Clinical trial NCT00293332: 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
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: stage I non-small cell lung cancer
stage II non-small cell lung cancer
stage IIIA non-small cell lung cancer
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-02-17
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical response rate by CT scan after 3 courses of induction treatment
timeFrame: After 3 cycles of induction treatment
Secondary outcomes:
measure: Pathologic response rate after 3 courses of induction treatment
timeFrame: After 3 cycles of induction treatment
measure: Resectability rate after 3 courses of induction treatment
timeFrame: After 3 cycles of induction treatment
measure: Median survival at 2 years after surgery
timeFrame: 2 years after surgery
measure: Safety after 3 courses of induction treatment
timeFrame: After 3 cycles of induction treatment
measure: Overall survival at 2 years after surgery
timeFrame: 2 years after surgery
measure: Time to treatment failure within 2 years after surgery
timeFrame: 2 years after surgery
measure: Correlation of serum VEGF levels prior to neoadjuvant therapy with primary and secondary objectives prior to start of induction treatment
timeFrame: Before induction treatment
measure: Correlation of serum VEGF expression in resected tumor with primary and secondary objectives
timeFrame: After surgical removal of tumor
measure: Correlation of VEGF levels measured immediately after resection and after adjuvant bevacizumab therapy with primary and secondary objectives
timeFrame: After resection and after adjuvant bevacizumab
measure: Assay additional downstream VEGF activation pathway markers
timeFrame: At any time during the study
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Comprehensive Cancer Center
state: California
Study officials:
affiliation: University of California, San Francisco
name: Sarita Dubey, MD
role: STUDY_CHAIR
References: