Phase 3
N=583
Trial With Cetuximab in Maintenance Therapy After Platinum Based Chemotherapy in First Line Treatment of Non-small Cell Lung Cancer (NSCLC)
Non-Small Cell Lung Cancer (NSCLC)
Bottom Line
View on ClinicalTrials.gov: NCT00820755 ↗Enrolled (actual)
583
Serious AEs
34.2%
Results posted
May 2014
Primary outcome: Primary: Overall Survival (OS) Time — 16.1; 15.5 months
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Cetuximab plus Platinum-based Doublet Chemotherapy (Drug); Cetuximab 500 mg/m^2 (Drug); Cetuximab 250 mg/m^2 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck KGaA, Darmstadt, Germany
- Primary completion
- Dec 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Survival (OS) Time |
16.1; 15.5 | — |
| PRIMARY Percentage of Participants With 1-year Overall Survival |
62.8; 64.4 | — |
| SECONDARY Overall Survival (OS) Time (From Randomization to Cetuximab Maintenance Regimen Until Death) |
12.6; 12.6 | 0.1265 |
| SECONDARY Time to Treatment Failure |
5.8; 6.6 | — |
| SECONDARY Time to Treatment Failure (From Randomization to Cetuximab Maintenance Regimen Until Death) |
2.6; 2.8 | 0.0622 |
| SECONDARY Percentage of Participants With Best Unconfirmed Tumor Response in the Combination Therapy Phase |
36.2 | — |
| SECONDARY Percentage of Participant With Best Unconfirmed Tumor Response for the Whole Study Period |
54.8; 57.8 | — |
| SECONDARY Percentage of Participants With Disease Control in the Combination Therapy Phase |
65.7 | — |
| SECONDARY Percentage of Participants With Disease Control for the Whole Study Period |
98.7; 99.4 | — |
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 (= =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
Data sourced from ClinicalTrials.gov (NCT00820755). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.