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

• ClinicalTrials.gov Identifier: NCT02731313
• Recruitment Status: Completed
• First Posted: April 7, 2016
• Results First Posted: October 28, 2016
• Last Update Posted: October 28, 2016
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

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+.

Condition or disease	Intervention/treatment
Gastric Cancer, Gastroesophageal Junction Cancer	Biological: Trastuzumab

Study Design

• Study Type: Observational
• Actual Enrollment: 420 participants
• Observational Model: Case-Only
• Time Perspective: Cross-Sectional
• Official Title: Evaluation of Human HER-2 Status in Gastric and Gastro-Oesophageal Junction Cancer.
• Study Start Date: July 2012
• Actual Primary Completion Date: October 2014
• Actual Study Completion Date: October 2014

Groups and Cohorts

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 Name: Herceptin

Outcome Measures

Primary Outcome Measures :

1. Simple Kappa Coefficient of Human Epidermal Growth Factor Receptor 2 (HER-2) Status Between Local and Centralized Laboratory Assessments [ Time Frame: At enrollment ]
   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.

Secondary Outcome Measures :

1. Cancer Characteristics: Percentage of Participants With Initial Location of Adenocarcinoma in Stomach Versus Esogastric Location [ Time Frame: At enrollment ]
2. Cancer Characteristics: Percentage of Participants With Samples in Each of the Histologic Type Lauren's Classifications, Including Diffuse Type, Intestinal and Mixed [ Time Frame: At enrollment ]
   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.
3. Cancer Characteristics: Percentage of Participants With Samples in Each of the Tumor-Node-Metastasis (TNM) Stages [ Time Frame: At enrollment ]
   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.
4. Weighted Kappa Coefficient Between Immunohistochemistry (IHC) 4B5 and Silver in Situ Hybridization (SISH) Techniques for HER-2 Testing in Centralized Laboratories [ Time Frame: At enrollment ]
   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.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

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

Criteria

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

Contacts and Locations

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, 13273

Marseille, France, 13385

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

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02731313
• Other Study ID Numbers: ML27940
• First Posted: April 7, 2016
• Results First Posted: October 28, 2016
• Last Update Posted: October 28, 2016
• Last Verified: September 2016

Additional relevant MeSH terms:

Stomach Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Trastuzumab; Antineoplastic Agents, Immunological; Antineoplastic Agents