Study of Taxane/Carboplatin +/- Cetuximab as First-Line Treatment for Patients With Advanced/Metastatic Non-Small Cell Lung Cancer

Non-Small-Cell Lung Carcinoma Clinical Trial

Official title:

A Randomized Multicenter Phase III Study of Taxane/Carboplatin/Cetuximab Versus Taxane/Carboplatin as First-Line Treatment for Patients With Advanced/Metastatic Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00112294
• Other study ID #: CA225-099
• Status: Completed
• Phase: Phase 3
• First received: June 1, 2005
• Last updated: November 24, 2015
• Start date: December 2004
• Est. completion date: August 2008

Study information

• Verified date: November 2015
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The primary purpose of this clinical research study is to learn if patients treated with the combination of Taxane/Carboplatin plus Cetuximab (C/T/C) have a longer progression-free survival than patients treated with Taxane/Carboplatin (T/C) alone. The safety of this treatment will also be studied.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 755
• Est. completion date: August 2008
• Est. primary completion date: April 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Must have advanced or metastatic non-small cell lung cancer that has not been previously treated with any chemotherapy.

• Tumor/disease lesions that can be measured bidimensionally.

• Must be able to carry-out work of light or sedentary nature (e.g. light house work, office work).

• Adequate recovery from recent surgery or radiation therapy.

• Must be at least 4 weeks from last major surgery or prior treatment with an investigational agent. At least 12 weeks from any radiation therapy to chest.

• Accessible for treatment, follow-up and required visits at a participating center(s).

Exclusion Criteria:

• Prior chemotherapy or adjuvant chemotherapy for the treatment of lung cancer.

• Prior treatment with cetuximab or other epidermal growth factor (EGFR)-targeted therapy.

• Prior severe infusion reaction to antibody therapy.

• Concurrent malignancy (previous malignancy without evidence of disease for 5 years will be allowed to enter trial).

• Concurrent chemotherapy or therapy with another investigational agent not indicated in the protocol.

• Serious uncontrolled medical disorders that would impair the ability to receive therapy.

• History of myocardial infarction within prior 3 months, uncontrolled angina, uncontrolled arrhythmia, or uncontrolled congestive heart failure.

• Symptomatic or uncontrolled metastases in the central nervous system. Subjects receiving a glucocorticoid for central nervous system (CNS) metastases are not eligible, but those receiving an anticonvulsant are eligible.

• Peripheral neuropathy >= grade 2 (Common Toxicity Criteria Adverse Event [CTCAE] Version 3.0).

• Inadequate hematologic and/or liver and/or kidney function.

• Sexually active and fertile individuals or partners of these individuals who are unwilling or unable to use an acceptable method of birth control for entire trial and up to 4 weeks after the study.

• Women who are pregnant or breastfeeding.

• Women with a positive pregnancy test on enrollment prior to study drug administration.

• Altered mental status or psychiatric condition that prohibits understanding or rendering of consent.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small-Cell Lung Carcinoma

Intervention

Drug:
• Paclitaxel (Taxane)
IV, 225 mg/m^2
• Docetaxel (Taxane)
IV, 75 mg/m^2
• Carboplatin
AUC=6, q 3 weeks (6 cycles maximum)
• Cetuximab
Intravenous, 400 mg/m^2, initial dose followed by 250 mg/m^2, weekly starting on Week 2

