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

Primary Purpose

Non-Small-Cell Lung Carcinoma

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Paclitaxel (Taxane)

Docetaxel (Taxane)

Carboplatin

Cetuximab

About this trial

This is an interventional treatment trial for Non-Small-Cell Lung Carcinoma focused on measuring Non-Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Cetuximab+Taxane+Carboplatin (C/T/C)

Taxane+Carboplatin (T/C)

Arm Description

Cetuximab was administered at an initial dose (Week 1) of 400 mg/m^2 intravenous (IV) infusion (infused over 120 minutes) and a weekly maintenance dose of 250 mg/m^2 IV infusion (infused over 60 minutes). A cycle of therapy was defined as 3 weeks. Taxane was paclitaxel 225 mg/m^2 infused over 180 minutes on Day 1 and subsequently every 3 weeks or docetaxel 75 mg/m^2 infused over 60 minutes on Day 1 and subsequently every 3 weeks. Carboplatin was infused over 30 minutes on Day 1 and subsequently every 3 weeks.

A cycle of therapy was defined as 3 weeks. Taxane was paclitaxel 225 mg/m^2 infused over 180 minutes on Day 1 and subsequently every 3 weeks or docetaxel 75 mg/m^2 infused over 60 minutes on Day 1 and subsequently every 3 weeks. Carboplatin was infused over 30 minutes on Day 1 and subsequently every 3 weeks.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT00112294

First Posted

June 1, 2005

Last Updated

November 24, 2015

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT00112294

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2015

Overall Recruitment Status

Completed

Study Start Date

December 2004 (undefined)

Primary Completion Date

April 2007 (Actual)

Study Completion Date

August 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-Small-Cell Lung Carcinoma

Keywords

Non-Small Cell Lung Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

755 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cetuximab+Taxane+Carboplatin (C/T/C)

Arm Type

Active Comparator

Arm Description

Arm Title

Taxane+Carboplatin (T/C)

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Paclitaxel (Taxane)

Intervention Description

IV, 225 mg/m^2

Intervention Type

Drug

Intervention Name(s)

Docetaxel (Taxane)

Intervention Description

IV, 75 mg/m^2

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Intervention Description

AUC=6, q 3 weeks (6 cycles maximum)

Intervention Type

Drug

Intervention Name(s)

Cetuximab

Other Intervention Name(s)

Erbitux

Intervention Description

Intravenous, 400 mg/m^2, initial dose followed by 250 mg/m^2, weekly starting on Week 2

Primary Outcome Measure Information:

Title

Median Number of Months of Progression-free Survival (PFS)

Description

Time Frame

From randomization to evidence of disease progression/death or date of last tumor assessment (up to 26 months).

Secondary Outcome Measure Information:

Title

Number of Participants With Complete Response (CR) or Partial Response (PR)

Description

Time Frame

From randomization to end of study drug therapy (up to 174 weeks).

Title

Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD)

Description

Time Frame

From randomization to end of study drug therapy (up to 174 weeks).

Title

Median Number of Months of Response

Description

Time Frame

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).

Title

Median Number of Months to Response

Description

Time Frame

Time from first dose of study therapy to the date of PR or CR, whichever occurred first (up to 13 months).

Title

Median Number of Months of Survival

Description

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.

Time Frame

From randomization to death or date of last contact (up to 41 months).

Title

Number of Participants With Improvement of Symptoms

Description

Time Frame

From randomization to evidence of disease progression/death or date of last symptom assessment (up to 33 weeks).

Title

Median Number of Months Until Symptomatic Progression (Worsening of Symptoms)

Description

Time Frame

From randomization to evidence of disease progression/death or date of last symptom assessment (up to 33 weeks).

Title

Number of Participants Who Died, or Experienced Other Serious Adverse Events (SAEs) and Adverse Events (AEs)

Description

Time Frame