Clinical trial NCT00820755: Trial With Cetuximab in Maintenance Therapy After Platinum Based Chemotherapy in First Line Treatment of Non-small Cell Lung Cancer (NSCLC)
Official title: Open, Randomized, Multinational Phase IIIb Trial Evaluating the Activity and Safety of Cetuximab as 250 mg/m^2 Weekly and 500 mg/m^2 Every Two Weeks Maintenance Therapy After Platinum-based Chemotherapy in Combination With Cetuximab as First-line Treatment for Subjects With Advanced Non-small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer (NSCLC)
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2009-01-12
Enrollment: 583
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, 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

Primary outcomes:
measure: Overall Survival (OS) Time
timeFrame: Time from trial inclusion to death or last day known to be alive, reported between day of first participant included, that is, Jan 2009 until cut-off date (17 Dec 2011)
measure: Percentage of Participants With 1-year Overall Survival
timeFrame: Time from trial inclusion to death or last day known to be alive, reported between day of first participant included, that is, Jan 2009 until one year after the last participant was included (March 2010)
Secondary outcomes:
measure: Overall Survival (OS) Time (From Randomization to Cetuximab Maintenance Regimen Until Death)
timeFrame: Time from randomization in cetuximab maintenance regimen to death or last day known to be alive, reported between day of first participant randomized, that is, May 2009 until cut-off date (17 Dec 2011)
measure: Time to Treatment Failure
timeFrame: Time from trial inclusion to treatment failure or last drug intake, reported between day of first participant included, that is, Jan 2009 until cut-off date (17 Dec 2011)
measure: Time to Treatment Failure (From Randomization to Cetuximab Maintenance Regimen Until Death)
timeFrame: Time from randomization in cetuximab maintenance regimen to treatment failure or last drug intake, reported between day of first participant randomized, that is, May 2009 until cut-off date (17 Dec 2011)
measure: Percentage of Participants With Best Unconfirmed Tumor Response in the Combination Therapy Phase
timeFrame: Evaluations were performed every 2 cycles during combination therapy period until progression and at the end of combination therapy period, reported between day of first participant included, that is, Jan 2009, until cut-off date, (17 Dec 2011)
measure: Percentage of Participant With Best Unconfirmed Tumor Response for the Whole Study Period
timeFrame: Evaluations were performed every 2 cycles during combination therapy and 6-weekly during maintenance therapy period until progression and at end of both periods, reported between day of first participant included, Jan 2009 until cut-off date (17 Dec 2011)
measure: Percentage of Participants With Disease Control in the Combination Therapy Phase
timeFrame: Evaluations were performed every 2 cycles during combination therapy period until progression and at the end of combination therapy period, reported between day of first participant included, that is, Jan 2009, until cut-off date, (17 Dec 2011)
measure: Percentage of Participants With Disease Control for the Whole Study Period
timeFrame: Evaluations were performed every 2 cycles during combination therapy and 6-weekly during maintenance therapy period until progression and at end of both periods, reported between day of first participant included, Jan 2009 until cut-off date (17 Dec 2011)
Other outcomes:
Locations:
city: Darmstadt
country: Germany
facility: Central Contact
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Steffen Heeger, MD MSc
role: STUDY_DIRECTOR
References:
citation: Heigener DF, Pereira JR, Felip E, Mazal J, Manzyuk L, Tan EH, Merimsky O, Sarholz B, Esser R, Gatzemeier U. Weekly and every 2 weeks cetuximab maintenance therapy after platinum-based chemotherapy plus cetuximab as first-line treatment for non-small cell lung cancer: randomized non-comparative phase IIIb NEXT trial. Target Oncol. 2015 Jun;10(2):255-65. doi: 10.1007/s11523-014-0336-7. Epub 2014 Sep 9.