2 D8; C4 D8; C6 D8; C8 D8: Morning

Study Arms (4)

8 mg/kg Ramucirumab + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

EXPERIMENTAL

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).

Drug: Ramucirumab; Drug: Cisplatin; Drug: Gemcitabine

Placebo IV + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

PLACEBO COMPARATOR

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).

Drug: Cisplatin; Drug: Gemcitabine; Drug: Placebo IV

80 mg Merestinib + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

EXPERIMENTAL

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).

Drug: Merestinib; Drug: Cisplatin; Drug: Gemcitabine

Placebo Oral + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

PLACEBO COMPARATOR

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).

Drug: Cisplatin; Drug: Gemcitabine; Drug: Placebo Oral

Interventions

Ramucirumab DRUG

Administered IV

Also known as: LY3009806

8 mg/kg Ramucirumab + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

Merestinib DRUG

Administered orally

Also known as: LY2801653

80 mg Merestinib + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

Cisplatin DRUG

Administered IV

8 mg/kg Ramucirumab + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine; 80 mg Merestinib + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine; Placebo IV + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine; Placebo Oral + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

Gemcitabine DRUG

Administered IV

Also known as: LY188011

8 mg/kg Ramucirumab + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine; 80 mg Merestinib + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine; Placebo IV + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine; Placebo Oral + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

Placebo Oral DRUG

Administered orally

Placebo Oral + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

Placebo IV DRUG

Administered IV

Placebo IV + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (82)

The University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

UCSF Medical Center at Mission Bay

San Francisco, California, 94158, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

University of Florida School of Medicine

Gainesville, Florida, 32608, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University Medical School

City of Saint Peters, Missouri, 63376, United States

Location

Washington University Medical School

Creve Coeur, Missouri, 63141, United States

Location

Washington University Medical School

St Louis, Missouri, 63110, United States

Location

Washington University Medical School

St Louis, Missouri, 63129, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111-2497, United States

Location

Florida Cancer Specialists

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

Alexander Fleming

CABA, BS, 1426, Argentina

Location

Hospital de Gastroenterologia Udaondo

Capital Federal, Buenos Aires, C1264AAA, Argentina

Location

Fundacion Ars Medica

San Salvador de Jujuy, Jujuy Province, Y4600APW, Argentina

Location

Clinica Viedma

Viedma, Río Negro Province, R8500ACE, Argentina

Location

Centro Medico San Roque

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

Location

Fundacion Favaloro

Ciudad de Buenos Aires, 1093, Argentina

Location

Fundación CORI para la Investigación y Prevención del Cáncer

La Rioja, F5300COE, Argentina

Location

Centro Polivalente de Asistencia e Inv. Clinica CER-San Juan

San Juan, J5402DIL, Argentina

Location

Calvary Mater Newcastle

Waratah, New South Wales, 2298, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Landesklinikum Wr. Neustadt

Wiener Neustadt, Lower Austria, 2700, Austria

Location

Universitätsklinikum Salzburg

Salzburg, 5020, Austria

Location

KH der Barmherzigen Brüder Wien

Vienna, 1020, Austria

Location

Cliniques universitaires Saint-Luc

Brussels, Brussels Capital, 1200, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Masarykuv onkologicky ustav

Brno, Brno-město, 656 53, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Fakultni Nemocnice v Motole

Prague, 150 06, Czechia

Location

Aarhus Universitetshospital, Aarhus Sygehus

Aarhus C, 8000, Denmark

Location

Odense Universitetshospital

Odense C, 5000, Denmark

Location

Centre Leon Berard

Lyon, Auvergne-Rhône-Alpes, 69008, France

Location

CHU de Bordeaux Hop St ANDRE

Bordeaux, Gironde, 33075, France

Location

CHU de Besancon Hopital Jean Minjoz

Besançon, 25030, France

Location

Hôpital C. HURIEZ

Lille, 59037, France

Location

CHRU de Montpellier-Hopital St Eloi

Montpellier, 34295, France

Location

Centre Antoine-Lacassagne

Nice, 06189, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Universitätsklinikum Tübingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Universitätsklinikum Erlangen

Erlangen, Bavaria, 91054, Germany

Location

Medizinische Hochschule Hanover

Hanover, Lower Saxony, 30625, Germany

Location

HELIOS Klinikum Berlin-Buch

Berlin, 13125, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Debreceni Egyetem Klinikai Kozpont Onkologiai Tanszek

Debrecen, Hajdú-Bihar, 4032, Hungary

Location

Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet

Budapest, 1097, Hungary

Location

Arke Estudios Clinicos S.A. de C.V.

Mexico City, Mexico City, 06700, Mexico

Location

Centro de Alta Especialidad Reumatologia Inv del Potosi SC

San Luis Potosí City, 78213, Mexico

Location

Russian Scientific Center of Radiology and Surgical Technologies

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

Arkhangelsk Clinical Oncological Dispensary

Arkhangelsk, 163045, Russia

Location

Blokhin Cancer Research Center

Moscow, 115478, Russia

Location

Saint-Petersburg City Clinical Oncology Dispensary

Saint Petersburg, 198255, Russia

Location

Asan Medical Center

Seoul, Korea, 05505, South Korea

Location

Seoul National University Hospital

Seoul, Seoul, Korea, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital Duran I Reynals

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Clínico Universitario de Valencia

Barcelona, 46010, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Clinico de San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Skåne universitetssjukhus

Malmo, 20502, Sweden

Location

Karolinska Universitetssjukhuset i Solna

Stockholm, 17176, Sweden

Location

Chang Gung Memorial Hospital - Kaohsiung Branch

Kaohsiung City, 83301, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Cheng-Kung Uni. Hosp.

Tainan, 704, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Chang Gung Memorial Hospital - Linkou

Taoyuan, 33305, Taiwan

Location

Baskent University Dr. Turgut Noyan Research and Training Center

Adana, 1250, Turkey (Türkiye)

Location

Hacettepe University Faculty of Medicine

Ankara, 06100, Turkey (Türkiye)

Location

Akdeniz University Medical Faculty

Antalya, 07059, Turkey (Türkiye)

Location

Trakya University

Edirne, 22030, Turkey (Türkiye)

Location

Istanbul Universitesi-Cerrahpasa Cerrahpasa Tip Fakultesi Yerleskesi

Istanbul, 34098, Turkey (Türkiye)

Location

University College Hospital - London

London, Greater London, NW1 2BU, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

Hammersmith Hospital

Acton, London, W12 0HS, United Kingdom

Location

The Clatterbridge Cancer Centre

Bebbington, Merseyside, CH63 4JY, United Kingdom

Location

Royal Marsden Hospital

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34592180 DERIVED

Related Links

• A Study of Ramucirumab (LY3009806) or Merestinib (LY2801653) in Advanced or Metastatic Biliary Tract Cancer

MeSH Terms

Conditions

Biliary Tract Neoplasms; Neoplasm Metastasis

Interventions

Ramucirumab; merestinib; Cisplatin; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2016
• First Posted: March 17, 2016
• Study Start: May 19, 2016
• Primary Completion: February 16, 2018
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 3, 2025
• Results First Posted: February 26, 2021

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: 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.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

AR (8); DK (2); AU (3); ME (2); ES (5); TW (5); CZ (3); US (13); HU (2); DE (6); FR (7); RU (4); SE (2); TU (5); GB (5); KR (4); BE (3)