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

NCT00820755 | Completed Phase 3 Results

• 1 other identifier: EMR 62240-506
• Study Type: interventional
• Target: 583
• Locations: 1 country
• Sites: 1

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)

Outcome Measures

Primary Outcomes (2)

• Overall Survival (OS) Time

  The OS time is defined as the time from trial inclusion to death. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whichever is earlier.

  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)

• Percentage of Participants With 1-year Overall Survival

  The OS time is defined as the time from trial inclusion to death. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whichever is earlier. Percentage of participants who were still alive until one year after the last participant was included (March 2010).

  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 (7)

• Overall Survival (OS) Time (From Randomization to Cetuximab Maintenance Regimen Until Death)

  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)

• Time to Treatment Failure

  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)

• Time to Treatment Failure (From Randomization to Cetuximab Maintenance Regimen Until Death)

  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)

• Percentage of Participants With Best Unconfirmed Tumor Response in the Combination Therapy Phase

  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)

• Percentage of Participant With Best Unconfirmed Tumor Response for the Whole Study Period

  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)

Study Arms (3)

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

ACTIVE COMPARATOR

Drug: Cetuximab plus Platinum-based Doublet Chemotherapy

Cetuximab 500 mg/m^2 every 2 weeks

ACTIVE COMPARATOR

Drug: Cetuximab 500 mg/m^2

Cetuximab 250 mg/m^2 weekly

ACTIVE COMPARATOR

Drug: Cetuximab 250 mg/m^2

Interventions

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

Cetuximab 500 mg/m^2 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.

Also known as: Erbitux

Cetuximab 500 mg/m^2 every 2 weeks

Cetuximab 250 mg/m^2 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.

Also known as: Erbitux

Cetuximab 250 mg/m^2 weekly

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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)
• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

Central Contact

Darmstadt, Germany

Location

Related Publications (1)

• 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.

  PMID: 25195590 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Enrollment was stopped prematurely when cetuximab did not gain regulatory approval in this indication.

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Serono, a division of Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Steffen Heeger, MD MSc

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2009
• First Posted: January 12, 2009
• Study Start: January 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: June 1, 2013
• Last Updated: May 5, 2014
• Results First Posted: May 5, 2014

Record last verified: 2014-04

Locations

DE (1)