Effects of Matuzumab in Combination With Pemetrexed for the Treatment of Advanced Lung Cancer

• ClinicalTrials.gov Identifier: NCT00111839
• Recruitment Status: Completed
• First Posted: May 27, 2005
• Results First Posted: April 6, 2018
• Last Update Posted: April 6, 2018
• Sponsor: EMD Serono
• Information provided by (Responsible Party): EMD Serono

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Lung Cancer; Non Small Cell Lung Carcinoma
• Interventions: Drug: Pemetrexed; Drug: Matuzumab
• Enrollment: 150

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Pemetrexed Alone	Pemetrexed Plus Matuzumab 800 mg Per Week	Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
Arm/Group Description	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.	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.	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.
Period Title: Overall Study
Started	50	51	49
Treated	50	51	47
Completed	2	5	0
Not Completed	48	46	49
Reason Not Completed
Disease Progression	30	33	33
Adverse Event	5	3	1
Protocol Violation	2	4	2
Death	1	1	6
Withdrawal by Subject	2	2	2
Lost to Follow-up	1	0	0
Logistical Constraint	1	0	0
Other	6	3	3
Randomized but Not Treated	0	0	2

Baseline Characteristics

Arm/Group Title		Pemetrexed Alone	Pemetrexed Plus Matuzumab 800 mg Per Week	Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks	Total
Arm/Group Description		Participants received pemetrexed 50 mg/m^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.	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.	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 of all reporting groups
Overall Number of Baseline Participants		50	51	47	148
Baseline Analysis Population Description		Intent to treat (ITT) population included all randomized participants who received at least one infusion of study treatment.
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	50 participants	51 participants	47 participants	148 participants
		61; (37 to 83)	62; (48 to 81)	63; (46 to 78)	62; (37 to 83)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	50 participants	51 participants	47 participants	148 participants
	Female	17 34.0%	16 31.4%	20 42.6%	53 35.8%
	Male	33 66.0%	35 68.6%	27 57.4%	95 64.2%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Objective Response Assessed by Independent Review Committee
Description	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.
Time Frame	Baseline up to PD or death due to any cause (up to approximately 2 years)

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Pemetrexed Alone	Pemetrexed Plus Matuzumab 800 mg Per Week	Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
Arm/Group Description:	Participants received pemetrexed 50 mg/m^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.	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.	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 Number of Participants Analyzed	50	51	47
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: participants
	2; (1 to 14)	8; (7 to 29)	1; (0 to 11)

2. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the duration from randomization to death (due to any cause). OS was estimated using Kaplan-Meier analysis.
Time Frame	Baseline up to PD or death due to any cause (up to approximately 3.5 years)

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Pemetrexed Alone	Pemetrexed Plus Matuzumab 800 mg Per Week	Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
Arm/Group Description:	Participants received pemetrexed 50 mg/m^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.	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.	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 Number of Participants Analyzed	50	51	47
Median (95% Confidence Interval); Unit of Measure: months
	7.9; (7.2 to 9.9)	12.4 [1]; (8.8 to NA)	5.9; (3.6 to 7.2)

[1]

The upper limit of 95% confidence interval (CI) could not be estimated due to insufficient number of participants with event (death).

3. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	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.
Time Frame	Baseline up to PD or death due to any cause (up to approximately 3.5 years)

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Pemetrexed Alone	Pemetrexed Plus Matuzumab 800 mg Per Week	Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
Arm/Group Description:	Participants received pemetrexed 50 mg/m^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.	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.	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 Number of Participants Analyzed	50	51	47
Median (95% Confidence Interval); Unit of Measure: months
	2.7; (1.6 to 4.4)	2.3; (1.5 to 3.8)	2.5; (1.4 to 2.9)

4. Secondary Outcome

Title	Duration of Objective Response Assessed by Independent Review Committee
Description	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.
Time Frame	From first documented objective response to PD or death due to any cause (up to approximately 3.5 years)

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Pemetrexed Alone	Pemetrexed Plus Matuzumab 800 mg Per Week	Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
Arm/Group Description:	Participants received pemetrexed 50 mg/m^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.	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.	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 Number of Participants Analyzed	50	51	47
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

Data could not be estimated due to higher number (>50%) of censored participants.

