A Study of Ramucirumab in Treating Japanese Participants With Metastatic Gastric or Gastroesophageal Junction Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate progression-free survival in participants with gastric or gastroesophageal junction cancer who have had disease progression following first-line therapy who undergo treatment with ramucirumab.

Official Title
-----------------
A Phase 2 Study of Ramucirumab in the Treatment of Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Following Disease Progression on First Line Platinum- or Fluoropyrimidine-Containing Combination Therapy in Japanese Patients

Conditions
-----------------
Gastric Cancer

Intervention / Treatment
-----------------
* Drug: Ramucirumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed gastric carcinoma, including gastric adenocarcinoma or Gastroesophageal Junction (GEJ) adenocarcinoma Metastatic disease or locally recurrent, unresectable disease Measurable disease and/or evaluable disease Experienced disease progression during or within 4 months after the last dose of first-line therapy for metastatic disease, or during or within 6 months after the last dose of adjuvant therapy Life expectancy of at least 3 months Resolution to Grade less than or equal to 1 by the National Cancer Institute Common Terminology Criteria for Adverse , Version 4.03, of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy Eastern Cooperative Oncology Group performance status score of 0-1 Has adequate organ function Must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods), if sexually active Female participants of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment Exclusion Criteria: Documented and/or symptomatic brain or leptomeningeal metastases Bone metastases Experienced Grade 3/4 gastrointestinal (GI) bleeding within 3 months prior to enrollment Experienced any arterial thromboembolic event within 6 months prior to enrollment Ongoing or active significant infection, symptomatic congestive heart failure (CHF), unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, uncontrolled thromboembolic or hemorrhagic disorder, or any other serious uncontrolled medical disorders in the opinion of the investigator Ongoing or active psychiatric illness or social situation that would limit compliance with study requirements Blood pressure in abnormal range despite standard medical management Has a serious or nonhealing wound, ulcer, or bone fracture Received chemotherapy, radiotherapy, immunotherapy, or targeted therapy for gastric cancer Received any investigational therapy within 30 days prior to enrollment Undergone major surgery within 28 days prior to enrollment, or subcutaneous venous access device placement within 7 days prior to enrollment Received prior therapy with an agent that directly inhibits vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor 2 (VEGFR-2) activity (including bevacizumab), or any anti-angiogenic agent Receiving chronic therapy with nonsteroidal anti-inflammatory drugs or receiving other antiplatelet agents. Aspirin use at doses up to 325 milligrams per day is permitted Has elective or planned major surgery to be performed during the course of the clinical study Has a known allergy to any of the treatment components Pregnant or breastfeeding Have positive test results for human immunodeficiency virus, hepatitis B, or hepatitis C antibodies Known alcohol or drug dependency Previous or concurrent malignancy except for basal or squamous cell skin cancer (nonmelanoma) and/or pre-invasive carcinoma of the cervix, mucosal gastrointestinal or uterine carcinoma, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to enrollment Currently enrolled in a clinical trial involving an investigational product or non-approved use of a drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ramucirumab<br>Ramucirumab 8 milligrams per kilogram (mg/kg) administered intravenously (IV) once every 2 weeks. Treatment will continue until there is evidence of progressive disease (PD), the development of unacceptable toxicity, protocol noncompliance or withdrawal of consent. | Drug: Ramucirumab<br>* Administered IV<br>* Other names: IMC-1121B;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Are Progression-Free at 12 Weeks (Progression-Free Survival [PFS] Rate at 12 Weeks) | The 12-week PFS rate is the probability of participants who survived during the first 12 weeks in the study without disease progression. It was estimated using the Kaplan-Meier method for the main analysis of the 12-week PFS rate. | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | The time from baseline to measured Progressive Disease (PD) as defined by RECIST v.1.1 [defined as > 20% increase from smallest sum of longest diameter recorded since treatment started (best response)], or death due to any cause, whichever is first. | Baseline to Measured PD or Death from Any Cause (Up to 30.3 weeks) | 
| Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] | Participants achieved an objective response if they had a best overall response of CR or PR. According to RECIST v1.1, PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter; CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to <10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels [if tumor markers were initially above the upper limit of normal (ULN)]. The percentage of participants who achieved an objective response = (number of participants with CR or PR)/(number of participants assessed)*100. | Baseline to Measured PD or Death from Any Cause (Up to 38.0 Weeks) | 
| Percentage of Participants Achieving Stable Disease (SD) or a Confirmed CR or PR [Disease Control Rate (DCR)] | Participants achieved disease control if they had a best overall response of CR, PR or SD. According to RECIST v1.1, CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to <10 mm, the disappearance of all non-target lesions, and the normalization of tumor marker levels (if tumor markers were initially above the ULN); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started. The percentage of participants who achieved disease control = (number of participants with CR, PR, or SD)/(number of participants assessed)*100. | Baseline to Measured PD or Death from Any Cause (Up to 12 Months) | 
| Overall Survival (OS) | The OS time is defined as the time from baseline to the date of death from any cause. If a participant is not known to have died on or before the date of data cut-off, OS data will be censored on the last date (on or before the cut-off date) the participant was known to be alive. | Baseline to Death from Any Cause (Up to 13 Months) | 
| Number of Participants With Anti-Ramucirumab Antibodies | A sample will be considered positive for circulating anti-ramucirumab antibodies if it exhibits a post-baseline antibody level that exceeds the upper 95% confidence interval of the mean determined from the normal anti-ramucirumab level seen in healthy untreated individuals. A participant will be considered to have an anti-ramucirumab response if there are 2 consecutive positive samples or if the final sample tested is positive. | Cycle 1: Pre-infusion, Cycle 2: Pre-infusion, Cycle 3: Pre-infusion, Follow Up | 
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab |  | Cycle 1 Day 1: Pre-Dose, End of Infusion. 1, 4, 23, 47, 95, 167, 263, and 335 Hours Post-Dose | 
| PK: Area Under the Curve Time Zero to Infinity (AUC[0-∞]) of Ramucirumab |  | Cycle 1 Day 1: Pre-Dose, End of Infusion: 1, 4, 23, 47, 95, 167, 263, and 335 Hours Post-Dose |