Biomarker-Integrated Umbrella, Advanced Gastric Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer
• Intervention / Treatment: Other: biomarker screening

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 400
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital, Yonsei University Health System, Yonsei Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed locally advanced or metastatic gastric cancer and gastroesophageal junction cancer
2. Eastern Cooperative Oncology Group performance status of 0 to 1
3. Male or female; ≥ 19 years of age
4. On or progression after 1st line palliative chemotherapy
5. Subjects with evaluable lesion (using RECIST 1.1 criteria)

6. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: biomarker group; 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; immunohistochemistry and in situ hybridization
Active Comparator: control group; Patients will be randomized to the biomarker vs control group (standard of care; paclitaxel) as 4:1 ratio.	Other: biomarker screening; immunohistochemistry and in situ hybridization

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Sun Young Rha, Ph.D, Severance Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): March 1, 2024

Study Registration Dates

• First Submitted: October 28, 2016
• First Submitted That Met QC Criteria: October 31, 2016
• First Posted (Estimated): November 1, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: 4-2015-0616

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No