5. Secondary Outcome

Title	Change From Baseline to Cycle 2 in Global Quality of Life (QoL), as Assessed Using Lung Cancer Symptom Scale (LCSS)
Description	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).
Time Frame	Baseline, Cycle 2 (Cycle length = 3 weeks)

Outcome Measure Data

Analysis Population Description

ITT population. Here, overall number of participants analyzed = participants with available data for this outcome; number analyzed = participants with available data at specified timepoint.

Arm/Group Title		Pemetrexed Alone	Pemetrexed Plus Matuzumab 800 mg Per Week	Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
Arm/Group Description:		Participants received pemetrexed 50 mg/m^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.	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.	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 Number of Participants Analyzed		45	46	44
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	Number Analyzed	45 participants	46 participants	44 participants
		35.9 (26.0)	31.1 (25.8)	35.8 (27.5)
Change at Cycle 2	Number Analyzed	26 participants	25 participants	24 participants
		3.5 (17.2)	0.8 (19.9)	15.7 (30.7)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	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.
Arm/Group Title	Pemetrexed Alone	Pemetrexed Plus Matuzumab 800 mg Per Week	Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
Arm/Group Description	Participants received pemetrexed 50 mg/m^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.	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.	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.
All-Cause Mortality
	Pemetrexed Alone	Pemetrexed Plus Matuzumab 800 mg Per Week	Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events
	Pemetrexed Alone	Pemetrexed Plus Matuzumab 800 mg Per Week	Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	9/50 (18.00%)	5/51 (9.80%)	11/47 (23.40%)
Blood and lymphatic system disorders
Febrile neutropenia * 1	1/50 (2.00%)	1/51 (1.96%)	3/47 (6.38%)
General disorders
* 1	8/50 (16.00%)	4/51 (7.84%)	8/47 (17.02%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 9.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Pemetrexed Alone	Pemetrexed Plus Matuzumab 800 mg Per Week	Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	8/50 (16.00%)	20/51 (39.22%)	18/47 (38.30%)
Blood and lymphatic system disorders
Neutropenia * 1	6/50 (12.00%)	11/51 (21.57%)	7/47 (14.89%)
Lymphopenia * 1	0/50 (0.00%)	1/51 (1.96%)	5/47 (10.64%)
Leukopenia * 1	1/50 (2.00%)	3/51 (5.88%)	3/47 (6.38%)
Thrombocytopenia * 1	0/50 (0.00%)	1/51 (1.96%)	3/47 (6.38%)
General disorders
Fatigue * 1	1/50 (2.00%)	4/51 (7.84%)	1/47 (2.13%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 9.0

Limitations and Caveats

For serious adverse events (SAEs), due diligence was done and all potential information sources have been exhausted, no further information could be retrieved apart from what is currently reported.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Merck KGaA Communication Center
• Organization: Merck Serono, a division of Merck KGaA
• Phone: 496151725200
• EMail: service@merckgroup.com

Publications of Results:

Schiller JH, von Pawel J, Schütt P, Ansari RH, Thomas M, Saleh M, McCroskey RD, Pfeifer W, Marsland TA, Kloecker GH, Sebastian M, Pirker R, Kurek R, Beadman C, Socinski MA. Pemetrexed with or without matuzumab as second-line treatment for patients with stage IIIB/IV non-small cell lung cancer. J Thorac Oncol. 2010 Dec;5(12):1977-85. doi: 10.1097/JTO.0b013e3181f4a5c9.

• Responsible Party: EMD Serono
• ClinicalTrials.gov Identifier: NCT00111839
• Other Study ID Numbers: EMD 72000-031; 2006-000899-32 ( EudraCT Number )
• First Submitted: May 26, 2005
• First Posted: May 27, 2005
• Results First Submitted: August 24, 2017
• Results First Posted: April 6, 2018
• Last Update Posted: April 6, 2018