Clinical trial NCT00111839: Effects of Matuzumab in Combination With Pemetrexed for the Treatment of Advanced Lung Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Non Small Cell Lung Carcinoma
Keywords: Lung cancer
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
First posted: 2005-05-27
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Objective Response Assessed by Independent Review Committee
timeFrame: Baseline up to PD or death due to any cause (up to approximately 2 years)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Baseline up to PD or death due to any cause (up to approximately 3.5 years)
measure: Progression-Free Survival (PFS)
timeFrame: Baseline up to PD or death due to any cause (up to approximately 3.5 years)
measure: Duration of Objective Response Assessed by Independent Review Committee
timeFrame: From first documented objective response to PD or death due to any cause (up to approximately 3.5 years)
measure: Change From Baseline to Cycle 2 in Global Quality of Life (QoL), as Assessed Using Lung Cancer Symptom Scale (LCSS)
timeFrame: Baseline, Cycle 2 (Cycle length = 3 weeks)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Clinical Research Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas, Arkansas Cancer Research Center
state: Arkansas
city: Los Angeles
country: United States
facility: University of Southern California/Norris Cancer Center
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Jacksonville
country: United States
facility: Integrated Community Oncology Network
state: Florida
city: Ocoee
country: United States
facility: Cancer Center or Florida
state: Florida
city: Atlanta
country: United States
facility: Peachtree Hematology and Oncology
state: Georgia
city: Tucker
country: United States
facility: Georgia Cancer Specialists
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Decatur
country: United States
facility: Cancer Care Specialists of Central Illinois
state: Illinois
city: Elk Grove Village
country: United States
facility: Cancer Institute of Alexian Brothers
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Oncology Hematology Consultants
state: Indiana
city: Indianapolis
country: United States
facility: Hematology-Oncology of Indiana PC
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Overland Park
country: United States
facility: Kansas City Cancer Center
state: Kansas
city: Louisville
country: United States
facility: Louisville Oncology
state: Kentucky
city: Louisville
country: United States
facility: James Graham Brown Cancer Center
state: Kentucky
city: Baton Rouge
country: United States
facility: Hematology-Oncology Clinic
state: Louisiana
city: Frederick
country: United States
facility: Frederick Memorial Hospital
state: Maryland
city: Boston
country: United States
facility: Tuffs-New England Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health Systems
state: Michigan
city: Free Soil
country: United States
facility: West Michigan Regional Cancer and Blood Center
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Billings
country: United States
facility: Deaconess Billings Clinic
state: Montana
city: Lincoln
country: United States
facility: Nebraska Hematology-Oncology, PC
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Albany
country: United States
facility: New York Oncology
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Charlotte
country: United States
facility: Presbyterian Hospital Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Kettering
country: United States
facility: Dayton Oncology and Hematology
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Dunmore
country: United States
facility: Hematology & Oncology Associates of NEPA
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: Mary Crowley Research Center
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center
state: Texas
city: Puyallup
country: United States
facility: Rainer Oncology Professional Services
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Linz
country: Austria
facility: Research Site
city: Salzburg
country: Austria
facility: Research Site
city: Wels
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Freiburg
country: Germany
facility: Research Site
city: Gauting
country: Germany
facility: Research Site
city: Grosshansdorf
country: Germany
facility: Research Site
city: Göttingen
country: Germany
facility: Research Site
city: Halle /Saale
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Recklinghausen
country: Germany
facility: Research Site
Study officials:
affiliation: EMD Serono Inc., an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: Schiller JH, von Pawel J, Schutt P, Ansari RH, Thomas M, Saleh M, McCroskey RD, Pfeifer W, Marsland TA, Kloecker GH, Sebastian M, Pirker R, Kurek R, Beadman C, Socinski MA. Pemetrexed with or without matuzumab as second-line treatment for patients with stage IIIB/IV non-small cell lung cancer. J Thorac Oncol. 2010 Dec;5(12):1977-85. doi: 10.1097/JTO.0b013e3181f4a5c9.