I. Compare overall survival of patients with completely resected stage IB (tumors ≥ 4cm)-IIIA non-small cell lung cancer treated with adjuvant chemotherapy with or without bevacizumab.
I. Compare disease-free survival of patients treated with these regimens. II. Compare the toxicity of these regimens in these patients. III. Perform analyses of tissue and blood to establish factors that predict clinical outcome in patients treated with these regimens.
IV. Determine whether smoking status is linked to outcome in these patients.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to type of chemotherapy (cisplatin/vinorelbine ditartrate vs cisplatin/docetaxel vs cisplatin/gemcitabine hydrochloride vs cisplatin/pemetrexed disodium), stage (IB vs II vs IIIA [N2] vs IIIA [T3, N1]), histology (squamous cell vs other), and gender. Patients are randomized to 1 of 2 treatment arms.
ARM I (adjuvant chemotherapy without bevacizumab): Patients receive 1 of 4 chemotherapy regimens.
REGIMEN 1: Patients receive vinorelbine ditartrate IV over 10 minutes on days 1 and 8 and cisplatin IV over 60 minutes on day 1 immediately following vinorelbine ditartrate administration.
REGIMEN 2: Patients receive docetaxel IV over 1 hour on day 1 and cisplatin over 1 hour on day 1 immediately following docetaxel administration.
REGIMEN 3: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV over 60 minutes on day 1 immediately following gemcitabine administration.
REGIMEN 4 (non-squamous histology only): Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 1 hour on day 1 immediately following pemetrexed disodium administration.
In all regimens, treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
ARM II (adjuvant chemotherapy with bevacizumab): Patients receive chemotherapy as in arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab repeats every 21 days for up to 1 year. Patients complete smoking status questionnaires at baseline and then every 3 months during study treatment.
After completion of study treatment, patients are followed periodically for 10 years.
- Diagnosis of stage IB-IIIA (T2-3 N0, T1-3 N1, T1-3 N3) non-small cell lung cancer (NSCLC)
- Patients with stage IB disease must have tumors measuring ≥ 4 cm
- No non-squamous cell histology (for patient assigned to receive the pemetrexed disodium and cisplatin therapy)
- Must have undergone complete resection of NSCLC within the past 6-12 weeks
- Accepted types of resection include any of the following:
- Sleeve lobectomy
- No resection by segmentectomy or wedge resection
- Mediastinal lymph node sampling at specific levels is required pre-operatively (mediastinoscopy) or intraoperatively (level 7 for right-sided tumors or level 7 and 5 and/or 6 for left sided tumors)
- ECOG performance status 0-1
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- INR ≤ 1.5 OR INR ≤ 3.0 with therapeutic anticoagulation
- PTT normal OR PTT ≤ 1.5 times upper limit of normal (ULN) for patients on therapeutic anticoagulation
- Bilirubin ≤ 1.5 mg/dL
- AST and ALT < 5 times ULN
- Creatinine ≤ 1.5 times ULN
- Creatinine clearance ≥ 45 mL/min (for patient assigned to receive the pemetrexed disodium and cisplatin therapy)
- If urine protein: creatinine ratio > 0.5, then urine protein must be < 1,000 mg by 24-hour urine collection
- No other cancer within the past 5 years except in situ carcinoma of the cervix or completely resected nonmelanoma skin cancer
- Known history of myocardial infarction or other evidence of arterial thrombotic disease (angina) allowed if there is no evidence of active disease within the past 12 months
- No history of cerebrovascular accident or transient ischemic attack
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 6 months after completion of study treatment
- No clinically significant ongoing, active, or serious infection, symptomatic or uncontrolled congestive heart failure or cardiac arrhythmia, psychiatric illness or social situation, or any other medical condition that would preclude study compliance
- No history of bleeding diathesis or coagulopathy
- Systolic blood pressure (BP) ≤ 150 and diastolic BP ≤ 90 within the past 28days
- Patients with known hypertension on a stable regimen of antihypertensive therapy allowed
- No serious nonhealing wound, ulcer, or bone fracture
- No significant traumatic injury within the past 28 days
- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
- No ongoing postoperative hemoptysis (i.e., bright red blood of ≥ ½ teaspoon
- Recovered from prior surgery
- At least 7 days since prior aspirin or non-steroidal anti-inflammatory agents (NSAIDS), dipyridamole (Persantine), ticlopine (Ticlid),clopidogrel (Plavix) and/or cilostazol (Pletal)
- No prior systemic chemotherapy
- Prior methotrexate given in low doses for non-malignant conditions with the last dose ≥ 2 weeks ago is allowed
- Other low-dose chemotherapeutics for non-malignant conditions may be allowed after review by the study chair
- No hormonal cancer therapy or radiotherapy as cancer treatment within the past 5years
- Prior surgery, biologic therapy, hormonal therapy, or radiotherapy for a malignancy diagnosed > 5 years prior to study entry that is now considered cured allowed
- No major surgery or open biopsy within the past 28 days
- No anticipated major surgery during course of treatment
- No core biopsy within the past 7 days
- Concurrent therapeutic anticoagulation therapy allowed
- No concurrent aminoglycoside antibiotics
- No concurrent growth factors
Last updated: 03/18/2013
NCT ID: NCT00324805