Human Epidermal Growth Factor Receptor 2 (HER-2) Status in Gastric and Gastro-Esophageal Junction (GEJ) Carcinoma

Evaluation of Human HER-2 Status in Gastric and Gastro-Oesophageal Junction Cancer.

The primary objective is to evaluate the concordance between human epidermal growth factor receptor 2 (HER2) status determined by the participating laboratory and by the centralized laboratory. HER2 status of samples was tested by the participating laboratories (investigator's choice of immunohistochemistry [IHC] and in situ hybridization [ISH] methods) and by the centralized laboratories (IHC using the 4B5 anti-HER antibody and Silver ISH). Positive HER2 status was defined as a score of IHC3+ or IHC2+/ISH+.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer, Gastroesophageal Junction Cancer
• Intervention / Treatment: Biological: Trastuzumab

• Study Type: Observational
• Enrollment (Actual): 420

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80054
  • Besancon, France, 25030
  • Boulogne Billancourt, France, 92104
  • Brest, France, 29609
  • Clichy, France, 92118
  • Douai, France, 59500
  • La Tronche, France, 38700
  • Le Pontet, France, 84130
  • Marseille, France, 13385
  • Marseille, France, 13273
  • Montpellier, France, 34295
  • Montpellier, France, 34298
  • Nantes, France, 44093
  • Paris, France, 75571
  • Paris, France, 75679
  • Pessac, France, 33604
  • Reims, France, 51092
  • Rennes, France, 35000
  • Rouen, France, 76031

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Tumor samples from participants with gastric and gastro-esophageal junction (GEJ) carcinoma.

Description

Inclusion Criteria:

• Tumor samples with histologically confirmed gastric or gastro-esophageal junction (GEJ) adenocarcinoma, any stage
• Samples with sufficient tumor material for centralized analysis
• Samples fixed and embedded in paraffin (formalin-fixed paraffin-embedded tissue [FFPET] samples).

Exclusion Criteria:

- Fixatives not allowed: Bouin's solution

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Gastric and Gastro-Esophageal Junction (GEJ) Carcinoma; Tumor samples with histologically confirmed gastric or GEJ adenocarcinoma, any stage, were collected and analyzed. No study visits or interventions were planned.	Biological: Trastuzumab; Trastuzumab was not administered in this study. This study informs future trastuzumab treatment decisions.; Other Names: Herceptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Simple Kappa Coefficient of Human Epidermal Growth Factor Receptor 2 (HER-2) Status Between Local and Centralized Laboratory Assessments	Positive HER-2 status was defined as either immunohistochemistry (IHC) score of 3+ or IHC score 2+/in situ hybridization (ISH) score +, as per the trastuzumab Summary of Product Characteristics (SPC). The HER-2 status in tumor specimens was determined using the pathologist's choice of IHC and ISH techniques in local laboratories, and using IHC 4B5 and silver ISH (SISH) in centralized laboratories. The kappa coefficient was used to evaluate the true concordance between the HER-2 status determined by local and centralized laboratories. The kappa coefficient value was interpreted according to the Landis and Koch classification as follows: a) less than (<) 0: less than chance agreement, b) 0.01-0.20: slight agreement, c) 0.21-0.40: fair agreement, d) 0.41-0.60: moderate agreement, e) 0.61-0.80: substantial agreement, and f) 0.81-0.99: almost perfect agreement.	At enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cancer Characteristics: Percentage of Participants With Initial Location of Adenocarcinoma in Stomach Versus Esogastric Location		At enrollment
Cancer Characteristics: Percentage of Participants With Samples in Each of the Histologic Type Lauren's Classifications, Including Diffuse Type, Intestinal and Mixed	The Lauren classification is based on examination of histologic specimens under the microscope and divides adenocarcinoma of the stomach into 3 types: 1) Diffuse type: tumor cells are poorly differentiated, behave aggressively and tend to scatter throughout the stomach (rather than form glands). This type metastasizes to other parts of the body much quicker than intestinal type tumors, 2) Intestinal type: tumor cells are well differentiated, grow slowly and tend to form glands, 3) Mixed type: this type is made up of both intestinal and diffuse types.	At enrollment
Cancer Characteristics: Percentage of Participants With Samples in Each of the Tumor-Node-Metastasis (TNM) Stages	The TNM stage system includes information about the size of the primary tumor (T), whether the cancer has spread to nearby lymph nodes (N) and whether the cancer has metastasized to other parts of the body (M). In the T classification TX indicates that the main tumor cannot be measured, T1, T2, T3 and T4 refer to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues. In the N classification NX indicates that the cancer in nearby lymph nodes cannot be measured, N0 indicates that there is no cancer in nearby lymph nodes, N1, N2 and N3 refer to the number and location of lymph nodes that contain cancer. The higher the number after the N, the more lymph nodes that contain cancer. In the M classification MX indicates that the metastasis cannot be measured, M0 indicates that the cancer has not spread to other parts of the body and M1 indicates that the cancer has spread to other parts of the body.	At enrollment
Weighted Kappa Coefficient Between Immunohistochemistry (IHC) 4B5 and Silver in Situ Hybridization (SISH) Techniques for HER-2 Testing in Centralized Laboratories	Positive HER-2 status was defined as either immunohistochemistry (IHC) score of 3+ or IHC score 2+/in situ hybridization (ISH) score +, as per the trastuzumab Summary of Product Characteristics (SPC). The HER-2 status in tumor specimens was determined using IHC 4B5 and silver ISH (SISH) in centralized laboratories. The weighted kappa coefficient was used to evaluate the true concordance between the HER-2 status determined by IHC 4B5 and SISH. The weighted kappa coefficient value was interpreted according to the Landis and Koch classification as follows: a) less than (<) 0: less than chance agreement, b) 0.01-0.20: slight agreement, c) 0.21-0.40: fair agreement, d) 0.41-0.60: moderate agreement, e) 0.61-0.80: substantial agreement, and f) 0.81-0.99: almost perfect agreement.	At enrollment

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: March 24, 2016
• First Submitted That Met QC Criteria: April 2, 2016
• First Posted (Estimate): April 7, 2016

Study Record Updates

• Last Update Posted (Estimate): October 28, 2016
• Last Update Submitted That Met QC Criteria: September 8, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: ML27940