An Efficacy Study in Gastric and Gastroesophageal Junction Cancer Comparing Ipilimumab Versus Standard of Care Immediately Following First Line Chemotherapy

Study Overview
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Brief Summary
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The purpose of the study is to compare the efficacy of Ipilimumab and standard of care as sequential or maintenance treatment immediately after first-line chemotherapy in the treatment of unresectable or metastatic gastric and gastro-esophageal cancer.

Official Title
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A Randomized, Open-label, Two-arm Phase II Trial Comparing the Efficacy of Sequential Ipilimumab Versus Best Supportive Care Following First-line Chemotherapy in Subjects With Unresectable Locally Advanced/Metastatic Gastric or Gastro-esophageal Junction Cancer

Conditions
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Locally Advanced (Unresectable) or Metastatic Adenocarcinoma of the Gastric and Gastro-esophageal Junction

Intervention / Treatment
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* Biological: Ipilimumab
* Other: Best Supportive care (BSC)


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Key Inclusion Criteria: Histologically confirmed, unresectable locally advanced or metastatic adenocarcinoma of the gastric and gastro-esophageal junction Received first-line chemotherapy using fluoropyrimidine and platinum combination without disease progression Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Measurable disease by modified WHO criteria (unless complete response from previous chemotherapy) Key Exclusion Criteria: Known Human Epidermal growth factor Receptor2 (HER2) positive status Radiological evidence of brain metastases History of severe autoimmune or immune mediated disease requiring prolonged immunosuppressive treatment Inadequate hematologic, renal and hepatic function

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Ipilimumab<br>Ipilimumab 10 mg/kg solution intravenously, 90 minute infusion, once every 3 weeks for 4 doses, then every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose) | Biological: Ipilimumab<br> <br> * Other names: BMS-734016;|
| Other: Arm B: Best Supportive care (BSC)<br>BSC may include the continuation of the Fluoropyrimidine that was used during the lead-in chemotherapy, but no other systemic anti cancer therapy | Other: Best Supportive care (BSC)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune-related Progression Free Survival (irPFS) as Per Assessment of a Blinded Independent Review Committee (IRC) According to Immune Related Response Criteria (irRC) Guidelines | irPFS is defined as the time between the randomization date and the time of disease progression per irRC or death, whichever occurs first. irRC criteria=Measurable new lesions: incorporated into the tumor burden (eg, added to the index lesions); do not define progression unless the total measurable tumor burden increases by the required amount (25%). New non-measurable lesions: not considered progression if the total measurable tumor burden is stable or shrinking. irPFS was measured in months. | Randomization up to 91 irPFS events (Approximately 19 months ) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) Per Modified World Health Organization (mWHO) Criteria | PFS per mWHO was defined as the time between the randomization date and the time of disease progression per mWHO criteria or death, whichever occurred first and was measured in months. mWHO criteria: New lesions always mean progression; Changes in non-measurable lesions contribute in the definitions of Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD). | Randomization up to 91 irPFS events (Approximately 19 months ) | 
| Overall Survival (OS) at Primary Endpoint | OS was defined as the time from the date of randomization until the date of death. For those participants who have not died, OS was censored on the last date the participant was known to be alive. | Randomization up to 91 irPFS events (Approximately 19 months) | 
| Overall Survival (OS) at Study Completion | OS was defined as the time from the date of randomization until the date of death. For those participants who have not died, OS was censored on the last date the participant was known to be alive. | Randomization up to end of study, April 2015 (Approximately 28 months) | 
| Percentage of Participants With Immune-Related Best Overall Response (irBOR) | IrBOR rate was defined as the number of participants whose Immune-related Best Overall Response (irBOR) criteria was Immune-related Complete Response (irCR) or Immune-related Partial Response (irPR), divided by the total number of participants. The immune-related sum of products of diameters (irSPD) incorporates - in addition to the index lesions - measurable new lesions that may have developed on-study, providing an assessment that includes both index and new lesions. irCR=Complete disappearance of all tumor lesions (both index and non-index lesions with no new measurable/unmeasurable lesions). irPR=A 50% or greater decrease, relative to baseline of the irSPD, (based on irSPD of all index lesions and any measurable new lesions). | Randomization up to 91 irPFS events (Approximately 19 months) |