Trial With Cetuximab in Maintenance Therapy After Platinum Based Chemotherapy in First Line Treatment of Non-small Cell Lung Cancer (NSCLC)
Condition: Non-Small Cell Lung Cancer (NSCLC)
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Cetuximab plus Platinum-based Doublet Chemotherapy; Cetuximab 500 mg/m^2; Cetuximab 250 mg/m^2
Intervention description: Single first dose of cetuximab 400 mg/m^2 infusion will be administered intravenously over 120 minutes (min) followed by cetuximab 250 mg/m^2 intravenous infusion over 60 min q1w with background platinum-based doublet chemotherapy up to maximum of 6 cycles, until progressive disease, unacceptable toxicity, or withdrawal of consent. Platinum based doublet chemotherapy will be administered as intravenous infusion as per study center included: vinorelbine 25 mg/m^2 on Day 1 (D1) and Day 8 (D8)+cisplatin 80 mg/m^2 on D1; or gemcitabine 1250 mg/m^2 on D1 and D8+cisplatin 75 mg/m^2 on D1; or gemcitabine 1000 mg/m^2 on D1 and D8+carboplatin at dose to reach area under curve (AUC)5 milligram*hour/milliliter (mg*hr/mL) on D1; or Docetaxel 75 mg/m^2 on D1+cisplatin 75 mg/m^2 on D1; or paclitaxel 175 mg/m^2 on D1+cisplatin 80 mg/m^2 on D1; or paclitaxel 200 mg/m^2 on D1+carboplatin at dose to reach AUC6 mg*hr/mL on D1, of each 3-week treatment cycle for a maximum of 6 cycles.; Subjects who will be free of disease progression at the end of combination therapy, will enter in the maintenance therapy period. In the maintenance period, subjects will be receive cetuximab 500 mg/m^2 as intravenous infusion every 2 weeks, until progressive disease (PD), unacceptable toxicity, or withdrawal of consent.; Subjects who will free of disease progression at the end of combination therapy, will enter in the maintenance therapy period. In the maintenance period, subjects will be receive cetuximab 250 mg/m^2 as intravenous infusion weekly, until PD, unacceptable toxicity, or withdrawal of consent.
Intervention MeSH terms: Cetuximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 583.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This open-label, randomized, multinational, non-comparative, phase IIIb trial with 2 parallel
      groups will screen about 1400 subjects with stage IIIB non-small cell lung cancer (NSCLC)
      with pleural effusion or stage IV NSCLC. It is expected that of approximately 1200 (85
      percent) subjects who will be included, about 1000 will be Caucasian; about 120 Asian, and
      the remainder (about 80) will be of other ethnic origin (that is neither Caucasian nor
      Asian). Approximately 480 (40 percent) subjects are expected to be free of progression at the
      end of combination treatment with cetuximab and platinum-based chemotherapy. These subjects
      will be eligible for randomization to intravenous cetuximab maintenance therapy with either
      500 milligram per square meter (mg/m^2) every 2 weeks or 250 mg/m^2 weekly (q1w); about 240
      subjects are expected per group.

      The trial will be performed in a community practice setting, with approximately 230 centers
      participating in the trial worldwide (planned countries are Argentina, Australia, Austria,
      Belgium, Brazil, Chile, China, Colombia, Czech Republic, France, Germany, Greece, Hong Kong,
      Hungary, India, Ireland, Israel, Italy, Mexico, Netherlands, Poland, Portugal, Russia,
      Singapore, Slovakia, South Africa, South Korea, Spain, Switzerland, Taiwan, Turkey, United
      Kingdom and Venezuela). With noncompetitive enrollment, approximately 4 to 8 subjects are
      expected to be enrolled at each center. Enrollment in the individual centers is generally
      limited to a maximum of 8 subjects. If any of these subjects does not receive trial treatment
      for any reason or discontinue all trial treatment at the first visit, additional subjects may
      be enrolled until 8 subjects were treated. The primary endpoint of the trial will be overall
      survival time from inclusion into the trial to death. Additional secondary efficacy endpoints
      will be time to treatment failure, tumor response, and disease control rate. Other endpoints
      will include safety and toxicity, compliance with maintenance therapy, subject satisfaction
      and translational research (TR) (for subjects with tumor samples available).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject has given written informed consent before any trial-related activities are
             carried out

