Trial With Cetuximab in Maintenance Therapy After Platinum Based Chemotherapy in First Line Treatment of Non-small Cell Lung Cancer (NSCLC) (NEXT)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT00820755
First received: January 9, 2009
Last updated: October 4, 2012
Last verified: October 2012

January 9, 2009
October 4, 2012
January 2009
December 2011   (final data collection date for primary outcome measure)
Overall Survival (OS) Time [ Time Frame: Time from trial inclusion to death, reported between day of first patient included, Jan 2009, until cut off date. ] [ Designated as safety issue: No ]
Time from trial inclusion to death. Patients without event are censored at the last date known to be alive or at the clinical cut-off date, whichever is earlier.
The primary endpoint in this trial is overall survival time (OS) defined as the time (in months) from trial inclusion to death. [ Time Frame: Overall Survival Time ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00820755 on ClinicalTrials.gov Archive Site
  • OS Time (From randomisation to cetuximab maintenance regimen until death) [ Time Frame: Time from randomisation to cetuximab maintenance regimen to death, reported between day of first patient randomized, May 2009, until cut off date. ] [ Designated as safety issue: No ]
    Time from randomisation to cetuximab maintenance regimen to death. Patients without event are censored at the last date known to be alive or at the clinical cut-off date, whichever is earlier.
  • Time to Treatment Failure [ Time Frame: Time from trial inclusion to treatment failure or last tumour assessment, reported between day of first patient included, Jan 2009, until cut off date. ] [ Designated as safety issue: No ]
    Time from trial inclusion to date of either first occurrence of progression, discontinuation of treatment due to progression or adverse event, withdrawal of consent or lost to follow up, start of further anticancer therapy, or death. Patients without events will be censored either at the time of their last drug intake, or on the day of inclusion (day 1) if they received no study drug.
  • Time to Treatment Failure (from randomisation to cetuximab maintenance regimen until death) [ Time Frame: Time from randomisation to cetuximab maintenance regimen to treatment failure or last tumour assessment, reported between day of first patient randomized, May 2009, until cut off date. ] [ Designated as safety issue: No ]
    Time from randomisation to cetuximab maintenance regimen to date of either first occurrence of progression, discontinuation of treatment due to progression or adverse event, withdrawal of consent or lost to follow up, start of further anticancer therapy, or death. Patients without events will be censored either at the time of their last drug intake, or on the day of randomization (day 1 of maintenance therapy) if they received no study drug.
  • Unconfirmed Tumor Response [ Time Frame: Evaluations were performed every 2 cycles within combination therapy period and 6-weekly evaluation visits during the maintenance therapy until progression, reported between day of first patient included, Jan 2009, until cut-off date. ] [ Designated as safety issue: No ]
    The response rate is defined as the percentage of subjects having achieved complete response and partial response as the unconfirmed best overall response according to radiological assessments based on RECIST criteria.
  • Disease control [ Time Frame: Evaluations were performed every 2 cycles within combination therapy period and 6-weekly evaluation visits during the maintenance therapy until progression, reported between day of first patient included, Jan 2009, until cut-off date. ] [ Designated as safety issue: No ]
    The disease control rate is defined as the percentage of subjects having achieved complete response or partial response or stable disease as the unconfirmed best overall response according to radiological assessments based on RECIST criteria.
  • Overall survival time from randomization to cetuximab maintenance therapy [ Time Frame: Overall Survival Time ] [ Designated as safety issue: No ]
  • Time to treatment failure [ Time Frame: Overall Survival Time ] [ Designated as safety issue: No ]
  • Time to treatment failure from randomization to cetuximab maintenance therapy [ Time Frame: Overall Survival Time ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Trial With Cetuximab in Maintenance Therapy After Platinum Based Chemotherapy in First Line Treatment of Non-small Cell Lung Cancer (NSCLC)
Open, Randomized, Multinational Phase IIIb Trial Evaluating the Activity and Safety of Cetuximab as 250 mg/m2 Weekly and 500 mg/m2 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).

This open-label, randomized, multinational, non-comparative, phase IIIb trial with 2 parallel groups will screen about 1400 subjects with stage IIIB NSCLC with pleural effusion or stage IV NSCLC. It is expected that of approximately 1200 (85%) subjects who will be included, about 1000 will be Caucasian; about 120 Asian, and the remainder (about 80) will be of other ethnic origin (i.e. neither Caucasian nor Asian). Approximately 480 (40%) 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 mg/m² every 2 weeks (group A) or 250 mg/m² every week (group B); 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 enrolment, approximately 4 to 8 subjects are expected to be enrolled at each center. Enrolment 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 TR (for subjects with tumor samples available)

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Non-Small Cell Lung Cancer (NSCLC)
  • Drug: Cetuximab

    Combination therapy phase: Subjects will receive 4-6 cycles of selected platinum-based chemotherapy in combination with weekly administration of Cetuximab 5 mg/mL for intravenous infusion First dose: Cetuximab 400 mg/m², infusion time: 120 min. Subsequent doses: Cetuximab 250 mg/m², infusion time 60 min.

    Maintenance therapy phase: Subjects who are not progressing at the end of the combination therapy phase will be randomised. Patients assigned to this arm will receive Cetuximab 500 mg/m² every 2 weeks.

  • Drug: Cetuximab

    Combination therapy phase: Subjects will receive 4-6 cycles of selected platinum-based chemotherapy in combination with weekly administration of Cetuximab 5 mg/mL for intravenous infusion First dose: Cetuximab 400 mg/m², infusion time: 120 min. Subsequent doses: Cetuximab 250 mg/m², infusion time 60 min.

    Maintenance therapy phase: Subjects who are not progressing at the end of the combination therapy phase will be randomised. Patients assigned to this arm will receive Cetuximab 250 mg/m² once weekly.

  • Active Comparator: 1
    Intervention: Drug: Cetuximab
  • Active Comparator: 2
    Intervention: Drug: Cetuximab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
583
December 2012
December 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

For inclusion in the trial, all of the following inclusion criteria must be fulfilled:

  • Subject has given written informed consents before any trial-related activities are carried out
  • Male or female, ≥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
  • ECOG performance status of 0 or 1 at inclusion in the trial
  • White blood count ≥3 x 10^9/L with neutrophils ≥1.5 x 10^9/L, platelet count ≥100 x 10^9/L, and hemoglobin ≥5.6 mmol/L (9 g/dL)
  • Total bilirubin ≤1.5 x upper limit of normal (ULN) range
  • Aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤5 x ULN
  • Glomerular filtration rate (GFR) ≥60 mL/min. The creatinine clearance estimated by the Cockroft-Gault formula will be used as a surrogate for the GFR
  • Effective contraception i.e., 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:

Subjects are not eligible for this trial if they fulfill any of the following exclusion criteria:

  • Previous exposure to 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 [IV] 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 β-HCG test) or lactation period
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT00820755
EMR 62240-506
Not Provided
Merck KGaA
Merck KGaA
Not Provided
Study Director: Steffen Heeger, MD MSc Merck KGaA
Merck KGaA
October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP