Trial Outcomes & Findings for Effects of Matuzumab in Combination With Pemetrexed for the Treatment of Advanced Lung Cancer (NCT NCT00111839)
NCT ID: NCT00111839
Last Updated: 2018-04-06
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. Complete response: 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
150 participants
Primary outcome timeframe
Baseline up to PD or death due to any cause (up to approximately 2 years)
Results posted on
2018-04-06
Participant Flow
Participant milestones
| Measure |
Pemetrexed Alone
Participants received pemetrexed 50 milligrams per square meter (mg/m\^2) intravenous (IV) infusion every 3 weeks until disease progression (PD) or the occurrence of unacceptable toxicity.
|
Pemetrexed Plus Matuzumab 800 mg Per Week
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 800 mg IV infusion once every week. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity.
|
Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 1600 mg IV infusion every 3 weeks. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity.
|
|---|---|---|---|
|
Overall Study
STARTED
|
50
|
51
|
49
|
|
Overall Study
Treated
|
50
|
51
|
47
|
|
Overall Study
COMPLETED
|
2
|
5
|
0
|
|
Overall Study
NOT COMPLETED
|
48
|
46
|
49
|
Reasons for withdrawal
| Measure |
Pemetrexed Alone
Participants received pemetrexed 50 milligrams per square meter (mg/m\^2) intravenous (IV) infusion every 3 weeks until disease progression (PD) or the occurrence of unacceptable toxicity.
|
Pemetrexed Plus Matuzumab 800 mg Per Week
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 800 mg IV infusion once every week. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity.
|
Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 1600 mg IV infusion every 3 weeks. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity.
|
|---|---|---|---|
|
Overall Study
Disease Progression
|
30
|
33
|
33
|
|
Overall Study
Adverse Event
|
5
|
3
|
1
|
|
Overall Study
Protocol Violation
|
2
|
4
|
2
|
|
Overall Study
Death
|
1
|
1
|
6
|
|
Overall Study
Withdrawal by Subject
|
2
|
2
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
|
Overall Study
Logistical Constraint
|
1
|
0
|
0
|
|
Overall Study
Other
|
6
|
3
|
3
|
|
Overall Study
Randomized but Not Treated
|
0
|
0
|
2
|
Baseline Characteristics
Effects of Matuzumab in Combination With Pemetrexed for the Treatment of Advanced Lung Cancer
Baseline characteristics by cohort
| Measure |
Pemetrexed Alone
n=50 Participants
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.
|
Pemetrexed Plus Matuzumab 800 mg Per Week
n=51 Participants
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 800 mg IV infusion once every week. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity.
|
Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
n=47 Participants
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 1600 mg IV infusion every 3 weeks. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity.
|
Total
n=148 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
61 years
n=99 Participants
|
62 years
n=107 Participants
|
63 years
n=206 Participants
|
62 years
n=7 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
53 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
33 Participants
n=99 Participants
|
35 Participants
n=107 Participants
|
27 Participants
n=206 Participants
|
95 Participants
n=7 Participants
|
PRIMARY outcome
Timeframe: Baseline up to PD or death due to any cause (up to approximately 2 years)Population: ITT population.
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. Complete response: 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.
Outcome measures
| Measure |
Pemetrexed Alone
n=50 Participants
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.
|
Pemetrexed Plus Matuzumab 800 mg Per Week
n=51 Participants
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 800 mg IV infusion once every week. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity.
|
Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
n=47 Participants
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 1600 mg IV infusion every 3 weeks. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity.
|
|---|---|---|---|
|
Number of Participants With Objective Response Assessed by Independent Review Committee
|
2 participants
Interval 1.0 to 14.0
|
8 participants
Interval 7.0 to 29.0
|
1 participants
Interval 0.0 to 11.0
|
SECONDARY outcome
Timeframe: Baseline up to PD or death due to any cause (up to approximately 3.5 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
| Measure |
Pemetrexed Alone
n=50 Participants
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.
|
Pemetrexed Plus Matuzumab 800 mg Per Week
n=51 Participants
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 800 mg IV infusion once every week. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity.
|
Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
n=47 Participants
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 1600 mg IV infusion every 3 weeks. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity.
|
|---|---|---|---|
|
Overall Survival (OS)
|
7.9 months
Interval 7.2 to 9.9
|
12.4 months
Interval 8.8 to
The upper limit of 95% confidence interval (CI) could not be estimated due to insufficient number of participants with event (death).
|
5.9 months
Interval 3.6 to 7.2
|
SECONDARY outcome
Timeframe: Baseline up to PD or death due to any cause (up to approximately 3.5 years)Population: ITT population.