Locations

Country	Name	City	State
United States	Local Institution	Amarillo	Texas
United States	Local Institution	Anaheim	California
United States	Local Institution	Anchorage	Alaska
United States	Local Institution	Annapolis	Maryland
United States	Local Institution	Augusta	Georgia
United States	Local Institution	Bakersfield	California
United States	Local Institution	Baltimore	Maryland
United States	Local Institution	Bethlehem	Pennsylvania
United States	Local Institution	Binghamton	Connecticut
United States	Local Institution	Birmingham	Alabama
United States	Local Institution	Bismarck	North Dakota
United States	Local Institution	Bismark	North Dakota
United States	Local Institution	Boca Raton	Florida
United States	Local Institution	Boston	Massachusetts
United States	Local Institution	Boynton Beach	Florida
United States	Local Institution	Brockton	Massachusetts
United States	Local Institution	Bronx	New York
United States	Local Institution	Burlington	North Carolina
United States	Local Institution	Canton	Ohio
United States	Local Institution	Charleston	South Carolina
United States	Local Institution	Charlotte	North Carolina
United States	Local Institution	Chattanooga	Tennessee
United States	Local Institution	Cincinnati	Ohio
United States	Local Institution	Cleveland	Ohio
United States	Local Institution	Collierville	Tennessee
United States	Local Institution	Columbia	South Carolina
United States	Local Institution	Columbia	Missouri
United States	Local Institution	Columbus	Georgia
United States	Local Institution	Columbus	Ohio
United States	Local Institution	Concord	California
United States	Local Institution	Cookeville	Tennessee
United States	Local Institution	Cooperstown	New York
United States	Local Institution	Dallas	Texas
United States	Local Institution	Danville	Virginia
United States	Local Institution	Dayton	Ohio
United States	Local Institution	Dover	New Hampshire
United States	Local Institution	Dulluth	Minnesota
United States	Local Institution	Dunmore	Pennsylvania
United States	Local Institution	Evanston	Illinois
United States	Local Institution	Everett	Washington
United States	Local Institution	Flint	Michigan
United States	Local Institution	Fort Lauderdale	Florida
United States	Local Institution	Fort Myers	Florida
United States	Local Institution	Fort Wayne	Indiana
United States	Local Institution	Fountain Valley	California
United States	Local Institution	Free Soil	Michigan
United States	Local Institution	Gastonia	North Carolina
United States	Local Institution	Gilroy	California
United States	Local Institution	Grand Rapids	Michigan
United States	Local Institution	Greensboro	North Carolina
United States	Local Institution	Greenville	North Carolina
United States	Local Institution	Harrisburg	Pennsylvania
United States	Local Institution	Hartford	Connecticut
United States	Local Institution	Hazard	Kentucky
United States	Local Institution	Hickory	North Carolina
United States	Local Institution	Honolulu	Hawaii
United States	Local Institution	Houston	Texas
United States	Local Institution	Huntington	West Virginia
United States	Local Institution	Inverness	Florida
United States	Local Institution	Jackson	Michigan
United States	Local Institution	Jackson	Mississippi
United States	Local Institution	Jacksonville	Florida
United States	Local Institution	Jefferson City	Missouri
United States	Local Institution	Joliet	Illinois
United States	Local Institution	La Crosse	Wisconsin
United States	Local Institution	Lacey	Washington
United States	Local Institution	Lakeland	Florida
United States	Local Institution	Lakewood	Colorado
United States	Local Institution	Lecanto	Florida
United States	Local Institution	Long Beach	California
United States	Local Institution	Los Angeles	California
United States	Local Institution	Lubbock	Texas
United States	Local Institution	Lynchburg	Virginia
United States	Local Institution	Madison	Wisconsin
United States	Local Institution	Marietta	Georgia
United States	Local Institution	Minneapolis	Minnesota
United States	Local Institution	Mobile	Alabama
United States	Local Institution	Montebello	California
United States	Local Institution	Morganton	North Carolina
United States	Local Institution	Mt. Pleasant	South Carolina
United States	Local Institution	Muncie	Indiana
United States	Local Institution	Naperville	Illinois
United States	Local Institution	New Albany	Indiana
United States	Local Institution	New City	New York
United States	Local Institution	New London	Connecticut
United States	Local Institution	New Rochelle	New York
United States	Local Institution	Newark	New Jersey
United States	Local Institution	Normal	Illinois
United States	Local Institution	Northport	New York
United States	Local Institution	Norwich	Connecticut
United States	Local Institution	Oklahoma City	Oklahoma
United States	Local Institution	Oxnard	California
United States	Local Institution	Paducah	Kentucky
United States	Local Institution	Pembroke Pines	Florida
United States	Local Institution	Philadelphia	Pennsylvania
United States	Local Institution	Port Saint Lucie	Florida
United States	Local Institution	Pottstown	Pennsylvania
United States	Local Institution	Providence	Rhode Island
United States	Local Institution	Rancho Mirage	California
United States	Local Institution	Richmond	Virginia
United States	Local Institution	Rochester	New York
United States	Local Institution	San Diego	California
United States	Local Institution	Sayre	Pennsylvania
United States	Local Institution	Skokie	Illinois
United States	Local Institution	Spartanburg	South Carolina
United States	Local Institution	Springdale	Arkansas
United States	Local Institution	St. Louis Park	Minnesota
United States	Local Institution	Stamford	Connecticut
United States	Local Institution	Stockton	California
United States	Local Institution	Sumter	South Carolina
United States	Local Institution	Tacoma	Washington
