Trial Outcomes & Findings for Matuzumab Treatment With Epirubicin, Cisplatin and Capecitabine (ECX) in Esophago-Gastric Cancer (NCT NCT00215644)

Last Updated: 2018-11-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

72 participants

Primary outcome timeframe

Baseline up to PD or death due to any cause (up to approximately 3 years)

Results posted on

2018-11-02

Participant Flow

Participant milestones

Participant milestones
Measure	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administered and after 8 cycles, matuzumab alone was continued until PD, unacceptable toxicity, death, or consent was withdrawn.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.	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of ECX were administered unless there was evidence of PD, or unacceptable toxicity, death occurred or consent was withdrawn.
Overall Study STARTED	36	36
Overall Study Treated	35	36
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	36	36

Reasons for withdrawal

Reasons for withdrawal
Measure	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administered and after 8 cycles, matuzumab alone was continued until PD, unacceptable toxicity, death, or consent was withdrawn.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.	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.
Overall Study Disease Progression	28	10
Overall Study Adverse Event	2	9
Overall Study Death	1	2
Overall Study Withdrawal by Subject	1	0
Overall Study Other	3	15
Overall Study Randomized but Not Treated	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Epirubicin, Cisplatin, Capecitabine (ECX)+Matuzumab n=35 Participants 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.	ECX Only n=36 Participants 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.	Total n=71 Participants Total of all reporting groups
Age, Continuous	59 years n=5 Participants	64 years n=7 Participants	62 years n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	27 Participants n=7 Participants	51 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to PD or death due to any cause (up to approximately 3 years)

Population: ITT population.

Outcome measures

Outcome measures
Measure	Epirubicin, Cisplatin, Capecitabine (ECX)+Matuzumab n=35 Participants 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.	ECX Only n=36 Participants 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.
Percentage of Participants With Objective Response Assessed by Independent Review Committee	31 percentage of participants Interval 17.0 to 49.0	58 percentage of participants Interval 41.0 to 74.0

SECONDARY outcome

Timeframe: From first documented objective response to PD or death due to any cause (up to approximately 3 years)

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	Epirubicin, Cisplatin, Capecitabine (ECX)+Matuzumab n=35 Participants 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.	ECX Only n=36 Participants 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.
Duration of Objective Response Assessed by Independent Review Committee	NA months Data could not be estimated because less than 50% of participants were reported with objective response.	NA months Data could not be estimated because less than 50% of participants were reported with objective response.

SECONDARY outcome

Timeframe: Baseline up to PD or death due to any cause (up to approximately 3 years)

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	Epirubicin, Cisplatin, Capecitabine (ECX)+Matuzumab n=35 Participants 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.	ECX Only n=36 Participants 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.
Progression-Free Survival	4.8 months Interval 2.9 to 8.1	7.1 months Interval 4.4 to 8.5

SECONDARY outcome

Timeframe: Baseline until death due to any cause (up to approximately 3 years)

Population: ITT population.

OS was defined as the duration from randomization to death (due to any cause). OS was estimated using Kaplan-Meier analysis.

Outcome measures

Outcome measures
Measure	Epirubicin, Cisplatin, Capecitabine (ECX)+Matuzumab n=35 Participants 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.	ECX Only n=36 Participants 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.
Overall Survival (OS)	9.4 months Interval 7.5 to 16.2	12.2 months Interval 9.8 to 13.8

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Epirubicin, Cisplatin, Capecitabine (ECX)+Matuzumab n=30 Participants 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.	ECX Only n=33 Participants 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.
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	67.9 units on a scale Standard Deviation 22.4
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	-10.0 units on a scale Standard Deviation 33.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

Adverse Events

Epirubicin, Cisplatin, Capecitabine (ECX)+Matuzumab

Serious events: 0 serious events

Other events: 35 other events

Deaths: 0 deaths

ECX Only

Serious events: 0 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Merck KGaA Communication Center,

Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

Phone: 496151725200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Epirubicin, Cisplatin, Capecitabine (ECX)+Matuzumab n=35 participants at risk 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.	ECX Only n=36 participants at risk 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.
Blood and lymphatic system disorders Neutropenia	37.1% 13/35 Only selected AEs were collected and reported.	33.3% 12/36 Only selected AEs were collected and reported.
Blood and lymphatic system disorders Anaemia	5.7% 2/35 Only selected AEs were collected and reported.	5.6% 2/36 Only selected AEs were collected and reported.
Blood and lymphatic system disorders Febrile neutropenia	2.9% 1/35 Only selected AEs were collected and reported.	5.6% 2/36 Only selected AEs were collected and reported.
General disorders Fatigue/lethargy	20.0% 7/35 Only selected AEs were collected and reported.	13.9% 5/36 Only selected AEs were collected and reported.
Gastrointestinal disorders Nausea	11.4% 4/35 Only selected AEs were collected and reported.	2.8% 1/36 Only selected AEs were collected and reported.
Gastrointestinal disorders Diarrhoea	5.7% 2/35 Only selected AEs were collected and reported.	5.6% 2/36 Only selected AEs were collected and reported.
Skin and subcutaneous tissue disorders Skin disorders	65.7% 23/35 Only selected AEs were collected and reported.	30.6% 11/36 Only selected AEs were collected and reported.
Metabolism and nutrition disorders Dehydration	8.6% 3/35 Only selected AEs were collected and reported.	2.8% 1/36 Only selected AEs were collected and reported.
Skin and subcutaneous tissue disorders Palmar plantar erythrodysaesthesia	5.7% 2/35 Only selected AEs were collected and reported.	8.3% 3/36 Only selected AEs were collected and reported.
Vascular disorders Pulmonary embolism	8.6% 3/35 Only selected AEs were collected and reported.	2.8% 1/36 Only selected AEs were collected and reported.
Infections and infestations Infection	2.9% 1/35 Only selected AEs were collected and reported.	5.6% 2/36 Only selected AEs were collected and reported.
Investigations Hypokalaemia	5.7% 2/35 Only selected AEs were collected and reported.	2.8% 1/36 Only selected AEs were collected and reported.
Cardiac disorders Myocardial infarction	2.9% 1/35 Only selected AEs were collected and reported.	5.6% 2/36 Only selected AEs were collected and reported.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/35 Only selected AEs were collected and reported.	5.6% 2/36 Only selected AEs were collected and reported.
Nervous system disorders Syncope	5.7% 2/35 Only selected AEs were collected and reported.	0.00% 0/36 Only selected AEs were collected and reported.