Lung Cancer
Conditions
Keywords
stage IA non-small cell lung cancer, stage IB non-small cell lung cancer, stage IIA non-small cell lung cancer, adenocarcinoma of the lung, adenosquamous cell lung cancer, bronchoalveolar cell lung cancer, large cell lung cancer, squamous cell lung cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as vinorelbine, cisplatin, docetaxel, gemcitabine, and pemetrexed disodium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sometimes after surgery, the tumor may not need more treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether chemotherapy is more effective than observation in treating patients who have undergone surgery for stage I non-small cell lung cancer. PURPOSE: This randomized phase III trial is studying four chemotherapy regimens to see how well they work compared with observation in treating patients with early stage non-small cell lung cancer.
Detailed description
OBJECTIVES: Primary * To determine the potential overall survival benefit of adjuvant chemotherapy in patients with early stage non-small cell lung cancer (NSCLC) randomized to chemotherapy compared to those randomized to the present standard of care (observation). * To collect and process high-quality fresh frozen lung cancer tumor tissue for gene expression array generation from multiple institutions. Secondary * To evaluate selected genomic-based lung cancer prognostic models using data from the patients randomized to observation after resection. * To characterize the rate of chemotherapy toxicity for the different chemotherapy treatment regimens. * To assess quality of life (QOL) in early stage patients periodically after resection for NSCLC. * To examine the impact of chemotherapy on QOL for patients receiving chemotherapy, as compared to patients in the observation arm. OUTLINE: This is a multicenter study. Patients are stratified according to pathologic stage (I vs II) and ECOG performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms within 12 weeks after surgery. All patients undergo complete resection of disease (i.e., lobectomy, sleeve lobectomy, bi-lobectomy, or pneumonectomy, but not segmentectomy or wedge resection). * Arm I: Patients receive 1 of 3 chemotherapy regimens. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. * Regimen 1: Patients receive vinorelbine ditartrate IV over 10 minutes on days 1 and 8 and cisplatin IV over 60 minutes on day 1. * Regimen 2: Patients receive docetaxel IV over 60 minutes and cisplatin IV over 60 minutes on day 1. * Regimen 3: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV over 60 minutes on day 1. * Regimen 4: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 60 minutes on day 1. * Arm II: Patients receive standard care (observation). Tissue obtained at surgery is examined by RNA microarray analysis. A Lung Metagene Score (LMS) is determined for each patient and correlated with survival and response. After completion of study treatment, patients are followed every 6 months for 5 years and then once a year for 7 years.
Interventions
DRUGcisplatin
Given IV
DRUGdocetaxel
Given IV
DRUGgemcitabine hydrochloride
Given IV
DRUGpemetrexed disodium
Given IV
DRUGvinorelbine tartrate
Given IV
PROCEDUREstandard follow-up care
Standard care
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed non-small cell lung cancer * Any variant allowed (e.g., pure or mixed bronchioloalveolar carcinoma or adenosquamous cell carcinoma) * Primary tumor must be T1a, T1b, T2a, or T2b by AJCC 7.0 * No status * Tumor measuring ≥ 2.0 cm but ≤ 7.0 cm in diameter by CT scan * The mass must have a source document to verify tumor size in the greatest dimension, which includes a CT scan report, a clinic note from the enrolling physician, and/or a printed image with caliper measurements on the lung mass * Node-negative disease * Evidence of hilar or mediastinal node involvement by chest CT scan (\> 1 cm diameter) must be assessed with mediastinoscopy, endo-esophageal ultrasound with biopsy, endo-bronchial ultrasound, bronchoscopy, or mediastinal nodal sampling before or at time of thoracotomy * No locally advanced or metastatic disease PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * Granulocytes ≥ 1,500/μL * Platelet count ≥ 100,000/μL * Bilirubin ≤ 1.5 mg/dL * AST \< 1.5 times upper limit of normal (ULN) * Serum creatinine ≤ 1.5 times ULN * Not pregnant or nursing * Fertile patients must use effective contraception * No history of prior or concurrent malignancy, except curatively treated carcinoma in situ of the cervix, basal cell or squamous cell carcinoma of the skin, surgically treated in situ carcinoma of the breast, or other cancer for which the patient has been disease-free for 3 years PRIOR CONCURRENT THERAPY: * More than 3 years since prior cytotoxic or anticancer treatment * No concurrent treatment with hormones or other chemotherapeutic agents, except steroids given for adrenal failure, hormone administered for nondisease-related conditions (e.g., insulin for diabetes), or intermittent use of dexamethasone as an antiemetic * No concurrent thoracic radiotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 12 years | Overall survival (OS) is defined as the time between formal registration and death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method. |
Countries
Australia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Chemotherapy) Patients receive cisplatin 75 mg/m\^2 by IV on day 1 and vinorelbine ditartrate 30 mg/m\^2 by IV on days 1 and 8 OR docetaxel 75 mg/m\^2 by IV and cisplatin 75 mg/m\^2 by IV on day 1 OR gemcitabine hydrochloride 1200 mg/m\^2 by IV on days 1 and 8 and cisplatin 75 mg/m\^2 by IV on day 1 OR pemetrexed disodium 500 mg/m\^2 by IV and 75 mg/m\^2 by cisplatin IV on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. | 17 |
| Arm II (Observation) Patients receive standard care (observation). | 17 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 11 | 0 |
Baseline characteristics
| Characteristic | Arm I (Chemotherapy) | Total | Arm II (Observation) |
|---|---|---|---|
| Age, Continuous | 67 years | 67 years | 63 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 30 Participants | 15 Participants |
| Region of Enrollment United States | 17 participants | 34 participants | 17 participants |
| Sex: Female, Male Female | 9 Participants | 19 Participants | 10 Participants |
| Sex: Female, Male Male | 8 Participants | 15 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 5 / 8 |
| serious Total, serious adverse events | 0 / 0 | 2 / 8 |
Outcome results
Primary
Overall Survival
Overall survival (OS) is defined as the time between formal registration and death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method.
Time frame: Up to 12 years
Population: Study terminated prematurely with 34 participants recruited. Per protocol, 338 events were needed to conduct the primary analysis; therefore, the planned analyses was not performed due to a lack of events and a termination of data collection.