Biomarker-Integrated Umbrella, Advanced Gastric Cancer

Yonsei University

Status: Completed

Conditions: Gastric Cancer

Treatments: Other: biomarker screening

Study type: Interventional

Funder types: Other

Identifiers

NCT02951091

4-2015-0616

Details and patient eligibility

About

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.

Full 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.

Enrollment: 400 patients

Sex: All

Ages: 19+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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400 participants in 2 patient groups

biomarker group

Experimental group

Description:

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.

Treatment:

Other: biomarker screening

control group

Active Comparator group

Description:

Patients will be randomized to the biomarker vs control group (standard of care; paclitaxel) as 4:1 ratio.

Treatment:

Other: biomarker screening