Biomarker-Integrated Umbrella, Advanced Gastric Cancer

Study Overview
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Brief Summary
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In-depth understanding of molecular characteristics of gastric cancer enabled us to realize personalized medicine with targeted agents in gastric cancer treatment.The investigators initiated open-label, randomized, controlled phase II, multi-arm trial comparing targeted therapy based on tumor molecular profiling with standard paclitaxel therapy as second line treatment.

Official Title
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The Master Protocol for Biomarker-Integrated Umbrella Trial in Advanced Gastric Cancer

Conditions
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Gastric Cancer

Intervention / Treatment
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* Other: biomarker screening


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed locally advanced or metastatic gastric cancer and gastroesophageal junction cancer Eastern Cooperative Oncology Group performance status of 0 to 1 Male or female; ≥ 19 years of age On or progression after 1st line palliative chemotherapy Subjects with evaluable lesion (using RECIST 1.1 criteria) Subjects who meet the following criteria: Absolute neutrophil count ≥ 1000 /µL Platelet count ≥ 75,000/ µL Serum creatinine < 1.5 x upper limit of normal or Creatinine clearance ≥60 mL/min aspartate aminotransferase and alanine transaminase 3 x upper limit of normal Exclusion Criteria: Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study

Ages Eligible for Study
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Minimum Age: 19 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
Interventional Model Description: Biomarker-integrated multi-arm with shared standard of care (SOC) control arm
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: biomarker group<br>400 Her-2 (-) metastatic/recurrent gastric cancer patients will be centrally screened for druggable targets [Epstein-Barr virus, Microsatellite instability, HER2, EGFR, c-MET, and PTEN] by immunohistochemistry and in situ hybridization during first line chemotherapy. At the time of second line treatment, patients will be randomized to the biomarker vs control group as 4: 1 ratio. The biomarker group will be offered for entry into a specific protocol based on their molecular cohort and treated with specific targeted agents in combination with weekly paclitaxel; 1) EGFR cohort (EGFR 2+ or EGFR 3+) for pan-ERBB inhibitor (afatinib), 2)PTEN loss cohort (PTEN score less than 100) for PIK3CB inhibitor (GSK2636771), 3) PD-L1 positive, MSI-high, or EBV positive cases for nivolumab, 4) none for weekly paclitaxel. | Other: biomarker screening<br>* immunohistochemistry and in situ hybridization<br>|
| Active Comparator: control group<br>Patients will be randomized to the biomarker vs control group (standard of care; paclitaxel) as 4:1 ratio. | Other: biomarker screening<br>* immunohistochemistry and in situ hybridization<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival |  | 6 weeks |