Effects of Matuzumab in Combination With Pemetrexed for t... | NCT00111839

NCT00111839

ID	Type	Description	Link
2006-000899-32	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Pemetrexed Alone	Active Comparator	Participants will receive 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.	Drug: Pemetrexed
Pemetrexed Plus Matuzumab 800 mg per Week	Experimental	Participants will receive pemetrexed 50 mg/m^2 IV infusion every 3 weeks in combination with matuzumab 800 milligrams (mg) IV infusion once every week. Treatment will continue until PD or the occurrence of unacceptable toxicity.	Drug: Pemetrexed Drug: Matuzumab
Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks	Experimental	Participants will receive pemetrexed 50 mg/m^2 IV infusion every 3 weeks in combination with matuzumab 1600 mg IV infusion every 3 weeks. Treatment will continue until PD or the occurrence of unacceptable toxicity.	Drug: Pemetrexed Drug: Matuzumab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Pemetrexed	Drug	Pemetrexed will be administered IV until PD or the occurrence of unacceptable toxicity.	Pemetrexed Alone Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number 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. 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.	Baseline up to PD or death due to any cause (up to approximately 2 years)

Secondary Outcomes

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

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Written informed consent provided prior to any screening procedure
Male or female, greater than (>) 18 years of age
Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)
Demonstrated PD on or after first-line chemotherapy for Stage IIIB/IV disease. The first-line therapy must consist of platinum-based regimens in combination with taxanes, gemcitabine or vinorelbine. Stage IIIB/IV participants must have measurable disease (tumor) without clinically significant pleural effusion unless the pleural effusion can be effectively drained prior to admission into the study
A chemotherapy-free interval of at least 3 weeks between the end of first-line chemotherapy and start of study treatment
At least 1 measurable lesion according to the modified World Health Organization (WHO) criteria
Archived tissue or cytologic sample available for the determination of epidermal growth factor receptor (EGFR) expression
Eastern cooperative oncology group (ECOG) performance status 0-1
Life expectancy >12 weeks
Adequate baseline organ functions, defined as: Serum creatinine less than or equal to (≤)1.5*upper limit of normal (ULN). In case of borderline values for serum creatinine, creatinine clearance must be greater than or equal to (≥) 45 millimeters per minute (mL/min); Total bilirubin <1.5*ULN; Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5*ULN (participants with liver metastases should have ALT/AST <5*ULN.); Absolute neutrophil count ≥1500per cubic millimeter(mm^3); Platelet count ≥100000/mm^3; Hemoglobin level ≥10 grams per deciliter
If procreative potential (male or female), willingness to use effective contraceptive methods for the duration of treatment and continuing for 2 months after the last dose. Participants of procreative potential are defined as any fertile male, or any female who has experienced menarche and who is not postmenopausal (defined as age-related amenorrhea ≥12 months) or who has not undergone successful surgical sterilization (hysterectomy or bilateral oophorectomy)

Exclusion Criteria:

Radiotherapy or major surgery within 30 days prior to the start of study treatment
Prior treatment with an EGFR-directed therapy or with EGFR signal transduction inhibitors
Prior treatment with pemetrexed
Pregnant (confirmed by beta-human chorionic gonadotropin [β-HCG]) or lactating female
Weight loss >10% within 12 weeks prior to the start of study treatment
Documented or symptomatic brain metastases or leptomeningeal disease
Myocardial infarction within 6 months prior to the start of study treatment, uncontrolled congestive heart failure, or any current New York Heart Association Grade III or IV cardiovascular disorder despite treatment
Presence of a Grade ≥2 preexisting skin disorder (except for alopecia)
Previous diagnosis of autoimmune disease with significant organ involvement
Concurrent malignancies or invasive carcinomas diagnosed within the past 5 years, except for adequately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix
Any significant disease that, in the Investigator's opinion, should exclude the participant from the study
History of significant neurologic or psychiatric disorder (for example, dementia, seizures, or bipolar disorder)
History of drug abuse within 6 months prior to the start of study treatment
Known conditions that require concurrent treatment with a nonpermitted drug
Presence of a contraindication to the study treatment(s) according to the current Investigator's Brochure (IB) for matuzumab and the labeling for pemetrexed
Known hypersensitivity to the study treatment or any of its components
Participation in another clinical study within 30 days prior to the start of study treatment

Contacts/Locations Module

Name	Affiliation	Role
Medical Responsible	EMD Serono Inc., an affiliate of Merck KGaA, Darmstadt, Germany	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Arizona Clinical Research Center		Tucson	Arizona	85715	United States
University of Arkansas, Arkansas Cancer Research Center

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
20978446	Result	Schiller JH, von Pawel J, Schutt 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.

