Lung Cancer
Conditions
Keywords
bronchioalveolar carcinoma (BAC), adenocarcinoma with BAC features, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, recurrent non-small cell lung cancer, cetuximab
Brief summary
RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. PURPOSE: This phase II trial is studying how well cetuximab works in treating patients with recurrent or stage IIIB or stage IV lung cancer.
Detailed description
OBJECTIVES: Primary * Determine the objective response rate in patients with recurrent or stage IIIB or IV bronchoalveolar carcinoma (BAC) or adenocarcinoma of the lung with BAC features treated with cetuximab. Secondary * Determine the overall survival and time to progression in patients treated with this drug. * Determine the toxic effects of this drug in these patients. * Correlate expression of total and phosphorylated epidermal growth factor receptor (EGFR), total and phosphorylated AKT3, and total and phosphorylated MAPKinase with response in patients treated with this drug. * Determine whether the presence of polymorphisms or mutations in the EGFR gene influences response in patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive cetuximab IV over 1-2 hours once on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years. ACTUAL ACCRUAL: A total of 72 patients were accrued for this study.
Interventions
BIOLOGICALcetuximab
Sponsors
National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed bronchoalveolar carcinoma (BAC) or adenocarcinoma of the lung with BAC features meeting 1 of the following stage criteria: * Stage IIIB disease (with pleural or pericardial effusion) * Stage IV disease * Recurrent disease * Measurable disease * Tumor tissue available from biopsy * Age of 18 and over * ECOG performance status of 0-2 * Life expectancy greater than 3 months * White blood cell (WBC) ≥ 3,000/mm\^3 * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Bilirubin normal * Aspartate aminotransferase (AST) and/or alanine aminotranferease (ALT) ≤ 2.5 times upper limit of normal * Creatinine normal OR Creatinine clearance ≥ 60 mL/min * No more than 1 prior chemotherapy regimen for advanced BAC * More than 3 years since prior chemotherapy for other malignancies * At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) for this malignancy and recovered * HIV-positive patients are eligible provided the following criteria are met: * CD4 count ≥ 100/mm\^3 * Undetectable viral load within the past 3 months * Receiving a stable antiretroviral regimen for ≥ 4 weeks before study entry * Fertile patients must use effective contraception * At least 2 weeks since prior radiotherapy and recovered
Exclusion criteria
* Untreated brain metastases * Patients with stable brain metastases ≥ 4 weeks after external beam radiotherapy to the brain are eligible * Acute hepatitis * Symptomatic congestive heart failure * Uncontrolled hypertension * Unstable angina pectoris * Cardiac arrhythmia * Pregnant or nursing * Prior allergic reaction to chimerized or murine monoclonal antibody therapy * Documented presence of human anti-mouse antibodies * Ongoing or active infection * Psychiatric illness or social situation that would preclude study compliance * Other uncontrolled illness * Prior cetuximab * Concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) * Other prior known epidermal growth factor receptor inhibitors (e.g., gefitinib or erlotinib) * Other concurrent investigational agents * Other concurrent anticancer therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (Proportion of Patients With Objective Response) | Assessed every 8 weeks during treatment; after off-treatment, every 3 months for 2 years and then every 6 months for 3 years | Response was evaluated using RECIST 1.0 criteria. Per RECIST criteria, Complete response (CR)= disappearance of all target and nontarget lesions Partial response (PR)= \>=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Objective response = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival by Smoking Status | Overall survival assessed every week during treatment; after off-treatment, every 3 months for 2 years and then every 6 months for 3 years. Smoking status evaluated at baseline | Medians of overall survival by smoking status are reported. |
| Time to Progression | Assessed every 8 weeks during treatment; after off-treatment, every 3 months for 2 years and then every 6 months for 3 years | Time to progression is defined as time from study entry until disease progression. Progression is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s) or unequivocal progression of existing nontarget lesions. |
| Overall Survival | Every week during treatment; after off-treatment, every 3 months for 2 years and then every 6 months for 3 years | Overall survival is defined as the time from registration to death. |
| Time to Progression by Smoking Status | Progression assessed every 8 weeks during treatment; after off-treatment, every 3 months for 2 years and then every 6 months for 3 years. Smoking status evaluated at baseline | Medians of time to progression by smoking status are reported. |
Countries
United States
Participant flow
Recruitment details
The study opened to accrual on August 10, 2005, accrued its first patient on October 13, 2005, and closed to accrual on December 12, 2008 with final accrual of 72 patients.
