A Phase 2 Study of Ramucirumab (LY3009806) in Participants With Gastric or Gastroesophageal Junction (GEJ) Cancer

Randomized Phase 2 Trial Evaluating Pharmacokinetics and Safety of Four Ramucirumab Dosing Regimens in Second-Line Gastric or Gastroesophageal Junction Adenocarcinoma

The main purpose of this study was to evaluate the safety and pharmacokinetics of administering various dose regimens of ramucirumab in participants with advanced gastric cancer whose disease has progressed during or following prior chemotherapy.

Study Overview

• Status: Completed
• Conditions: Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: Ramucirumab

• Study Type: Interventional
• Enrollment (Actual): 164
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1025
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Rosario, Argentina, 2000
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • San Miguel de Tucumán, Argentina, T4000IAK
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Viedma, Argentina, 8500
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Australia
  • Adelaide, Australia, 5000
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Kingswood, Australia, 2747
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Melbourne, Australia, 3144
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Nedlands, Australia, 6009
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• France
  • Brest, France, 29609
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Creteil, France, 94010
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Dijon, France, 21079
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Lyon, France, 69437
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Paris, France, 75013
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Paris, France, 75012
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Hungary
  • Budapest, Hungary, 1125
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Szolnok, Hungary, 5000
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• New Zealand
  • Auckland, New Zealand, 1023
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Christchurch, New Zealand, 8011
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Poland
  • Gdansk, Poland, 80-219
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Lodz, Poland, 90-242
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Poznan, Poland, 61-485
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Warszawa, Poland, 04-125
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Romania
  • Baia Mare, Romania, 430031
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
  • Cluj-Napoca, Romania, 400058
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
  • Craiova, Romania, 200347
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Arkhangelsk Regional Clinical Oncology Dispensary
  • Kursk, Russian Federation, 305035
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Moscow, Russian Federation, 115478
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • St. Petersburg, Russian Federation, 194291
    • Leningrad Regional Clinical Hospital
• Slovakia
  • Bratislava, Slovakia, 833 10
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
  • Kosice, Slovakia, 041-90
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
• Turkey
  • Edirne, Turkey, 22030
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Fatih, Turkey, 34093
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Pendik, Turkey, 34668
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Yüregir, Turkey, 1250
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• United Kingdom
  • Cardiff, United Kingdom, CF14 2TL
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Exeter, United Kingdom, EX2 5DW
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Leeds, United Kingdom, LS9 7TF
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Manchester, United Kingdom, M20 4BX
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Wolverhampton, United Kingdom, WV10 0QP
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• United States
  • Arizona
    • Tucson, Arizona, United States, 85715
      • Arizona Clinical Research Center
  • California
    • Los Angeles, California, United States, 90033
      • USC Norris Cancer Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Carolinas Medical Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74146
      • Oklahoma Cancer Specialists & Research Institute, LLC
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The participant has a histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ).
• The participant has documented disease progression during or within 4 months after the last dose of first-line chemotherapy for metastatic disease, or during or within 6 months after the last dose of neoadjuvant or adjuvant therapy.

• The participant received combination chemotherapy prior to disease progression.

  • Prior chemotherapy regimens must include a platinum and/or a fluoropyrimidine component and must not include a taxane or antiangiogenic agent.
• The participant has metastatic disease or locally advanced disease that is measurable or nonmeasurable, but is evaluable disease by radiological imaging per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1).
• Patients are eligible if they are considered not appropriate, for whatever reason, for treatment with ramucirumab in combination with paclitaxel.
• The participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• The participant has adequate organ function, including:

  • Total bilirubin 1.5 × the upper limit of institutional normal (ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 3 × ULN. If the liver has tumor involvement, AST and ALT <5 × ULN are acceptable.
  • Serum creatinine 1.5 × ULN or calculated creatinine clearance (per the Cockcroft-Gault formula or equivalent and/or 24-hour urine collection) 60 milliliters/minute (mL/min).
  • Urinary protein is <2+ on dipstick or routine urinalysis.
  • Absolute neutrophil count 1.5 × 10^9/Liter (L), platelets 100 × 10^9/L, and hemoglobin 9 g/deciliter (dL) (5.58 millimoles/Liter).
  • International normalized ratio 1.5 × ULN or prothrombin time 5 seconds above ULN.
  • Partial thromboplastin time 5 seconds above ULN.
• The participant has an estimated life expectancy of 12 weeks in the judgment of the investigator.
• The participant, if female and of child-bearing potential, must have a negative serum or urine pregnancy test within 7 days prior to randomization.

Exclusion Criteria:

• The participant has squamous cell or undifferentiated gastric cancer.

