A Study of Paclitaxel With or Without Ramucirumab in Metastatic Gastric Adenocarcinoma (RAINBOW)

• Overall survival time (OS) [ Time Frame: Approximately 32 months ] [ Designated as safety issue: No ]
  Overall survival time is measured as randomization to date of death from any cause.
  
  

• Progression-free survival (PFS) [ Time Frame: Approximately 32 months ] [ Designated as safety issue: No ]
  PFS is measured from randomization to the first radiographically documented progressive disease (PD) or death.
  
  
• Time to progressive disease (TTP) [ Time Frame: Approximately 32 months ] [ Designated as safety issue: No ]
  TTP is the time from randomization to the first radiographically documented progressive disease.
  
  
• Best overall response (BOR) [ Time Frame: Approximately 32 months ] [ Designated as safety issue: No ]
  Number of participants whose best response is categorized as determined using the Response Evaluation Criteria In Solid Tumors (RECIST) (ver 1.1) guidelines.
  
  
• Objective response (ORR) [ Time Frame: Approximately 32 months ] [ Designated as safety issue: No ]
  Proportion of participants who achieved a best overall response of complete response (CR) or partial response (PR) compared to the total number of participants. Best response is categorized using the Response Evaluation Criteria In Solid Tumors (RECIST) (ver 1.1) guidelines.
  
  
• Serum Anti-Ramucirumab Antibody Assessment (Immunogenicity) [ Time Frame: 32 months ] [ Designated as safety issue: No ]
  This assessment will only be done at specific time points i.e. Prior to (within Pretreatment period) and after first ramucirumab infusion, prior to and after fourth ramucirumab infusion (approx. week 6 after first dose), prior to and after seventh ramucirumab infusion (approx. week 12 after first dose) and 30-37 days after last dose of study therapy.
  
  
• Maximum concentration (Cmax) after first ramucirumab infusion [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  Maximum concentration (Cmax) is the maximum peak concentration measured in blood serum after first ramucirumab infusion.
  
  
• Maximum concentration (Cmax) after 4th ramucirumab infusion [ Time Frame: Approximately week 6 (Cycle 2, Day 15) ] [ Designated as safety issue: No ]
  Maximum concentration (Cmax) is the maximum peak concentration measured in blood serum after 4th ramucirumab infusion.
  
  
• Maximum concentration (Cmax) after 7th ramucirumab infusion [ Time Frame: Approximately week 12 (Cycle 4, Day 1) ] [ Designated as safety issue: No ]
  Maximum concentration (Cmax) is the maximum peak concentration measured in blood serum after 7th ramucirumab infusion.
  
  
• Minimum concentration (Cmin) prior to first ramucirumab infusion [ Time Frame: within the pretreatment period until Day 1 ] [ Designated as safety issue: No ]
  Minimum concentration (Cmin) is the minimum trough concentration measured in blood serum prior to first ramucirumab infusion.
  
  
• Minimum concentration (Cmin) prior to 4th ramucirumab infusion [ Time Frame: Approximately week 6 (Cycle 2, Day 15) ] [ Designated as safety issue: No ]
  Minimum concentration (Cmin) is the minimum trough concentration measured in blood serum prior to 4th ramucirumab infusion.
  
  
• Minimum concentration (Cmin) prior to 7th ramucirumab infusion [ Time Frame: Approximately week 12 (Cycle 4, Day 1) ] [ Designated as safety issue: No ]
  Minimum concentration (Cmin) is the minimum trough concentration measured in blood serum prior to 7th ramucirumab infusion.
  
  
• Change in European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 [ Time Frame: 32 months ] [ Designated as safety issue: No ]
  Change from baseline in the patient reported outcomes measured at the end of therapy visit
  
  
• Change in EuroQol EQ-5D [ Time Frame: 32 months ] [ Designated as safety issue: No ]
  Change from baseline to the end of therapy visit
  
  

The aim of this study is to determine if paclitaxel given together with ramucirumab as second line therapy will prolong overall survival compared to paclitaxel alone.

Approximately 663 patients (at least 18 years) in approximately 200 study centers and in approximately 30 countries will be randomized with histologically or cytologically confirmed metastatic gastric or gastroesophageal junction adenocarcinoma. Patients must have received at least one cycle of first line therapy with any platinum/fluoropyrimidine doublet with or without anthracycline (epirubicin or doxorubicin) and must have discontinued this therapy prior to study entry due to disease progression.

Upon registration and completion of screening procedure and reviewing the Inclusion and Exclusion Criteria eligible patients will be randomized to receive either paclitaxel plus ramucirumab or paclitaxel plus placebo.

Ramucirumab DP/placebo will be administered i.v. on days 1 and 15 , paclitaxel will be administered i.v. on days 1, 8 and 15 of a 4 weekly cycle.

Patients will be continuously treated and monitored until radiographic or symptomatic progression of disease, toxicity requiring cessation, protocol noncompliance, or withdrawal of consent.