Participants by arm
| Arm | Count |
|---|---|
| Cetuximab Cetuximab was given as a weekly intravenous (IV) infusion (over 60 minutes) at 250 mg/m2 from week 2 onwards after an initial loading dose of 400 mg/m2 (over 120 minutes) on week 1 until disease progression or unacceptable toxicity. The infusion rate of cetuximab could not exceed 5 mL/min. Each cycle will be 28 days in length. To prevent a hypersensitivity reaction, all patients were premedicated with diphenhydramine hydrochloride 50 mg (or an equivalent antihistamine) by IV (over 30-60 minutes) prior to the first dose of cetuximab. Premedication might be administered prior to subsequent doses, but at the investigator's discretion, the dose of diphenhydramine (or a similar agent) was reduced.
Only eligible patients with confirmed diagnosis are included in the main analysis. | 41 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Death | 1 |
| Overall Study | Diagnosis of BAC not confirmed | 27 |
| Overall Study | Ineligible | 4 |
| Overall Study | Other complicating disease | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Cetuximab |
|---|---|
| Age, Continuous | 70 years |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 70 / 72 |
| serious Total, serious adverse events | 27 / 72 |
Outcome results
Primary
Objective Response Rate (Proportion of Patients With Objective Response)
Response was evaluated using RECIST 1.0 criteria. Per RECIST criteria, Complete response (CR)= disappearance of all target and nontarget lesions Partial response (PR)= \>=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Objective response = CR + PR.
Time frame: Assessed every 8 weeks during treatment; after off-treatment, every 3 months for 2 years and then every 6 months for 3 years
Population: Only eligible and treated patients with confirmed diagnosis are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab | Objective Response Rate (Proportion of Patients With Objective Response) | 0.07 Proportion |
Secondary
Overall Survival
Overall survival is defined as the time from registration to death.
Time frame: Every week during treatment; after off-treatment, every 3 months for 2 years and then every 6 months for 3 years
Population: Only eligible and treated patients with confirmed diagnosis are included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab | Overall Survival | 17.9 Months |
Secondary
Overall Survival by Smoking Status
Medians of overall survival by smoking status are reported.
Time frame: Overall survival assessed every week during treatment; after off-treatment, every 3 months for 2 years and then every 6 months for 3 years. Smoking status evaluated at baseline
Population: Only eligible and treated patients with confirmed diagnosis and smoking status data are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab | Overall Survival by Smoking Status | 40.9 Months |
| Former/Current Smoker | Overall Survival by Smoking Status | 15.5 Months |
Secondary
Time to Progression
Time to progression is defined as time from study entry until disease progression. Progression is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s) or unequivocal progression of existing nontarget lesions.
Time frame: Assessed every 8 weeks during treatment; after off-treatment, every 3 months for 2 years and then every 6 months for 3 years
Population: Only eligible and treated patients with confirmed diagnosis are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab | Time to Progression | 3.8 Months |
Secondary
Time to Progression by Smoking Status
Medians of time to progression by smoking status are reported.
Time frame: Progression assessed every 8 weeks during treatment; after off-treatment, every 3 months for 2 years and then every 6 months for 3 years. Smoking status evaluated at baseline
Population: Only eligible and treated patients with confirmed diagnosis and smoking status data are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab | Time to Progression by Smoking Status | 2.6 Months |
| Former/Current Smoker | Time to Progression by Smoking Status | 3.7 Months |