United States	Local Institution	Tamarac	Florida
United States	Local Institution	Tampa	Florida
United States	Local Institution	Terre Haute	Indiana
United States	Local Institution	Tucson	Arizona
United States	Local Institution	Valhalla	New York
United States	Local Institution	Vincennes	Indiana
United States	Local Institution	Vista	California
United States	Local Institution	Washington	District of Columbia
United States	Local Institution	Waterbury	Connecticut
United States	Local Institution	West Reading	Pennsylvania
United States	Local Institution	Westminster	Maryland
United States	Local Institution	Wichita	Kansas
United States	Local Institution	Wilmington	North Carolina
United States	Local Institution	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	ImClone LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Median Change From Baseline in Symptoms, by Time Point	Symptoms were assessed using the FACT-LCS questionnaire. This 7-item scale has scores ranging from 0 (severely symptomatic) to 28 (symptom-free). The median change from baseline score was calculated at 3-weekly intervals. See also Outcome Measure 8.	From randomization to evidence of disease progression/death or date of last symptom assessment (up to 33 weeks).	No
Primary	Median Number of Months of Progression-free Survival (PFS)	Interval between randomization date & earliest date of disease progression/death due to any cause, assessed by the Independent Radiology Review Committee (IRRC) using modified World Health Organization (WHO) criteria to define progressive disease (PD): >=25% increase in sum of products of diameters (SOPD) of lesions compared with smallest SOPD recorded for study period or progression of any non-index lesion/appearance of new lesion. If no progression/death, date of last tumor assessment used. For participants who had no on-study tumor assessments & were still alive, date of randomization used.	From randomization to evidence of disease progression/death or date of last tumor assessment (up to 26 months).	No
Secondary	Number of Participants With Complete Response (CR) or Partial Response (PR)	Tumor response was defined as the number of participants whose best response was CR or PR, per the IRRC assessment, using the modified WHO criteria: CR: disappearance of all index/non-index lesions; PR: >= 50% reduction in the SOPD of index lesions compared with the baseline SOPD, with no evidence of progression. To qualify as CR or PR, no new lesions could be present.	From randomization to end of study drug therapy (up to 174 weeks).	No
Secondary	Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD)	Disease control was defined as the number of participants whose best response was CR, PR, or SD, per the IRRC assessment, using the modified WHO criteria: CR: disappearance of all index/non-index lesions; PR:>= 50% reduction in the SOPD of index lesions compared with the baseline SOPD, with no evidence of progression (to qualify as CR or PR, no new lesions could be present); SD: participants who did not meet the criteria for CR, PR, or PD (PD:>=25% increase in SOPD of lesions compared with smallest SOPD recorded for study period or progression of any non-index lesion/appearance of new lesion).	From randomization to end of study drug therapy (up to 174 weeks).	No
Secondary	Median Number of Months of Response	Median number of months of response (time from first occurrence of CR/PR to date of PD/death, [per IRRC assessment,using modified WHO criteria]) calculated for participants whose best response=CR/PR.For participants who did not progress/die, date of last tumor assessment used.CR:disappearance of all index/non-index lesions;PR:>= 50% reduction in SOPD of index lesions compared with baseline, no evidence of progression.No new lesions present.PD:>=25% increase in SOPD of lesions compared with smallest SOPD recorded for study period or progression of any non-index lesion/appearance of new lesion.	Time from first occurrence of CR or PR (whichever was recorded first) to the date of PD, death or date of last tumor assessment (up to 19 months).	No
Secondary	Median Number of Months to Response	The median number of months to response was calculated for participants whose best response was CR or PR. It was defined as the time from the first dose of study therapy to the first date that criteria for PR or CR (whichever occurred first)were met. Response was assessed by the IRRC, using the modified WHO criteria: CR: disappearance of all index/non-index lesions; PR: >= 50% reduction in the SOPD of index lesions compared with the baseline SOPD, with no evidence of progression. To qualify as CR or PR, no new lesions could be present.	Time from first dose of study therapy to the date of PR or CR, whichever occurred first (up to 13 months).	No
Secondary	Median Number of Months of Survival	The median number of months of survival was defined as the time from randomization to the date of death. For participants who did not die, the date of last contact was used.	From randomization to death or date of last contact (up to 41 months).	No
Secondary	Number of Participants With Improvement of Symptoms	Symptoms were assessed using the Functional Assessment of Cancer Therapy - Lung Cancer Subscale (FACT-LCS) questionnaire. This 7-item scale has scores ranging from 0 (severely symptomatic in all symptoms assessed) to 28 (symptom-free on all symptoms assessed). Symptom response (improvement) was defined as >= 2-point increase from baseline in score (maintained for 2 consecutive assessments, at least 3 weeks apart). Participants with a baseline score of >= 27 were not evaluable, as it would not have been possible to show an improvement. Participants with no baseline data were also not evaluable.	From randomization to evidence of disease progression/death or date of last symptom assessment (up to 33 weeks).	No
