Matuzumab Treatment With Epirubicin, Cisplatin and Capecitabine (ECX) in Esophago-Gastric Cancer

Study Overview
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Brief Summary
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The purpose of this study is to compare the effectiveness and safety of experimental treatment matuzumab and ECX chemotherapy, with ECX chemotherapy. Participants invited to take part have metastatic cancer of the esophagus (gullet) or stomach.

Official Title
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Randomized Phase II Open-Label Controlled Study of EMD 72000 (Matuzumab), in Combination With the Chemotherapy Regimen ECX or the Chemotherapy Regimen ECX Alone as First-line Treatment in Subjects With Metastatic Esophago-Gastric Adenocarcinoma

Conditions
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Esophageal Cancer, Gastric Cancer

Intervention / Treatment
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* Drug: Matuzumab
* Drug: Epirubicin
* Drug: Cisplatin
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed gastric adenocarcinoma or adenocarcinoma of the lower third of the esophagus Metastatic disease Immunohistological evidence of Epidermal Growth Factor Receptor (EGFR) expression from archived tissues Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1 At least 1 measurable lesion (modified World Health Organization criteria) Exclusion Criteria: Previous chemotherapy, unless neo-adjuvant or adjuvant therapy completed greater than (>) 12 months prior to study treatment Radiotherapy or major surgery within 4 weeks prior to treatment Brain metastases Peripheral neuropathy or ototoxicity greater than or equal to (>/=) Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events Version 3 [NCICTC V3]) Abnormal electrocardiogram (ECG)

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epirubicin, Cisplatin, Capecitabine (ECX)+Matuzumab<br> | Drug: Matuzumab<br>* Participants will receive matuzumab 800 milligrams (mg) intravenously (IV) every week, until disease progression (PD), unacceptable toxicity, death, or consent is withdrawn.<br>* Other names: EMD 72000;Drug: Epirubicin<br>* Participants will receive epirubicin 50 milligrams per square meter (mg/m^2) on Day 1 of 21-day cycle up to a maximum of 8 cycles.<br>Drug: Cisplatin<br>* Participants will receive cisplatin 60 mg/m^2 on Day 1 of 21-day cycle up to a maximum of 8 cycles.<br>Drug: Capecitabine<br>* Participants will receive capecitabine 1250 mg/m^2 daily in a 21-day cycles up to a maximum of 8 cycles.<br>|
| Active Comparator: ECX Only<br> | Drug: Epirubicin<br>* Participants will receive epirubicin 50 milligrams per square meter (mg/m^2) on Day 1 of 21-day cycle up to a maximum of 8 cycles.<br>Drug: Cisplatin<br>* Participants will receive cisplatin 60 mg/m^2 on Day 1 of 21-day cycle up to a maximum of 8 cycles.<br>Drug: Capecitabine<br>* Participants will receive capecitabine 1250 mg/m^2 daily in a 21-day cycles up to a maximum of 8 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Objective Response Assessed by Independent Review Committee | Objective response was defined as having a complete response (CR) or a partial response (PR). Response assessment was performed using modified World Health Organization (WHO) criteria. CR: disappearance of all index and non-index lesions, without appearance of any new lesion. PR: greater than (>) 50 percent (%) decrease from baseline in sum of product of diameters of index lesions, without appearance of any new lesion. | Baseline up to PD or death due to any cause (up to approximately 3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Objective Response Assessed by Independent Review Committee | Objective response was defined as having a CR or a PR. Response assessment was performed using modified WHO criteria. CR: disappearance of all index and non-index lesions, without appearance of any new lesion. PR: >50% decrease from baseline in sum of product of diameters of index lesions, without appearance of any new lesion. Duration of objective response was defined as time from first appearance of CR or PR to time of PD (PD: >25% increase in one or more lesions, or appearance new lesions) or death. Duration of objective response was to be assessed using Kaplan-Meier analysis. | From first documented objective response to PD or death due to any cause (up to approximately 3 years) | 
| Progression-Free Survival | PFS was defined as the time from randomization to the first documentation of PD or to death due to any cause, whichever occurred first. PD: >25% increase in one or more lesions, or appearance new lesions. PFS was estimated using Kaplan-Meier analysis. | Baseline up to PD or death due to any cause (up to approximately 3 years) | 
| Overall Survival (OS) | OS was defined as the duration from randomization to death (due to any cause). OS was estimated using Kaplan-Meier analysis. | Baseline until death due to any cause (up to approximately 3 years) | 
| Best Overall Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (GHS)/Quality of Life (QoL) Score | EORTC QLQ-C30 included GHS/QoL, functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Most questions from EORTC QLQ-C30 were a 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale and were a 7-point scale (1/Very Poor to 7/Excellent). For this instrument, GHS/QOL was linearly transformed and ranged 0-100, where lower scores indicate poorer functioning (e.g., worsening) and higher scores indicate better functioning (e.g., improvement). EORTC QLQ-C30 GHS/QoL score at baseline and best overall change from baseline (throughout study) are reported. | Baseline (Day 1), Post Baseline (Up to 3 Years) | 
| Protein Biomarkers Levels |  | Baseline up to approximately 3 years | 
| Percentage of Participants With Anti-Matuzumab Antibodies |  | Baseline up to approximately 3 years | 
| Matuzumab Serum Concentration |  | Baseline up to approximately 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Esophagus, Gastric, Adenocarcinoma, EGFR, matuzumab, EMD 72000, randomized, Epirubicin, cisplatin, capecitabine, Metastatic Esophago-Gastric cancer