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

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00111839
• Other study ID #: EMD 72000-031
• Secondary ID: 2006-000899-32
• Status: Completed
• Phase: Phase 2
• First received: May 26, 2005
• Last updated: April 5, 2018
• Start date: May 31, 2005
• Est. completion date: March 31, 2009

Study information

• Verified date: April 2018
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: March 31, 2009
• Est. primary completion date: July 31, 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 [ß-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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms
• Non Small Cell Lung Carcinoma

Intervention

Drug:
• Pemetrexed
Pemetrexed will be administered IV until PD or the occurrence of unacceptable toxicity.
• Matuzumab
Matuzumab will be administered IV until PD or the occurrence of unacceptable toxicity.

Locations

Country	Name	City	State
Austria	Research Site	Linz
Austria	Research Site	Salzburg
Austria	Research Site	Wels
Austria	Research Site	Wien
Germany	Research Site	Essen
Germany	Research Site	Freiburg
Germany	Research Site	Gauting
Germany	Research Site	Göttingen
Germany	Research Site	Grosshansdorf
Germany	Research Site	Halle /Saale
Germany	Research Site	Hamburg
Germany	Research Site	Heidelberg
Germany	Research Site	Köln
Germany	Research Site	Mainz
Germany	Research Site	München
Germany	Research Site	Recklinghausen
United States	New York Oncology	Albany	New York
United States	Peachtree Hematology and Oncology	Atlanta	Georgia
United States	Hematology-Oncology Clinic	Baton Rouge	Louisiana
United States	Deaconess Billings Clinic	Billings	Montana
United States	Tuffs-New England Medical Center	Boston	Massachusetts
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Presbyterian Hospital Cancer Center	Charlotte	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	University of Missouri	Columbia	Missouri
United States	Mary Crowley Research Center	Dallas	Texas
United States	Cancer Care Specialists of Central Illinois	Decatur	Illinois
United States	Henry Ford Health Systems	Detroit	Michigan
United States	Hematology & Oncology Associates of NEPA	Dunmore	Pennsylvania
United States	Cancer Institute of Alexian Brothers	Elk Grove Village	Illinois
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Frederick Memorial Hospital	Frederick	Maryland
United States	West Michigan Regional Cancer and Blood Center	Free Soil	Michigan
United States	Hematology-Oncology of Indiana PC	Indianapolis	Indiana
United States	Indiana Oncology Hematology Consultants	Indianapolis	Indiana
United States	Integrated Community Oncology Network	Jacksonville	Florida
United States	Dayton Oncology and Hematology	Kettering	Ohio
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Nebraska Hematology-Oncology, PC	Lincoln	Nebraska
United States	University of Arkansas, Arkansas Cancer Research Center	Little Rock	Arkansas
United States	University of Southern California/Norris Cancer Center	Los Angeles	California
United States	James Graham Brown Cancer Center	Louisville	Kentucky
United States	Louisville Oncology	Louisville	Kentucky
United States	University of Wisconsin	Madison	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Cancer Center or Florida	Ocoee	Florida
United States	Kansas City Cancer Center	Overland Park	Kansas
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Rainer Oncology Professional Services	Puyallup	Washington
United States	Sharp Memorial Hospital	San Diego	California
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	Cancer Care Northwest	Spokane	Washington
United States	Georgia Cancer Specialists	Tucker	Georgia
United States	Arizona Clinical Research Center	Tucson	Arizona
United States	Tyler Cancer Center	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
EMD Serono

Countries where clinical trial is conducted

United States,  Austria,  Germany, 

References & Publications (1)

Schiller JH, von Pawel J, Schütt 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 st — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Objective Response Assessed by Independent Review Committee	Objective response was defined as having a complete response (CR) or a partial response (PR). Response assessment was performed using modified World Health Organization (WHO) criteria. Complete response: disappearance of all index and non-index lesions, without appearance of any new lesion. PR: greater than (>) 50 percent (%) decrease from baseline in sum of product of diameters of index lesions, without appearance of any new lesion.	Baseline up to PD or death due to any cause (up to approximately 2 years)
Secondary	Overall Survival (OS)	OS was defined as the duration from randomization to death (due to any cause). OS was estimated using Kaplan-Meier analysis.	Baseline up to PD or death due to any cause (up to approximately 3.5 years)
Secondary	Progression-Free Survival (PFS)	PFS was defined as the time from randomization to the first documentation of disease progression (PD) or to death due to any cause, whichever occurred first. PD: >25% increase in one or more lesions, or appearance new lesions. PFS was estimated using Kaplan-Meier analysis.	Baseline up to PD or death due to any cause (up to approximately 3.5 years)
Secondary	Duration of Objective Response Assessed by Independent Review Committee	Objective response was defined as having a CR or a PR. Response assessment was performed using modified WHO criteria. CR: disappearance of all index and non-index lesions, without appearance of any new lesion. PR: >50% decrease from baseline in sum of product of diameters of index lesions, without appearance of any new lesion. Duration of objective response was defined as time from first appearance of CR or PR to time of PD (>25% increase in one or more lesions, or appearance new lesions) or death. Duration of objective response was to be assessed using Kaplan-Meier analysis.	From first documented objective response to PD or death due to any cause (up to approximately 3.5 years)
Secondary	Change From Baseline to Cycle 2 in Global Quality of Life (QoL), as Assessed Using Lung Cancer Symptom Scale (LCSS)	The LCSS consisted of 9 items: 6 items focused on lung cancer symptoms (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain] and 3 items were global items (symptom distress, interference with activity level, and global QoL). The global QoL item scores are reported here. The total global QoL item score ranged from 0 (worse QoL) to 100 (best QoL).	Baseline, Cycle 2 (Cycle length = 3 weeks)

External Links

•   EudraCT results summary synopsis