Bevacizumab and Erlotinib First-Line Therapy in Advanced Non-Squamous Non-Small-Cell Lung Cancer (Stage IIIB/IV) Followed by Platinum-Based Chemotherapy at Disease Progression. A Multicenter Phase II Trial
Bevacizumab and Erlotinib First-Line Therapy in Advanced Non-Squamous Non-Small-Cell Lung Cancer (Stage IIIB/IV) Followed by Platinum-Based Chemotherapy at Disease Progression. A Multicenter Phase II Trial
RATIONALE: Monoclonal antibodies, such as bevacizumab, 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. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin, carboplatin, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with erlotinib followed by cisplatin or carboplatin and gemcitabine at disease progression may be an effective treatment for non-small cell lung cancer.
PURPOSE: This phase II trial is studying how well giving bevacizumab together with erlotinib followed by cisplatin or carboplatin and gemcitabine works in treating patients with newly diagnosed or recurrent stage IIIB or stage IV non-small cell lung cancer.
OBJECTIVES:
Primary
Secondary
Tertiary
OUTLINE: This is a multicenter, prospective, open-label study.
Patients receive bevacizumab IV over 90 minutes on day 1 and oral erlotinib hydrochloride once daily on days 1-21. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Beginning within 3 weeks of documented disease progression, patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. They also receive cisplatin IV over 1 hour or carboplatin IV over 30 minutes on day 1. Treatment with gemcitabine hydrochloride with either cisplatin or carboplatin repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline and periodically during study treatment.
After completion of study treatment, patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 101 patients will be accrued for this study.
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed non-squamous non-small cell lung cancer (NSCLC)
Meets 1 of the following staging criteria:
Stage IIIB disease, meeting both of the following criteria:
Stage IV disease
Measurable disease, defined as ≥ 1 lesion (outside of irradiated areas) that can be measured in ≥ 1 dimension as ≥ 10 mm by spiral or multi-slice CT scan or MRI
Immediate chemotherapy not clinically mandatory in the judgement of the investigator
No intrathoracic large, centrally located tumors and/or cavitary lesions invading or abutting major blood vessels
No evidence of clinically active interstitial lung disease
No small cell lung cancer (SCLC), squamous NSCLC, or combined SCLC-NSCLC tumors
No brain metastases
PATIENT CHARACTERISTICS:
WHO performance status 0-1
Hemoglobin ≥ 10 g/dL
Absolute neutrophil count ≥ 1,500/mm³
Thrombocyte count ≥ 100,000/mm³
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
ALT ≤ 2.5 times ULN (5 times ULN if liver metastases present)
Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN if bone metastases present)
Quick ≥ 70% OR INR ≤ 1.5
Creatinine ≤ 2.0 times ULN
Proteinuria ≤ 2+ by urine dipstick
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 12 months after completion of study treatment
Able to understand trial information given by the investigator and complete quality of life questionnaire
No pre-existing condition that would preclude swallowing and/or absorption of oral medication
No prior or concurrent malignancies, except for the following:
No other medical condition that would preclude study participation, including any of the following:
No clinical history of coagulopathy or thrombosis
No hemoptysis or hematemesis ≥ grade 2 (defined as bright red blood of ≥ 5 mL per episode) within the past 6 months
No known hypersensitivity to study drug(s) or to any other component of the study drugs
No significant traumatic injury within the past 28 days
No serious underlying medical condition that would impair the ability of the patient to participate in the trial or that would preclude use of study drugs
No cerebrovascular accident or other CNS bleeding within the past 6 months
PRIOR CONCURRENT THERAPY:
At least 4 weeks since prior radiotherapy and recovered
No prior chemotherapy for advanced disease
No prior endothelial growth factor and/or vascular endothelial growth factor (receptor)-targeted therapy for NSCLC
More than 28 days since prior major surgical procedure or open biopsy
More than 30 days since prior treatment in another clinical trial
No concurrent anticoagulants (e.g., phenprocoumon, acenocoumarol, or full-dose warfarin or heparin)
No concurrent full-dose continuous use of non-steroid anti-inflammatory drugs (NSAIDs)
No concurrent aspirin or clopidogrel bisulfate
No other concurrent drugs contraindicated for use with the study drugs, according to the Swissmedic-approved product information
No other concurrent experimental drugs or anticancer therapy, including chemotherapy, immunotherapy, or hormone therapy