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

Study Overview
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Brief Summary
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This open-label, multicenter, randomized, controlled, Phase II study is planned to answer questions about how the drug, matuzumab (EMD 72000), works and is part of an effort aimed to develop better treatment for advanced lung cancer by combining matuzumab, a monoclonal antibody, with a chemotherapy treatment, called pemetrexed.

Official Title
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Randomized, Phase II, Open-Label Controlled Study of Two Different Doses and Schedules of EMD 72000 (Matuzumab) in Combination With Pemetrexed, or Pemetrexed Alone, as Second-Line Treatment for Stage IIIB/IV Non-Small Cell Lung Cancer and Progressive Disease on or After First-Line Treatment With a Platinum in Combination With Taxanes, Gemcitabine and Vinorelbine

Conditions
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Lung Cancer, Non Small Cell Lung Carcinoma

Intervention / Treatment
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* Drug: Pemetrexed
* Drug: Matuzumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pemetrexed Alone<br>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<br>* Pemetrexed will be administered IV until PD or the occurrence of unacceptable toxicity.<br>|
| Experimental: Pemetrexed Plus Matuzumab 800 mg per Week<br>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<br>* Pemetrexed will be administered IV until PD or the occurrence of unacceptable toxicity.<br>Drug: Matuzumab<br>* Matuzumab will be administered IV until PD or the occurrence of unacceptable toxicity.<br>|
| Experimental: Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks<br>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<br>* Pemetrexed will be administered IV until PD or the occurrence of unacceptable toxicity.<br>Drug: Matuzumab<br>* Matuzumab will be administered IV until PD or the occurrence of unacceptable toxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 Outcome Measures

| Outcome Measure | 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) | 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. | Baseline up to PD or death due to any cause (up to approximately 3.5 years) | 
| 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. | From first documented objective response to PD or death due to any cause (up to approximately 3.5 years) | 
| 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). | Baseline, Cycle 2 (Cycle length = 3 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung cancer