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

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00293332
• Other study ID #: CDR0000455640
• Secondary ID: UCSF-04652UCSF-I
• Status: Terminated
• Phase: Phase 2
• First received: February 16, 2006
• Last updated: February 8, 2011
• Start date: December 2005
• Est. completion date: April 2007

Study information

• Verified date: June 2007
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: April 2007
• Est. primary completion date: March 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Biological:
• bevacizumab
Neoadjuvant therapy with 15 mg/kg, IV on Day 1 of each 21 day cycle for the first 2 cycles.

Drug:
• carboplatin
Neoadjuvant therapy, AUC 6, IV on day 1 of each 21 day cycle for 3 cycles.
• docetaxel
Neoadjuvant therapy, 75 mg/m2, IV on day 1 of each 21 day cycle for 3 cycles.

Procedure:
• conventional surgery
Standard surgery after 3 cycles of neoadjuvant therapy with docetaxel, carboplatin, and bevacizumab. Bevacizumab is given for the first 2 cycles only.

Locations

Country	Name	City	State
United States	UCSF Comprehensive Cancer Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical response rate by CT scan after 3 courses of induction treatment		After 3 cycles of induction treatment	No
Secondary	Pathologic response rate after 3 courses of induction treatment		After 3 cycles of induction treatment	No
Secondary	Resectability rate after 3 courses of induction treatment		After 3 cycles of induction treatment	No
Secondary	Median survival at 2 years after surgery		2 years after surgery	No
Secondary	Safety after 3 courses of induction treatment		After 3 cycles of induction treatment	Yes
Secondary	Overall survival at 2 years after surgery		2 years after surgery	No
Secondary	Time to treatment failure within 2 years after surgery		2 years after surgery	No
Secondary	Correlation of serum VEGF levels prior to neoadjuvant therapy with primary and secondary objectives prior to start of induction treatment		Before induction treatment	No
Secondary	Correlation of serum VEGF expression in resected tumor with primary and secondary objectives		After surgical removal of tumor	No
Secondary	Correlation of VEGF levels measured immediately after resection and after adjuvant bevacizumab therapy with primary and secondary objectives		After resection and after adjuvant bevacizumab	No
Secondary	Assay additional downstream VEGF activation pathway markers		At any time during the study	No