PFS was defined as the time from randomization to the first documentation of disease progression (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
| Measure |
Pemetrexed Alone
n=50 Participants
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.
|
Pemetrexed Plus Matuzumab 800 mg Per Week
n=51 Participants
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 800 mg IV infusion once every week. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity.
|
Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
n=47 Participants
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 1600 mg IV infusion every 3 weeks. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity.
|
|---|---|---|---|
|
Progression-Free Survival (PFS)
|
2.7 months
Interval 1.6 to 4.4
|
2.3 months
Interval 1.5 to 3.8
|
2.5 months
Interval 1.4 to 2.9
|
SECONDARY outcome
Timeframe: From first documented objective response to PD or death due to any cause (up to approximately 3.5 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 (\>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
| Measure |
Pemetrexed Alone
n=50 Participants
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.
|
Pemetrexed Plus Matuzumab 800 mg Per Week
n=51 Participants
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 800 mg IV infusion once every week. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity.
|
Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
n=47 Participants
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 1600 mg IV infusion every 3 weeks. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity.
|
|---|---|---|---|
|
Duration of Objective Response Assessed by Independent Review Committee
|
NA months
Data could not be estimated due to higher number (\>50%) of censored participants.
|
NA months
Data could not be estimated due to higher number (\>50%) of censored participants.
|
NA months
Data could not be estimated due to higher number (\>50%) of censored participants.
|
SECONDARY outcome
Timeframe: Baseline, Cycle 2 (Cycle length = 3 weeks)Population: ITT population. Here, overall number of participants analyzed = participants with available data for this outcome; number analyzed = participants with available data at specified timepoint.
The LCSS consisted of 9 items: 6 items focused on lung cancer symptoms (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain\] and 3 items were global items (symptom distress, interference with activity level, and global QoL). The global QoL item scores are reported here. The total global QoL item score ranged from 0 (worse QoL) to 100 (best QoL).
Outcome measures
| Measure |
Pemetrexed Alone
n=45 Participants
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.
|
Pemetrexed Plus Matuzumab 800 mg Per Week
n=46 Participants
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 800 mg IV infusion once every week. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity.
|
Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
n=44 Participants
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 1600 mg IV infusion every 3 weeks. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity.
|
|---|---|---|---|
|
Change From Baseline to Cycle 2 in Global Quality of Life (QoL), as Assessed Using Lung Cancer Symptom Scale (LCSS)
Baseline
|
35.9 units on a scale
Standard Deviation 26.0
|
31.1 units on a scale
Standard Deviation 25.8
|
35.8 units on a scale
Standard Deviation 27.5
|
|
Change From Baseline to Cycle 2 in Global Quality of Life (QoL), as Assessed Using Lung Cancer Symptom Scale (LCSS)
Change at Cycle 2
|
3.5 units on a scale
Standard Deviation 17.2
|
0.8 units on a scale
Standard Deviation 19.9
|
15.7 units on a scale
Standard Deviation 30.7
|
Adverse Events
Pemetrexed Alone
Serious events: 9 serious events
Other events: 8 other events
Deaths: 0 deaths
Pemetrexed Plus Matuzumab 800 mg Per Week
Serious events: 5 serious events
Other events: 20 other events
Deaths: 0 deaths
Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
Serious events: 11 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pemetrexed Alone
n=50 participants at risk
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.
|
Pemetrexed Plus Matuzumab 800 mg Per Week
n=51 participants at risk
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 800 mg IV infusion once every week. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity.
|
Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
n=47 participants at risk
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 1600 mg IV infusion every 3 weeks. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.0%
1/50
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
2.0%
1/51
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
6.4%
3/47
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
|
General disorders
|
16.0%
8/50
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
7.8%
4/51
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
17.0%
8/47
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
Other adverse events
| Measure |
Pemetrexed Alone
n=50 participants at risk
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.
|
Pemetrexed Plus Matuzumab 800 mg Per Week
n=51 participants at risk
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 800 mg IV infusion once every week. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity.
|
Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
n=47 participants at risk
Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 1600 mg IV infusion every 3 weeks. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
12.0%
6/50
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
21.6%
11/51
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
14.9%
7/47
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/50
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
2.0%
1/51
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
10.6%
5/47
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
|
Blood and lymphatic system disorders
Leukopenia
|
2.0%
1/50
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
5.9%
3/51
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
6.4%
3/47
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/50
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
2.0%
1/51
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
6.4%
3/47
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
|
General disorders
Fatigue
|
2.0%
1/50
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
7.8%
4/51
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
2.1%
1/47
Among SAEs, data for total # affected by any SAE and total # affected by febrile neutropenia are only available. Due diligence was done and all potential information sources have been exhausted; no further information could be retrieved. Hence, for other participants preferred term "Not Available" and System Organ Class "General Disorders" is used.
|
Additional Information
Merck KGaA Communication Center
Merck Serono, a division of Merck KGaA
Phone: 496151725200
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place