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

NCT ID: NCT00820755

Last Updated: 2014-05-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 583 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2013-06-30

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).

Conditions

Non-Small Cell Lung Cancer (NSCLC)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cetuximab 250 mg/m^2 q1w + Platinum-based Doublet Chemotherapy

Group Type: ACTIVE_COMPARATOR

Cetuximab plus Platinum-based Doublet Chemotherapy

Intervention Type: DRUG

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.

Cetuximab 500 mg/m^2 every 2 weeks

Group Type: ACTIVE_COMPARATOR

Cetuximab 500 mg/m^2

Intervention Type: DRUG

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.

Cetuximab 250 mg/m^2 weekly

Group Type: ACTIVE_COMPARATOR

Cetuximab 250 mg/m^2

Intervention Type: DRUG

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.

Interventions

Cetuximab plus Platinum-based Doublet Chemotherapy

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.

Intervention Type: DRUG

Cetuximab 500 mg/m^2

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.

Intervention Type: DRUG

Cetuximab 250 mg/m^2

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 Type: DRUG

Other Intervention Names

Erbitux; Erbitux

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steffen Heeger, MD MSc

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

Central Contact

Darmstadt, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 25195590 (View on PubMed)

Other Identifiers

EMR 62240-506

Identifier Type: -

Identifier Source: org_study_id