Lung Cancer
Conditions
Keywords
recurrent non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer
Brief summary
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving erlotinib together with paclitaxel and carboplatin may kill more tumor cells. PURPOSE: This randomized phase II trial is studying two different doses of erlotinib when given together with paclitaxel and carboplatin to compare how well they work in treating patients with stage III, stage IV, or recurrent non-small cell lung cancer.
Detailed description
OBJECTIVES: * Compare the major objective response (complete and partial response) rates in patients with stage IIIB or IV or recurrent non-small cell lung cancer treated with high- versus low-dose erlotinib hydrochloride combined with paclitaxel and carboplatin. * Compare the duration of response, time to progression, and survival of patients treated with these regimens. * Characterize and compare the toxicities of these regimens. * Determine the recommended phase III dose of erlotinib hydrochloride. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to gender. Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive oral high-dose erlotinib hydrochloride on days 1 and 2. Patients also receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 3. * Arm II: Patients receive oral low-dose erlotinib hydrochloride, paclitaxel, and carboplatin as in arm I. In both arms, treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 58 patients will be accrued for this study.
Interventions
DRUGCarboplatin
DRUGerlotinib hydrochloride
150mg
DRUGPaclitaxel
200mg/m2
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
RANDOMIZED
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Pathologically confirmed non-small cell lung cancer * Stage IIIB or IV or recurrent disease * Measurable or evaluable indicator lesions * Must have smoked ≥ 100 cigarettes in his/her lifetime PATIENT CHARACTERISTICS: * Karnofsky performance status 70-100% * WBC ≥ 4,000/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min * Bilirubin ≤ 1.0 mg/dL * AST ≤ 2.5 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 2.5 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for ≥ 1 week after completion of study treatment * No gastrointestinal tract disease or inability to take oral medication * No prior malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the cervix * No other active medical problems, including severe infection, unstable angina, or myocardial infarction within the past 6 months * No poorly controlled hypertension or severe malnutrition * No New York Heart Association class III or IV congestive heart failure or serious cardiac arrhythmia requiring medication except chronic atrial arrhythmia (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia) PRIOR CONCURRENT THERAPY: * At least 3 weeks since prior radiotherapy to major bone marrow-containing sites * No prior chemotherapy for advanced non-small cell lung cancer * No prior agents directed at the epidermal growth factor receptor (EGFR)/HER axis (e.g., gefitinib, cetuximab, or trastuzumab \[Herceptin®\]) * No prior surgical procedure resulting in abnormal absorption of oral medications * No concurrent surgical resection, palliative radiotherapy, or hormonal therapy * No other concurrent anticancer therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | after 6 cycles of chemotherapy | Percentage of patients who experienced complete or partial response as defined by RECIST |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression | after cycle 6 of chemotherapy | Median number of months until disease progression |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 150 PRE Erlotinib 150mg on days 1 and 2 of a 21 day cycle and Carboplatin AUC6 and Paclitaxel 200 mg/m2 | 28 |
| 1,500 PRE Erlotinib 1500mg on Days 1 and 2 of a 21 day cycle and Carboplatin AUC6 and Paclitaxel 200mg/m2 | 29 |
| 1,500 POST Carboplatin AUC6, Paclitaxel 200 mg/m2 followed by Erlotinib 1500mg days 2 and 3. | 29 |
| Total | 86 |
Baseline characteristics
| Characteristic | 1,500 PRE | 1,500 POST | 150 PRE | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 15 Participants | 15 Participants | 14 Participants | 44 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 14 Participants | 14 Participants | 42 Participants |
| Age, Continuous | 62 years | 62 years | 68 years | 64 years |
| Region of Enrollment United States | 29 Participants | 29 Participants | 28 Participants | 86 Participants |
| Sex: Female, Male Female | 13 Participants | 15 Participants | 15 Participants | 43 Participants |
| Sex: Female, Male Male | 16 Participants | 14 Participants | 13 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 28 | 2 / 29 | 2 / 29 |
| serious Total, serious adverse events | 5 / 28 | 9 / 29 | 8 / 29 |
Outcome results
Primary
Overall Response Rate
Percentage of patients who experienced complete or partial response as defined by RECIST
Time frame: after 6 cycles of chemotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 150 PRE | Overall Response Rate | 18 percentage of participants |
| 1,500 PRE | Overall Response Rate | 34 percentage of participants |
| 1,500 POST | Overall Response Rate | 28 percentage of participants |
Secondary
Time to Progression
Median number of months until disease progression
Time frame: after cycle 6 of chemotherapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 150 PRE | Time to Progression | 4 months |
| 1,500 PRE | Time to Progression | 4 months |
| 1,500 POST | Time to Progression | 5 months |