Stage IIIB/IV non-small cell lung cancer and progressive disease after first-line treatment with a platinum analogue in comination with taxanes, gemcitabine, or vinorelbine MedDRA version: 8.1 Level: LLT Classification code 10061873
Conditions
Sponsors
Merck KGaA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent / written informed consent for analysis of biomarker is optional and not required for participation in the main study 2. Male or female; Age =18 years 3. Histological or cytological confirmed diagnosis of advanced NSCLC 4. Radiographic demonstrated progression during or after treatment and have Stage IIIB/IV disease initially or at time of enrollment. The subject must have received at least 1 prior therapy for NSCLC. The first line treatment must have consisted of a platinum analogue in combination with taxanes, gemcitabine, or vinorelbine 5. At least 1 bidimensional measurable lesion according to the modified WHO criteria 6. ECOG performance status of 0, 1, or 2 7. Adequate baseline hematologic values within 1 week prior to start of active treatment defined as follows: •Absolute neutrophil count (ANC) =1500 cells/µL •Platelet count =100,000 cells/µL •Hemoglobin =9.0 g/dL 8. Adequate organ functions within 1 week prior to start of active treatment defined as follows: •Serum creatinine =1.5 x upper limit of normal (ULN) •Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Prior treatment with an investigational or marketed inhibitor of the EGFR pathway 2. Subject received systemic chemotherapy, radiotherapy, or investigational treatment (on or off a clinical study) within 30 days prior to treatment 3. Pregnant (confirmed by ß -HCG) or lactating female 4. Presence of a =grade 2 preexisting skin disorder (except for alopecia) 5. Weight loss >10% within 12 weeks prior to the start of study treatment 6. History of serious systemic disease, including myocardial infarction within the last 6 months, uncontrolled hypertension (blood pressure >150/100 mmHg on medication), unstable angina, New York Heart Association (NYHA) grade 2 or greater congestive heart failure (CHF), unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), clinically significant peripheral vascular disease or any current grade 3 or 4 cardiovascular disorder despite treatment 7. Documented history of symptomatic brain metastases 8. Previous diagnosis of autoimmune disease with significant organ involvement 9. History of drug-related acute infusion reaction 10. Inability to take oral medication or requirement for intravenous (IV) alimentation or total parenteral nutrition with lipids, or prior surgical procedures affecting absorption 11. Presence of another invasive cancer within 5 years prior to start of active treatment, except for adequately treated basal cell skin cancer, or in situ carcinoma of the cervix 12. History of significant neurologic or psychiatric disorder (e.g., dementia, seizures, or bipolar disorder) that may impair the subject's understanding of the Informed Consent Form or ability to comply with study requirements 13. History of alcohol or substance abuse as defined by the Diagnostic and Statistical Manual (DSM-IV) criteria, within 6 months prior to start of study treatment 14. Known conditions that require concurrent treatment with a nonpermitted drug 15. Presence of a contraindication to erlotinib according to the labeling for erlotinib 16. Known hypersensitivity to the study treatment or any of its components 17. Any significant disease that, in the Investigator’s opinion, should exclude the subject from the study 18. Legal incapacity or limited legal capacity
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective Phase I: •To determine the safety of matuzumab in combination with erlotinib in up to 5 different dose cohorts. Primary Objective Phase II: •To determine the tumor response rate (RR; defined as complete response [CR] plus partial response [PR]) of matuzumab in combination with erlotinib, at a single dose chosen from phase I, according to the modified World Health Organization (WHO) criteria as assessed by an Independent Review Committee (IRC).;Secondary Objective: Secondary Objectives Phases I and II: •To determine the rate of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) overall and in each cohort in phase I, For subjects in the dose cohort chosen for phase II, rates will also be assessed by the IRC as part of the phase II portion of the study •To determine time to progression (TTP) for subjects receiving the phase II dose regimen •To determine overall survival (OS) for subjects receiving the phase II dose regimen •To determine duration of response for subjects receiving the phase II dose regimen •To determine the pharmacokinetic (PK) profile of matuzumab in combination with erlotinib in all dose cohorts in the phase I portion of the study •To determine human anti-humanized antibody (HAHA) levels in serum •To obtain most recent archived tumor tissue for determination of EGFR expression and optional biomarkers •To determine overall safety;Primary end point(s): Phase I: Determination of the safety of Matuzumab in combination with Erlotinib in up to 5 dose cohorts Phase II: 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 of medically indicated). Response assessments will be conducted according to modified WHO criteria. | — |
Countries
Germany
Outcome results
None listed