Bevacizumab, Paclitaxel, Carboplatin, and Radiation Therapy to the Chest in Treating Patients With Locally Advanced Non-Small Cell Lung Cancer

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Terminated

CT.gov ID

NCT00369551

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

This phase I trial studies how well giving bevacizumab together with paclitaxel, carboplatin, and radiation therapy to the chest works in treating patients with locally advanced non-small cell lung cancer. 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. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving bevacizumab together with paclitaxel, carboplatin, and radiation therapy may kill more tumor cells.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Lung Bronchoalveolar Cell Lung Cancer Large Cell Lung Cancer Stage II Non-small Cell Lung Cancer Stage IIIA Non-small Cell Lung Cancer Stage IIIB Non-small Cell Lung Cancer	Radiation: 3-dimensional conformal radiation therapy Drug: paclitaxel Biological: bevacizumab Drug: carboplatin Other: laboratory biomarker analysis	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

Assess the feasibility of administering bevacizumab, paclitaxel, carboplatin, and chest radiotherapy in patients with locally advanced non-small cell lung cancer.
Characterize the toxicity of this treatment regimen. III. Assess the clinical response to this treatment regimen. IV. Correlate circulating levels of angiopoietin-2 and vascular endothelial growth factor receptor-2 with clinical response to this treatment regimen.

OUTLINE: This is an open-label, multicenter study.Induction therapy.

Consolidation therapy: Beginning 4-5 weeks after completion chemoradiotherapy, patients receive paclitaxel IV over 1 hour followed by carboplatin IV over 1 hour followed by bevacizumab IV over 30 minutes. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

After study completion, patients are followed periodically for 36 months.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Safety and Feasibility Study of Bevacizumab With Paclitaxel, Carboplatin and Chest Radiotherapy in Patients With Locally Advanced Non-Small Lung Cancer

Study Start Date :

Jun 1, 2006

Actual Primary Completion Date :

Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (paclitaxel, carboplatin, bevacizumab, radiation) Patients receive paclitaxel IV over 1 hour and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, 36, and 43 and bevacizumab IV over 30-90 minutes on days 1, 15, 29, and 43. Patients also undergo chest radiotherapy 5 days a week for 7 weeks beginning on day 1. Consolidation therapy: Beginning 4-5 weeks after completion chemoradiotherapy, patients receive paclitaxel IV over 1 hour followed by carboplatin IV over 1 hour followed by bevacizumab IV over 30 minutes. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.	Radiation: 3-dimensional conformal radiation therapy Undergo 3-dimensional conformal radiation therapy Other Names: 3D conformal radiation therapy 3D-CRT Drug: paclitaxel Given IV Other Names: Anzatax Asotax TAX Taxol Biological: bevacizumab Given IV Other Names: anti-VEGF humanized monoclonal antibody anti-VEGF monoclonal antibody Avastin rhuMAb VEGF Drug: carboplatin Given IV Other Names: Carboplat CBDCA JM-8 Paraplat Paraplatin Other: laboratory biomarker analysis Correlative studies

Arm

Intervention/Treatment

Experimental: Treatment (paclitaxel, carboplatin, bevacizumab, radiation)

Patients receive paclitaxel IV over 1 hour and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, 36, and 43 and bevacizumab IV over 30-90 minutes on days 1, 15, 29, and 43. Patients also undergo chest radiotherapy 5 days a week for 7 weeks beginning on day 1. Consolidation therapy: Beginning 4-5 weeks after completion chemoradiotherapy, patients receive paclitaxel IV over 1 hour followed by carboplatin IV over 1 hour followed by bevacizumab IV over 30 minutes. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Radiation: 3-dimensional conformal radiation therapy

Undergo 3-dimensional conformal radiation therapy

Other Names:

3D conformal radiation therapy

3D-CRT

Drug: paclitaxel

Given IV

Other Names:

Anzatax

Asotax

TAX

Taxol

Biological: bevacizumab

Given IV

Other Names:

anti-VEGF humanized monoclonal antibody

anti-VEGF monoclonal antibody

Avastin

rhuMAb VEGF

Drug: carboplatin

Given IV

Other Names:

Carboplat

CBDCA

JM-8

Paraplat

Paraplatin

Other: laboratory biomarker analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

Safety and feasibility [Up to 36 months]
In-field toxicity, defined as bleeding or perforation of the tracheobronchial or gastrointestinal structures within the radiation field [Up to 36 months]
Clinical response [Up to 36 months]
Correlation of levels of angiopoietin-2 and vascular endothelial growth factor receptor-2 with clinical response [Up to 36 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically confirmed non-small cell lung carcinoma (NSCLC) meeting the following criteria:
The following subtypes are eligible:
Adenocarcinoma (including bronchoalveolar)
Large cell carcinoma (including giant and clear cell carcinomas)
Poorly differentiated carcinoma
No squamous cell histology
Unresectable stage II-III disease
Tumor must not invade the trachea or major arterial or venous structures
Measurable or evaluable disease
Measurable disease defined as ? 1 lesion that can be accurately measured in ? 1 dimension as ? 20 mm with conventional techniques or as ? 10 mm with spiral CT scan
No evidence of CNS disease, including primary brain tumor or brain metastases
ECOG performance status (PS) 0-1 or Karnofsky PS 60-100%
Life expectancy > 6 months
Granulocyte count ? 1,500/mm³
Platelet count ? 100,000/mm³
Bilirubin < 1.25 times upper limit of normal (ULN)
AST < 2.5 times ULN
Creatinine normalOR creatinine clearance ? 60 mL/min
FEV_1 ? 1.0 liters
24-hour urine protein < 1,000 mg (for patients with urine protein:creatinine ratio [by urine analysis] > 1.0)
No hemoptysis within the past 12 months (defined as bright red blood in sputum of > 1 teaspoon)
No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
No history of allergic reactions attributed to carboplatin or taxane
No serious or nonhealing wound, ulcer, or bone fracture
No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
No significant traumatic injury within the past 14 days
No clinically significant cardiovascular disease, including any of the following:
Cerebrovascular accident within the past 6 months
Uncontrolled hypertension
Myocardial infarction or unstable angina within the past 6 months
New York Heart Association class II-IV congestive heart failure
Serious cardiac arrhythmia requiring medication
Unstable angina pectoris
Clinically significant peripheral vascular disease
No known bleeding diathesis or coagulopathy
No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
No uncontrolled intercurrent illness including, but not limited to, the following:
Ongoing or active infection
Psychiatric illness or social situations that would limit study compliance
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for ? 6 months after completion of study treatment
No HIV positivity
No prior chemotherapy
No prior epidermal growth factor receptor-targeted therapy
No prior vascular endothelial growth factor-targeted therapy
No prior chest radiotherapy
No major surgery or open biopsy within the past 14 days
No concurrent treatment with full-dose anticoagulation
Low-dose anticoagulants (e.g., warfarin) to maintain patency of central venous catheter allowed provided all of the following criteria are met:
Daily dose of warfarin < 1 mg
INR < 1.5
No other concurrent investigational agents
No concurrent major surgical procedures
No other concurrent anticancer agents or therapies
No concurrent chronic treatment with aspirin (> 325 mg daily) or nonsteroidal anti-inflammatory agents
No dexamethasone as an antiemetic during chemoradiotherapy
No colony-stimulating factors during chemoradiotherapy