          -  Male or female, greater than or equal to (>=)18 years of age at the time of informed
             consent, inpatient or outpatient

          -  Diagnosis of histologically or cytologically confirmed NSCLC, stage IIIB NSCLC with
             pleural effusion or stage IV

          -  Presence of at least 1 uni-dimensionally measurable index lesion, whereby index
             lesions must not lie in a previously irradiated area

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at
             inclusion in the trial

          -  White blood count>= 3 * 10^9 per liter (/L) with neutrophils >= 1.5 * 10^9 /L ,
             platelet count >=100 * 10^9 /L , and hemoglobin >= 5.6 millimole per liter (mmol/L) (9
             gram per deciliter [g/dL])

          -  Total bilirubin less than or equal to (=<)1.5 * upper limit of normal (ULN) range

          -  Aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) =< 5 * ULN

          -  Glomerular filtration rate (GFR) >=60 milliliter per minute (mL/min). The creatinine
             clearance (CrCl) estimated based on the Cockroft-Gault formula is used as a surrogate
             for the GFR

          -  Effective contraception that is, barrier method (condoms, diaphragm), oral, injectable
             or implant birth control, for both male and female subjects during the whole trial
             period and for at least 6 months after the end of trial treatment, if the risk of
             conception exists

          -  Recovered from relevant toxicities prior to inclusion in the trial

        Exclusion Criteria:

          -  Previous exposure to Epidermal Growth Factor Receptor (EGFR)-targeting therapy

          -  Previous chemotherapy for NSCLC; neo-adjuvant or adjuvant (radio-)chemotherapy is
             allowed if it was finished 6 months prior to start of trial treatment

          -  Major surgery within 30 days prior to inclusion in the trial

          -  Prior chest irradiation within 90 days prior to inclusion in the trial (palliative
             radiation of bone lesions is allowed)

          -  Participation in another clinical trial or treatment with any investigational agent(s)
             within 30 days prior to inclusion in the trial

          -  Concurrent chronic systemic immune therapy, chemotherapy for disease other than
             cancer, or hormone therapy for the treatment of cancer not indicated in the trial
             protocol

          -  Documented or symptomatic brain metastasis

          -  Pre-existing ascites Grade >= 2 and/or pericardial effusion Grade >= 2

          -  Superior vena cava syndrome contra-indicating hydration

          -  Previous malignancy in the last 5 years except basal cell carcinoma of the skin or
             pre-invasive carcinoma of the cervix

          -  Active infection (infection requiring intravenous antibiotics), including active
             tuberculosis, known and declared human immunodeficiency virus (HIV)

          -  Myocardial infarction within 6 months prior to inclusion into the trial, uncontrolled
             congestive heart failure; or any current Grade 3 or 4 cardio-vascular disorder despite
             treatment

          -  Known hypersensitivity reaction to any of the components of trial treatments

          -  Symptomatic peripheral neuropathy National Cancer Institute-Common Toxicity Criteria
             (NCI-CTC) Grade >= 2 and/or ototoxicity Grade >= 2, except if due to trauma or
             mechanical impairment due to tumor mass

          -  History of significant neurologic or psychiatric disorders including dementia,
             seizures, bipolar disorder

          -  Medical or psychological condition that would not permit the subject to complete the
             trial or sign informed consent

          -  Legal incapacity or limited legal capacity

          -  Known drug abuse

          -  Pregnancy (absence to be confirmed by serum beta-human chorionic gonadotropin
             [beta-HCG test]) or lactation period