Stage IIIB/IV non-small cell lung cancer and progressive disease on or after first-line treatment with a platinum analogue in combination with either taxanes, gemcitabine or vinorelbine MedDRA version: 8.1 Level: LLT Classification code 10061873
Conditions
Sponsors
EMD Pharmaceuticals, Inc. (an affiliate of Merck KGaA, Darmstadt, Germany)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent provided prior to any screening procedure 2. Male or female, =18years of age 3. Histologically or cytologically confirmed diagnosis of NSCLC 4. Demonstrated progressive disease 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 patients must have measurable disease (tumor) without clinically significant pleural effusion unless the pleural can be effectively drained prior to admission into the study. 5. A chemotherapy-free interval of at least 3 weeks between the end of first-line chemotherapy and start of study treatment 6. At least 1 measurable lesion according to the modified WHO criteria as defined in Section 7.2.2 7. Archived tissue or cytologic sample available for the determination of EGFR expression 8. ECOG performance status 0-1 9. Life expectancy >12 weeks 10. Adequate baseline organ functions, defined as follows: Serum creatinine =1.5 × upper limit of normal (ULN) In case of borderline values for serum creatinine, creatinine clearance must be =45 mL/min Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Radiotherapy or major surgery within 30 days prior to the start of study treatment 2. Prior treatment with an EGFR-directed therapy or with EGFR signal transduction inhibitors 3. Prior treatment with pemetrexed 4. Pregnant (confirmed by ß-HCG) or lactating female 5. Weight loss >10% within 12 weeks prior to the start of study treatment 6. Documented or symptomatic brain metastases or leptomeningeal disease 7. 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 8. Presence of a =Grade 2 preexisting skin disorder (except for alopecia) 9. Previous diagnosis of autoimmune disease with significant organ involvement 10. 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 11. Any significant disease that, in the Investigator’s opinion, should exclude the subject from the study 12. History of significant neurologic or psychiatric disorder (e.g., dementia, seizures, or bipolar disorder) 13. History of drug abuse within 6 months prior to the start of study treatment 14. Known conditions that require concurrent treatment with a nonpermitted drug (see Section 6.8.2 of the protocol) 15. Presence of a contraindication to the study treatment(s) according to the current Investigator’s Brochure (IB) for matuzumab and the labeling for pemetrexed 16. Known hypersensitivity to the study treatment or any of its components 17. Participation in another clinical study within 30 days prior to the start of study treatment 18. Legal incapacity or limited legal capacity
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the tumor response rate (as assessed by the Independent Review Committee [IRC]) of 2 different regimens of matuzumab in combination with pemetrexed in comparison to pemetrexed alone in subjects with Stage IIIB/IV non-small cell lung cancer (NSCLC).;Secondary Objective: The secondary objectives of this study are to determine the following: • Tumor response rate (as assessed by the Investigator) • Overall survival • Time to tumor progression • Duration of response • Safety and tolerability • Quality of life (QoL) Additional objectives of this study include evaluation of: • Human antihumanized antibody (HAHA) • Pharmacokinetics (PK) of matuzumab • Epidermal growth factor receptor (EGFR) mutation analysis and association of EGFR mutations with tumor response • EGFR detectability by IHC and its association with tumor resonse;Primary end point(s): Tumor response rate (as determined by the IRC). Tumor assessments will be done by CT or MRI scanning obtained at screening and every 6 weeks (or sooner if medically indicated). Response assessments will be conducted according to modified WHO criteria. | — |
Countries
Austria, Germany
Outcome results
None listed