Label	URL
EudraCT results summary synopsis	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	Pemetrexed Plus Matuzumab 800 mg Per Week

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Pemetrexed Plus Matuzumab 800 mg per Week

Intent to treat (ITT) population included all randomized participants who received at least one infusion of study treatment.

Arm/Group Information

ID	Title	Description
BG000	Pemetrexed Alone	Participants received pemetrexed 50 mg/m^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.
BG001	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.
BG002	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.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	OG0002(1 to 14) OG0018(7 to 29) OG0021(0 to 11)

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.

ITT population.

Posted

Median

95% Confidence Interval

months

Baseline up to PD or death due to any cause (up to approximately 3.5 years)

ID	Title	Description
OG000	Pemetrexed Alone	Participants received pemetrexed 50 mg/m^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.
OG001	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.
OG002	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.

Secondary

Progression-Free Survival (PFS)

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.

ITT population.

Posted

Median

95% Confidence Interval

months

Baseline up to PD or death due to any cause (up to approximately 3.5 years)

ID	Title	Description
OG000	Pemetrexed Alone	Participants received pemetrexed 50 mg/m^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.
OG001	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.
OG002	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.

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 (>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.

ITT population.

Posted

Median

95% Confidence Interval

months

From first documented objective response to PD or death due to any cause (up to approximately 3.5 years)

ID	Title	Description
OG000	Pemetrexed Alone	Participants received pemetrexed 50 mg/m^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.
OG001	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.

Secondary

Change From Baseline to Cycle 2 in Global Quality of Life (QoL), as Assessed Using Lung Cancer Symptom Scale (LCSS)

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).

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

Posted

Mean

Standard Deviation

units on a scale

Baseline, Cycle 2 (Cycle length = 3 weeks)

ID	Title	Description
OG000	Pemetrexed Alone	Participants received pemetrexed 50 mg/m^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.
OG001	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.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pemetrexed Alone	Participants received pemetrexed 50 mg/m^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity.	9	50	8	50
EG001	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.	5	51	20	51
EG002	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.	11	47	18	47

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 9.0	Non-systematic Assessment		EG0001 affected50 at risk EG0011 affected51 at risk EG0023 affected47 at risk
	General disorders	MedDRA 9.0	Non-systematic Assessment		EG0008 affected50 at risk EG0014 affected51 at risk EG0028 affected47 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Neutropenia	Blood and lymphatic system disorders	MedDRA 9.0	Non-systematic Assessment	EG0006 affected50 at risk EG00111 affected51 at risk EG0027 affected47 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 9.0	Non-systematic Assessment	EG0000 affected50 at risk EG0011 affected51 at risk EG0025 affected47 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 9.0	Non-systematic Assessment	EG0001 affected50 at risk EG0013 affected51 at risk EG0023 affected47 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 9.0	Non-systematic Assessment	EG0000 affected50 at risk EG0011 affected51 at risk EG0023 affected47 at risk
Fatigue	General disorders	MedDRA 9.0	Non-systematic Assessment	EG0001 affected50 at risk EG0014 affected51 at risk EG0021 affected47 at risk

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.

Certain Agreements

ID	Term
D008175	Lung Neoplasms
D002289	Carcinoma, Non-Small-Cell Lung

Ancestor Terms

ID	Term
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms

ID	Term
D000068437	Pemetrexed
C520777	matuzumab

Ancestor Terms

ID	Term
D006147	Guanine
D007042	Hypoxanthines
D011688	Purinones
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D005971	Glutamates
D024342	Amino Acids, Acidic
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D000600	Amino Acids, Dicarboxylic