Docetaxel, Carboplatin, and Bevacizumab in Treating Patients With Stage I, Stage II, or Stage III Non-Small Cell Lung Cancer That Can Be Removed By Surgery

Sponsor

University of California, San Francisco (Other)

Overall Status

Terminated

CT.gov ID

NCT00293332

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as docetaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Giving docetaxel and carboplatin together with bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well giving docetaxel and carboplatin together with bevacizumab works in treating patients with stage I, stage II, or stage III non-small cell lung cancer that can be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Biological: bevacizumab Drug: carboplatin Drug: docetaxel Procedure: conventional surgery	Phase 2

Detailed Description

OBJECTIVES:

Primary

Determine the clinical response rate in patients with stage IB-IIIA non-small cell lung cancer treated with neoadjuvant docetaxel, carboplatin, and bevacizumab.

Secondary

Determine the median and overall survival of patients treated with this regimen.
Determine the safety profile of this regimen.
Determine the time to treatment failure of patients treated with this regimen.
Determine the pathologic response rate and the resectability rate in patients treated with this regimen.
Correlate vascular endothelial growth factor (VEGF) levels or expression with response and survival of patients treated with this regimen.

OUTLINE: Patients receive docetaxel IV over 15-60 minutes, carboplatin IV over 30-60 minutes, and bevacizumab* IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Approximately 4-6 weeks after completion of chemotherapy, eligible patients with no distant or mediastinal disease progression undergo lobectomy, pneumonectomy, or segmentectomy with standard radical mediastinal lymph node dissection.

NOTE: *Bevacizumab is only administered during courses 1 and 2.

After completion of study treatment, patients are followed periodically for 8 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

1 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study of Neoadjuvant Therapy With Docetaxel, Carboplatin, and Bevacizumab in Patients With Resectable Early Stage Non-Small Cell Lung Cancer

Study Start Date :

Dec 1, 2005

Actual Primary Completion Date :

Mar 1, 2007

Actual Study Completion Date :

Apr 1, 2007

Outcome Measures

Primary Outcome Measures

Clinical response rate by CT scan after 3 courses of induction treatment [After 3 cycles of induction treatment]

Secondary Outcome Measures

Pathologic response rate after 3 courses of induction treatment [After 3 cycles of induction treatment]
Resectability rate after 3 courses of induction treatment [After 3 cycles of induction treatment]
Median survival at 2 years after surgery [2 years after surgery]
Safety after 3 courses of induction treatment [After 3 cycles of induction treatment]
Overall survival at 2 years after surgery [2 years after surgery]
Time to treatment failure within 2 years after surgery [2 years after surgery]
Correlation of serum VEGF levels prior to neoadjuvant therapy with primary and secondary objectives prior to start of induction treatment [Before induction treatment]
Correlation of serum VEGF expression in resected tumor with primary and secondary objectives [After surgical removal of tumor]
Correlation of VEGF levels measured immediately after resection and after adjuvant bevacizumab therapy with primary and secondary objectives [After resection and after adjuvant bevacizumab]
Assay additional downstream VEGF activation pathway markers [At any time during the study]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed non-small cell lung cancer
No squamous cell carcinoma
No histology in close proximity to a major vessel
Resectable stage IB-IIIA disease
No CNS or brain metastases

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 8.0 g/dL
Bilirubin normal
Creatinine ≤ 1.5 mg/dL
Urine protein:creatinine < 1.0
Alkaline phosphatase (AP), AST, and ALT must meet 1 of the following criteria:
AP normal AND AST and ALT ≤ 5 times upper limit of normal (ULN)
AP ≤ 2.5 times ULN AND AST and ALT ≤ 1.5 times ULN
AP ≤ 5 times ULN AND AST and ALT normal
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for at least 3 months after completion of study treatment
Adequate pulmonary and cardiovascular function to tolerate surgical resection
No cavitation or history of hemoptysis (i.e., bright red blood ≥ ½ teaspoon)
No existing peripheral neuropathy ≥ grade 1
No known history of severe hypersensitivity reaction to drugs formulated with polysorbate 80
No history of serious systemic disease, including any of the following:
Myocardial infarction within the past 6 months
Uncontrolled hypertension (i.e., blood pressure > 150/110 mm Hg on medication)
Unstable angina
New York Heart Association class II-IV congestive heart failure
Unstable symptomatic arrhythmia requiring medication
Patients with chronic atrial arrhythmia (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia) are eligible
Clinically significant peripheral vascular disease (i.e., grade II or higher)
No history of significant neurological or psychiatric condition
No known active infection within the past 14 days
No serious, nonhealing wound, ulcer, or bone fracture
No evidence of bleeding diathesis or coagulopathy
No stroke within the past 6 months
No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
No other serious illness or medical condition
No active infection
No other currently active malignancy except nonmelanoma skin cancer
Malignancies for which therapy has been completed and are considered to have ≤ 30% chance of risk of relapse are not considered active

PRIOR CONCURRENT THERAPY:

No prior chemotherapy or VEGF inhibitor
No prior (i.e., within the past 4 weeks), concurrent, or anticipated participation in another experimental drug study except a Genentech-sponsored bevacizumab cancer study
No major surgical procedure, open biopsy, or significant traumatic injury within the past 28 days
No anticipation for major surgical procedure during study treatment
No fine-needle aspiration or core biopsy within 7 days prior to study entry
No concurrent full-dose anticoagulation
No other concurrent chemotherapy, immunotherapy, radiotherapy, or investigational therapy for this cancer