Esophageal Cancer, Gastric Cancer
Conditions
Keywords
Esophagus, Gastric, Adenocarcinoma, EGFR, matuzumab, EMD 72000, randomized, Epirubicin, cisplatin, capecitabine, Metastatic Esophago-Gastric cancer
Brief summary
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.
Interventions
DRUGMatuzumab
Participants will receive matuzumab 800 milligrams (mg) intravenously (IV) every week, until disease progression (PD), unacceptable toxicity, death, or consent is withdrawn.
DRUGEpirubicin
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.
DRUGCisplatin
Participants will receive cisplatin 60 mg/m\^2 on Day 1 of 21-day cycle up to a maximum of 8 cycles.
DRUGCapecitabine
Participants will receive capecitabine 1250 mg/m\^2 daily in a 21-day cycles up to a maximum of 8 cycles.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response Assessed by Independent Review Committee | Baseline up to PD or death due to any cause (up to approximately 3 years) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | Baseline up to PD or death due to any cause (up to approximately 3 years) | 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. |
| Overall Survival (OS) | Baseline until death due to any cause (up to approximately 3 years) | OS was defined as the duration from randomization to death (due to any cause). OS was estimated using Kaplan-Meier analysis. |
| Matuzumab Serum Concentration | Baseline up to approximately 3 years | — |
| Duration of Objective Response Assessed by Independent Review Committee | From first documented objective response to PD or death due to any cause (up to approximately 3 years) | 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. |
| Protein Biomarkers Levels | Baseline up to approximately 3 years | — |
| Percentage of Participants With Anti-Matuzumab Antibodies | Baseline 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 | Baseline (Day 1), Post Baseline (Up to 3 Years) | 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. |
Countries
Germany, Spain, Switzerland, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Epirubicin, Cisplatin, Capecitabine (ECX)+Matuzumab Participants received matuzumab 800 mg IV every week and epirubicin 50 mg/m\^2, cisplatin 60 mg/m\^2 on Day 1 and capecitabine 1250 mg/m\^2 daily in a 21-day cycles (ECX). A maximum of 8 cycles of ECX were administered and after 8 cycles, matuzumab alone was continued until PD, unacceptable toxicity, death, or consent was withdrawn. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of epirubicin administration when these treatments were given on the same day. | 35 |
| ECX Only Participants received epirubicin 50 mg/m\^2, cisplatin 60 mg/m\^2 on Day 1 and capecitabine 1250 mg/m\^2 daily in a 21-day cycles (ECX). A maximum of 8 cycles of ECX were administered unless there was evidence of PD, or unacceptable toxicity, death occurred or consent was withdrawn. | 36 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 9 |
| Overall Study | Death | 1 | 2 |
| Overall Study | Disease Progression | 28 | 10 |
| Overall Study | Other | 3 | 15 |
| Overall Study | Randomized but Not Treated | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Epirubicin, Cisplatin, Capecitabine (ECX)+Matuzumab | ECX Only | Total |
|---|---|---|---|
| Age, Continuous | 59 years | 64 years | 62 years |
| Sex: Female, Male Female | 11 Participants | 9 Participants | 20 Participants |
| Sex: Female, Male Male | 24 Participants | 27 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 35 / 35 | 36 / 36 |
| serious Total, serious adverse events | 0 / 35 | 0 / 36 |
Outcome results
Primary
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.
Time frame: Baseline up to PD or death due to any cause (up to approximately 3 years)
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epirubicin, Cisplatin, Capecitabine (ECX)+Matuzumab | Percentage of Participants With Objective Response Assessed by Independent Review Committee | 31 percentage of participants |
| ECX Only | Percentage of Participants With Objective Response Assessed by Independent Review Committee | 58 percentage of participants |
Secondary
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.
Time frame: Baseline (Day 1), Post Baseline (Up to 3 Years)
Population: ITT population. Here, overall number of participants analyzed = participants who were evaluable for this outcome and Number analyzed = participants evaluable for specified timepoint for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Epirubicin, Cisplatin, Capecitabine (ECX)+Matuzumab | 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 | Baseline | 53.3 units on a scale | Standard Deviation 27.3 |
| Epirubicin, Cisplatin, Capecitabine (ECX)+Matuzumab | 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 | Post-Baseline | 0.0 units on a scale | Standard Deviation 28.1 |
| ECX Only | 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 | Baseline | 67.9 units on a scale | Standard Deviation 22.4 |
| ECX Only | 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 | Post-Baseline | -10.0 units on a scale | Standard Deviation 33.9 |
Secondary
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.
Time frame: From first documented objective response to PD or death due to any cause (up to approximately 3 years)
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Epirubicin, Cisplatin, Capecitabine (ECX)+Matuzumab | Duration of Objective Response Assessed by Independent Review Committee | NA months |
| ECX Only | Duration of Objective Response Assessed by Independent Review Committee | NA months |
Secondary
Matuzumab Serum Concentration
Time frame: Baseline up to approximately 3 years
Population: Data for this outcome was not collected from any of the participant; hence, no data available for reporting.
Secondary
Overall Survival (OS)
OS was defined as the duration from randomization to death (due to any cause). OS was estimated using Kaplan-Meier analysis.
Time frame: Baseline until death due to any cause (up to approximately 3 years)
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Epirubicin, Cisplatin, Capecitabine (ECX)+Matuzumab | Overall Survival (OS) | 9.4 months |
| ECX Only | Overall Survival (OS) | 12.2 months |
Secondary
Percentage of Participants With Anti-Matuzumab Antibodies
Time frame: Baseline up to approximately 3 years
Population: Data for this outcome was not collected from any of the participant; hence, no data available for reporting.
Secondary
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.
Time frame: Baseline up to PD or death due to any cause (up to approximately 3 years)
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Epirubicin, Cisplatin, Capecitabine (ECX)+Matuzumab | Progression-Free Survival | 4.8 months |
| ECX Only | Progression-Free Survival | 7.1 months |
Secondary
Protein Biomarkers Levels
Time frame: Baseline up to approximately 3 years
Population: Data for this outcome was not collected from any of the participant; hence, no data available for reporting.