Secondary	Median Number of Months Until Symptomatic Progression (Worsening of Symptoms)	Symptoms were assessed using the FACT-LCS questionnaire. This 7-item scale has scores ranging from 0 (severely symptomatic) to 28 (symptom-free). Symptomatic progression was defined as >= 2-point decrease from baseline in score (maintained for 2 consecutive assessments at least 3 weeks apart). Time to symptomatic progression was defined as the time from randomization to date of symptoms worsening. For participants with no symptom progression, the date of the last symptom assessment was used. See also Outcome Measure 15.	From randomization to evidence of disease progression/death or date of last symptom assessment (up to 33 weeks).	No
Secondary	Number of Participants Who Died, or Experienced Other Serious Adverse Events (SAEs) and Adverse Events (AEs)	An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug). An SAE was defined as an AE that resulted in death, was life-threatening, required hospitalization (or prolongation of existing hospitalization), or was an important medical event.	From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).	Yes
Secondary	Number of Participants Experiencing AEs Leading to Study Drug Discontinuation	An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug). The results presented are stratified according to which drug was discontinued.	From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).	Yes
Secondary	Number of Participants Experiencing Other Significant AEs: Acneform Rash	An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug). For this study, it was decided that AEs that were categorized under the composite term "acneform rash" were of particular importance. These AEs were: rash, rash pustular, rash erythematous, dermatitis acneiform, dermatitis exfoliative, rash papular, rash pruritic, rash generalised, rash macular, rash maculo-papular, acne, acne pustular, skin desquamation and dry skin.	From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).	Yes
Secondary	Number of Participants Experiencing Other Significant AEs: Infusion Reaction	AE=any new untoward medical occurrence or worsening of pre-existing medical condition (even if not caused by the study drug). For this study, it was decided that AEs that were categorized under the composite term "infusion reaction" were of particular importance. These AEs were: infusion-related reaction, hypersensitivity, anaphylactic reaction, anaphylactic shock, and anaphylactoid reaction regardless of when they occurred. The terms dyspnea, pyrexia and chills were also grouped under infusion reaction, provided the onset date of these toxicities occurred on the first day of study treatment.	From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).	Yes
Secondary	Number of Participants Experiencing Other Significant AEs: Cardiac AEs	An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug). For this study, it was decided that AEs that were categorized under the composite term "cardiac AE" were of particular importance. These AEs, coded as preferred or other level Medical Dictionary for Regulatory Activities [MedDRA] terms were: coronary artery disorders, cardiac arrhythmias, heart failures not elsewhere classified, left ventricular failures, sudden cardiac death, cardiac death and sudden death.	From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).	Yes
Secondary	Number of Participants Who Exprienced the Most Frequent Grade 3-4 Hematology Abnormalities Occurring in >=5% Participants	Abnormalities were graded according to the National Cancer Institute (NCI) Common Toxicity Criteria (CTC), version 3.0. The scale is graded from 1 (least severe) to 4 (life threatening). Grade 3 and 4 criteria are defined as follows: Neutropenia: Grade 3, neutrophils <1.0 - 0.5 x 10^9/L; Grade 4, <0.5 x 10^9/L. Leukopenia: Grade 3, leukocytes <2.0 - 1.0 x 10^9/L; Grade 4, <1.0 x 10^9/L. Thrombocytopenia: Grade 3, platelets <50.0 - 25.0 x 10^9/L; Grade 4, <25.0 x 10^9/L. Anemia: Grade 3, hemoglobin <4.9 - 4.0 millimoles (mmol)/L, Grade 4, <4.0 mmol/L.	From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).	Yes
Secondary	Number of Participants Who Experienced the Most Frequent Grade 3-4 Serum Chemistry Abnormalities Occurring in >=5% Participants	Abnormalities were graded according to the NCI CTC, version 3.0. The scale is graded from 1 (least severe) to 4 (life threatening). Grade 3 and 4 criteria are defined as follows: Hyperglycemia (non-fasting): Grade 3, serum glucose >13.9 - 27.8 mmol/L; Grade 4 >27.8 mmol/L or acidosis. Hypomagnesemia: Grade 3, serum magnesium >1.23 - 3.30 mmol/L; Grade 4 >3.30 mmol/L. Hyponatremia: Grade 3, serum sodium <130 - 120 mmol/L; Grade 4 <120 mmol/L. Low albumin: Grade 3, serum albumin <20 g/L; Grade 4 not applicable.	From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).	Yes
Secondary	Number of Participants Who Had Unscheduled Visits to Physicians, Clinics, Hospitals and Other Unscheduled Major Medicinal Procedures	Participants were to complete log to collect information on unscheduled visits to physicians,clinics,hospitals & other unscheduled major procedures.If asked, participants were to complete and return log to site upon routinely scheduled visits.The purpose of this exploratory analysis was to understand the economical implications as a secondary objective.This was not a pivotal study & therefore not needed to support any arguments with regulatory authorities concerning cost-benefit,hence,it was not necessary to conduct this analysis. There is no intent on conducting this analysis in the future.	Day 1 of each cycle of treatment, at the end of study therapy evaluation and at the first follow-up visit (6 weeks after the end of study therapy evaluation).	No

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm