Second-Line Metastatic or Locally Advanced, Unresectable Gastric or Gastroesophageal Junction Adenocarcinoma MedDRA version: 20.0 Level: PT Classification code 10063916 Term: Metastatic gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [1] The patient has a histopathologically or cytologically confirmed diagnosis of gastric or GEJ (Siewert Types I-III) adenocarcinoma. [2] The patient 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. [3] The patient 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 (either approved or experimental treatment). [4] The patient has metastatic disease or locally advanced disease that is evaluable, by radiological imaging per RECIST 1.1. [5] The patient has an ECOG performance status of 0 or 1. [6] The patient has adequate organ function, including: a. Total bilirubin equal to or less than 1.5 × the upper limit of institutional normal (ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less or equal 3 × ULN. If the liver has tumor involvement, AST and ALT =65 years) yes F.1.3.1 Number of subjects for this age range 96
Exclusion criteria
Exclusion criteria: [1] The patient has cancer with histology other than adenocarcinoma. [2] The patient is receiving chronic therapy with any of the following within 7 days prior to randomization: a. nonsteroidal anti-inflammatory agents (NSAIDs; such as indomethacin, ibuprofen, naproxen, or similar agents) b. other anti-platelet agents (such as clopidogrel, ticlopidine, dipyridamole, or anagrelide); Aspirin use at doses up to 325 mg/day is permitted. [3] The patient received radiotherapy within 14 days prior to randomization. Palliative radiotherapy during the study, if clinically indicated, can be considered after consultation with the Lilly clinical research physician (CRP). Any lesion requiring palliative radiotherapy or which has been previously irradiated cannot be considered for response assessment. [4] The patient received >1 line of prior therapy for the treatment of locally advanced and unresectable or metastatic gastric or GEJ (Siewert Types I-III) adenocarcinoma. [5] The patient received previous systemic chemotherapy with a cumulative dose of >900 mg/m2 of epirubicin or >400 mg/m2 of doxorubicin. [6] The patient received previous treatment with agents targeting the VEGF/VEGF Receptor 2 signaling pathway, including previous exposure to ramucirumab. [7] The patient has documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression. Screening of asymptomatic patients is not required. [8] The patient has a significant bleeding disorder or vasculitis or had a Grade 3 or more bleeding episode within 12 weeks prior to randomization. [9] The patient experienced any arterial thromboembolic event (ATE), including myocardial infarction, unstable angina, cerebrovascular accident , or transient ischemic attack, within 6 months prior to randomization. [10] The patient has symptomatic congestive heart failure (CHF; New York Heart Association II-IV) or symptomatic or poorly controlled cardiac arrhythmia. [11] The patient has uncontrolled hypertension, as defined in CTCAE Version 4.0, prior to initiating study treatment, despite antihypertensive intervention. [12] The patient underwent major surgery within 28 days prior to randomization or central venous access device placement within 7 days prior to randomization. [13] The patient plans to undergo elective major surgery during the course of the trial. [14] The patient has a history of gastrointestinal (GI) perforation or fistula within 6 months prior to randomization. [15] The patient has a history of inflammatory bowel disease or Crohn’s disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) within 12 months prior to randomization. [16] The patient has an acute or subacute bowel obstruction or history of chronic diarrhea that is considered clinically significant in the opinion of the investigator. [17] The patient has either of the following: a. cirrhosis at a level of Child-Pugh B (or worse) b. cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. [18] The patient has a serious illness or medical condition including, but not limited to, the following: a. known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness b. active or uncontrolled clinically serious infection [19] The patient is pregnant or breastfeeding. [20] The patient has a concurrent active m
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the efficacy of ramucirumab 12 mg/kg versus placebo, both in combination with paclitaxel, in terms of PFS;Secondary Objective: Evaluate the efficacy of ramucirumab 12 mg/kg versus 8 mg/kg, both in combination with paclitaxel, in terms of PFS PK of ramucirumab in combination with paclitaxel ORR, DRC, Immunogenicity;Primary end point(s): efficacy: PFS, as determined by investigator assessment per RECIST 1.1, (12 mg/kg versus placebo) ;Timepoint(s) of evaluation of this end point: The final analysis of the primary endpoints will occur after 191 randomized patients have completed (Progression Free Survival Event) or discontinued for any reason prior to completing. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): efficacy: PFS, as determined by investigator assessment per RECIST 1.1, (12 mg/kg versus ramucirumab 8 mg/kg) Minimum ramucirumab concentration in serum The safety endpoints evaluated will include but are not limited to the following: - TEAEs, AESIs, SAEs, and hospitalizations - Clinical laboratory tests, vital signs, and physical examinations - ORR, DCR - Blood samples for immunogenicity testing will be collected to determine antibody production against ramucirumab;Timepoint(s) of evaluation of this end point: The final analysis of the secondary endpoints will occur after 191 randomized patients have completed (Progression Free Survival Event) or discontinued for any reason prior to completing. | — |
Countries
Belgium, Canada, Czech Republic, Germany, Greece, Spain, Sweden, Turkey, Ukraine, United States
Contacts
Public ContactClinical Trial Registry Office
Eli Lilly
Outcome results
None listed