Status:
COMPLETED
Cilengitide and Cetuximab in Combination With Platinum-based Chemotherapy as First-line Treatment for Subjects With Advanced Non Small Cell Lung Cancer (NSCLC)
Lead Sponsor:
Merck KGaA, Darmstadt, Germany
Conditions:
Carcinoma, Non-Small-Cell Lung
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
Primary objective of the study's Safety run-in: \- To determine the maximum tolerated dose (MTD) of cilengitide in combination with cetuximab, and platinum-based chemotherapy (cisplatin/vinorelbine o...
Detailed Description
Schedule of visits and assessments: Pre-screening Visit (Within 2 weeks prior to screening): In an initial step subjects with newly diagnosed NSCLC (suspected or already established diagnosis) will ...
Eligibility Criteria
Inclusion
- Inclusion criteria:
- Written informed consent obtained before undergoing any study-related activities.
- Male or female, at least 18 years of age
- Histologically confirmed NSCLC, Stage IIIb with documented malignant pleural effusion or Stage IV (according to staging system 6th edition)
- EGFR expression greater than or equal to (\>=) 200 on tumor tissue determined by local testing using the kit and testing procedures described in the study Manual of Operations (MOP)
- Archived tumor material sample for central histology and further biomarker research including mutational analysis of genes such as EGFR, k-ras, b-raf (material details described in the study MOP)
- At least 1 radiographically documented measurable lesion in a previously non-irradiated area according to evaluation criteria in solid tumors (RECIST), i.e. this lesion must be adequately measurable in at least 1 dimension (longest diameter \[LD\] to be recorded) as \>=2 centimeter (cm) by conventional techniques or ≥1 cm by spiral CT scan
- Eastern Cooperative Oncology Group (ECOG)-performance status 0-1
- Leukocyte count \>=3.0 x 10\^9 per liter (/L)
- Absolute neutrophil count (ANC) \>=1.5 x 10\^9/L
- Platelets \>=100 x 10\^9/L
- Hemoglobin \>=9 gram per deciliter (g/dL) (without transfusions)
- Bilirubin less than or equal to (\<=) 1.5 x upper limit of normality (ULN)
- Aspartate Aminotransferase (AST) \<=5 x ULN and Alanine Aminotransferase (ALT) \<=5 x ULN
- Serum creatinine \<=1.25 x ULN and/or creatinine clearance \>=60 milliliter per minute (mL/min)
- Prothrombin time (PT), international normalized ratio (INR) within normal limits and partial thromboplastin time (PTT) below upper limit of normal.
- Sodium and potassium within normal limits or \<=10% above or below (supplementation permitted).
- Effective contraception for both male and female subjects (if the risk of conception exists). If female, she must: be neither pregnant nor breast-feeding, nor attempting to conceive, use a highly effective method of contraception for at least 7 days before entry into the trial, throughout the entire duration of the trial and for 6 months following completion of the last dose of trial medication. A highly effective method of contraception is defined as those which result in a low failure rate (that is, \<1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, intrauterine devices (IUDs) (hormonal or copper-based), sexual abstinence or vasectomized partner, or be post-menopausal or surgically sterilized. If male, he must be willing to use contraception to avoid pregnancies for at least 7 days before entry into the trial, throughout the entire duration of the trial and for 6 months following the last dose of trial medication. Two negative semen analyses post-vasectomy have to be available in order to be considered infertile
- Exclusion criteria:
- Prior treatment with an antibody or molecule targeting EGFR- and/or vascular endothelial growth factor receptor (VEGFR)-related signaling pathways
- Previous chemotherapy for NSCLC including prior adjuvant therapy
- History of or current brain metastasis and/or leptomeningeal disease (known or suspected)
- Radiotherapy (except localized radiotherapy for pain relief), major surgery or any intake of investigational drug in the 30 days before the start of study treatment entry
- Concurrent chronic immunosuppressive or hormone anti-cancer therapy (physiologic hormone replacement or corticosteroid treatment for chronic obstructive pulmonary disease \[COPD\] is allowed)
- Clinically relevant coronary artery disease (New York Heart Association \[NYHA\] functional angina classification III/IV), congestive heart failure (NYHA III/IV), clinically relevant cardiomyopathy, history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia
- History of coagulation disorder associated with bleeding, recurrent or recent thrombotic events or history of hemoptysis related to bronchopulmonary cancer. Hemoptysis is defined as coughing more than a teaspoon of red blood per day
- Recent peptic ulcer disease (endoscopically proven gastric, duodenal or esophageal ulcer) within 6 months of study treatment start
- Presence of any contra-indication to treatment with cilengitide, cetuximab, cisplatin and vinorelbine or gemcitabine including:
- Known hypersensitivity to cilengitide, cetuximab, cisplatin, vinorelbine, or gemcitabine or to any of the excipients of these drugs
- Superior vena cava syndrome contra-indicating hydration
- Symptomatic peripheral neuropathy National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade \>=2 and/or ototoxicity NCI CTC AE Grade \>=2, except if due to trauma or mechanical impairment due to tumor mass
- Phenytoin (introduced to prevent the anticonvulsant effect of certain anticancer drugs) (contra-indication for cisplatin)
- Yellow Fever Vaccine, Live Attenuated Vaccines (contra-indications for cisplatin)
- Pregnancy or lactation period
- Concurrent treatment with a non-permitted drug
- Treatment with any other investigational product within the past 30 days
- Previous malignancy other than NSCLC in the last 5 years except for basal cell cancer of the skin or pre-invasive cancer of the cervix
- Medical or psychological conditions that would not permit the subject to complete the study or sign informed consent
- Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such
- Patients with hepatitis, massive liver metastases (\>75%), current alcoholism or liver cirrhosis (because of vinorelbine and gemcitabine)
- Patients who have been therapeutically anticoagulated
- Legal incapacity or limited legal capacity
- Significant disease (for example, interstitial lung disease) which, in the investigator's opinion, would exclude the subject from the study
Exclusion
Key Trial Info
Start Date :
February 1 2009
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
July 1 2013
Estimated Enrollment :
232 Patients enrolled
Trial Details
Trial ID
NCT00842712
Start Date
February 1 2009
End Date
July 1 2013
Last Update
January 13 2017
Active Locations (44)
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1
Research Site
Antwerpen (Edegem), Belgium
2
Research Site
Brasschaat, Belgium
3
Research Site
Brussels, Belgium
4
Research Site
Gosselies, Belgium