This 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.
Pemetrexed is commercially available and has been approved for treatment of locally advanced
or metastatic non-small cell lung cancer that could not be successfully treated with other
chemotherapy.
The study aims to examine how non-small cell lung cancer (NSCLC) responds to matuzumab in
combination with pemetrexed, as compared with giving pemetrexed alone. The study also aims
to examine how safe and effective matuzumab is and for how long it stays in the body
(pharmacokinetics). Matuzumab is an experimental treatment which is currently only available
for research studies.
Inclusion Criteria:
- Written informed consent provided prior to any screening procedure
- Male or female,> 18 years of age
- Histologically or cytologically confirmed diagnosis of non-small cell lung cancer
- 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/IV patients must have measurable
disease (tumor) without clinically significant pleural 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 WHO criteria
- Archived tissue or cytologic sample available for the determination of EGFR
expression
- ECOG performance status 0-1
- Life expectancy >12 weeks
- 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 <1. 5 × ULN; *Alanine aminotransferase
(ALT)/aspartate aminotransferase (AST) ≤2. 5 × ULN (Subjects with liver metastases
should have ALT/AST <5 × ULN.); *Absolute neutrophil count ≥1500/mm3; *Platelet count
≥100,000/mm3; *Hemoglobin level ≥10 g/dL11
- 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.
Subjects 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 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
subject from the study
- History of significant neurologic or psychiatric disorder (e. g., 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
Research Site, Wien, Austria
Research Site, Linz, Austria
Research Site, Salzburg, Austria
Research Site, Wels, Austria
Research Site, Heidelberg, Germany
Research Site, Köln, Germany
Research Site, Freiburg, Germany
Research Site, Essen, Germany
Research Site, Göttingen, Germany
Research Site, München, Germany
Research Site, Hamburg, Germany
Research Site, Mainz, Germany
Research Site, Grosshansdorf, Germany
Research Site, Halle /Saale, Germany
Research Site, Gauting, Germany
Research Site, Recklinghausen, Germany
Arizona Clinical Research Center, Tucson, Arizona 85715, United States
University of Arkansas, Arkansas Cancer Research Center, Little Rock, Arkansas 72205, United States
University of Southern California/Norris Cancer Center, Los Angeles, California 90033, United States
Sharp Memorial Hospital, San Diego, California 92123, United States
Holy Cross Hospital, fort Lauderdale, Florida 33308, United States
Cancer Center or Florida, Ocoee, Florida 34761, United States
Integrated Community Oncology Network, Jacksonville, Florida 32256, United States
Peachtree Hematology and Oncology, Atlanta, Georgia 30309, United States
Georgia Cancer Specialists, Tucker, Georgia 30084, United States
University of Illinois, Chicago, Illinois 60612, United States
Cancer Care Specialists of Central Illinois, Decatur, Illinois 62256, United States
Cancer Institute of Alexian Brothers, Elk Grove Village, Illinois 60007, United States
Rush University Medical Center, Chicago, Illinois 60612, United States
Northern Indiana Cancer Research Consortium, South Bend, Indiana 46601, United States
Hematology-Oncology of Indiana PC, Indianapolis, Indiana 46260, United States
Indiana Oncology Hematology Consultants, Indianapolis, Indiana 46202, United States
Kansas City Cancer Center, Overland Park, Kansas 66210, United States
Louisville Oncology, Louisville, Kentucky 40202, United States
James Graham Brown Cancer Center, Louisville, Kentucky 40402, United States
Hematology-Oncology Clinic, Baton Rouge, Louisiana 70808, United States
Frederick Memorial Hospital, Frederick, Maryland 21701, United States
Tuffs-New England Medical Center, Boston, Massachusetts 20111, United States
Henry Ford Health Systems, Detroit, Michigan 48202, United States
West Michigan Regional Cancer and Blood Center, Free Soil, Michigan 49411, United States
University of Minnesota, Minneapolis, Minnesota 55455, United States
University of Missouri, Columbia, Missouri 65203, United States
Deaconess Billings Clinic, Billings, Montana 59101, United States
Nebraska Hematology-Oncology, PC, Lincoln, Nebraska 68506, United States
Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire 03756, United States
New York Oncology, Albany, New York 12208, United States
University of North Carolina, Chapel Hill, North Carolina 27599, United States
Presbyterian Hospital Cancer Center, Charlotte, North Carolina 28204, United States
The Cleveland Clinic Foundation, Cleveland, Ohio 44195, United States
Dayton Oncology and Hematology, Kettering, Ohio 45409, United States
Providence Portland Medical Center, Portland, Oregon 97213, United States
Hematology & Oncology Associates of NEPA, Dunmore, Pennsylvania 19107, United States
Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19107, United States
Mary Crowley Research Center, Dallas, Texas 75246, United States
Tyler Cancer Center, Tyler, Texas 75702, United States
Cancer Care Northwest, Spokane, Washington 99218, United States
Rainer Oncology Professional Services, Puyallup, Washington 98372, United States
University of Wisconsin, Madison, Wisconsin 53792, United States