• The participant is receiving chronic therapy with any of the following within 7 days prior to randomization:

  • Nonsteroidal anti-inflammatory agents (NSAIDs; such as indomethacin, ibuprofen, naproxen, or similar agents), or
  • Other anti-platelet agents (such as clopidogrel, ticlopidine, dipyridamole, or anagrelide). Aspirin use at doses up to 325 milligrams (mg)/day is permitted.
• The participant received radiotherapy within 14 days prior to randomization.
• The participant received >1 line of prior therapy for the treatment of locally advanced and unresectable or metastatic gastric or GEJ (Siewert Types I-III) adenocarcinoma.
• The participant received previous treatment with agents targeting the vascular endothelial growth factor (VEGF)/VEGF receptor 2 signaling pathway.
• The participant has documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression.
• The participant experienced any arterial thromboembolic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization.
• The participant has symptomatic congestive heart failure (New York Heart Association II-IV) or symptomatic or poorly controlled cardiac arrhythmia.
• The participant has uncontrolled hypertension, as defined in Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0, prior to initiating study treatment, despite antihypertensive intervention.
• The participant underwent major surgery within 28 days prior to randomization or central venous access device placement within 7 days prior to randomization.
• The participant has a history of gastrointestinal perforation or fistula within 6 months prior to randomization.
• The participant has any condition (for example, psychological, geographical, or medical) that does not permit compliance with the study and follow-up procedures or suggests that the participant is, in the investigator's opinion, not an appropriate candidate for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ramucirumab Regimen 1; Standard dose of 8 milligram per kilogram (mg/kg) ramucirumab given intravenously (IV) on day 1 and day 15 of each cycle (28-day cycle) until discontinuation criteria are met.	Drug: Ramucirumab; Administered IV; Other Names: LY3009806; IMC-1121B
Experimental: Ramucirumab Regimen 2; Experimental dose of 12 mg/kg ramucirumab given IV on day 1 and day 15 of each cycle (28-day cycle) until discontinuation criteria are met.	Drug: Ramucirumab; Administered IV; Other Names: LY3009806; IMC-1121B
Experimental: Ramucirumab Regimen 3; Experimental dose of 6 mg/kg ramucirumab given IV on day 1, 8, 15 and 22 of each cycle (28-day cycle) until discontinuation criteria are met.	Drug: Ramucirumab; Administered IV; Other Names: LY3009806; IMC-1121B
Experimental: Ramucirumab Regimen 4; Experimental dose of 8 mg/kg ramucirumab given IV on day 1 and day 8 of each cycle (21-day cycle) until discontinuation criteria are met.	Drug: Ramucirumab; Administered IV; Other Names: LY3009806; IMC-1121B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab	The Cmin is the minimum observed serum concentration of ramucirumab.	Day 29, 43, 71 and 85: predose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity: Number of Participants With Anti-Ramucirumab Antibodies	Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group. A treatment-emergent anti-drug antibodies (TEADA) sample was defined as: a post treatment sample with at least a 4-fold increase in titer from pre treatment sample; or 1:20 post treatment titer for participants that had no detectable ADA titer at baseline.	Predose Cycle 1 Through Short Term Follow Up (Up to 5 Months)
Rate of Progression Free Survival (PFS) at the First 6-Week Tumor Assessment	PFS defined as the time from first day of therapy to first evidence of disease progression per response evaluation criteria in solid tumors version 1.1 (RECIST v1.1) or death from any cause up to the first 6-week tumor assessment. Progressive Disease (PD) is at least 20% increase in sum of diameters of target lesions,taking as reference smallest sum on study and absolute increase of at least 5 mm.Appearance of 1 or more new lesions was also considered progression. Nontarget PD is unequivocal progression of existing nontarget lesions.Appearance of 1 or more new nontarget lesions was also considered PD.Participants with no baseline disease assessment: PFS time was censored at the randomization date,regardless of whether or not objectively determined disease progression or death has been observed.	Baseline until the first 6-week tumor assessment

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2015
• Primary Completion (Actual): November 18, 2016
• Study Completion (Actual): June 5, 2019

Study Registration Dates

• First Submitted: May 12, 2015
• First Submitted That Met QC Criteria: May 12, 2015
• First Posted (Estimate): May 14, 2015

Study Record Updates

• Last Update Posted (Actual): June 29, 2020
• Last Update Submitted That Met QC Criteria: June 26, 2020
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: stomach cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Adenocarcinoma; Esophageal Neoplasms; Antineoplastic Agents; Ramucirumab
• Other Study ID Numbers: 15608; I4T-MC-JVDB (Other Identifier: Eli Lilly and Company); 2014-003791-23 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing 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.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR