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

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 2

Conditions: Non Small Cell Lung Carcinoma; Lung Cancer

Treatments: Drug: Matuzumab; Drug: Pemetrexed

Study type: Interventional

Funder types: Industry

Identifiers

NCT00111839

2006-000899-32 (EudraCT Number)

EMD 72000-031

Details and patient eligibility

About

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.

Enrollment: 150 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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150 participants in 3 patient groups

Pemetrexed Alone

Active Comparator group

Description:

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.

Treatment:

Drug: Pemetrexed

Pemetrexed Plus Matuzumab 800 mg per Week

Experimental group

Description:

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.

Treatment:

Drug: Pemetrexed

Drug: Matuzumab

Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks

Experimental group

Description:

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.

Treatment:

Drug: Pemetrexed

Drug: Matuzumab