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

NCT ID: NCT00369551

Last Updated: 2014-03-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-30

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.

Detailed Description

PRIMARY OBJECTIVES:

I. Assess the feasibility of administering bevacizumab, paclitaxel, carboplatin, and chest radiotherapy in patients with locally advanced non-small cell lung cancer.

II. 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.

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.

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

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

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

3-dimensional conformal radiation therapy

Intervention Type: RADIATION

Undergo 3-dimensional conformal radiation therapy

paclitaxel

Intervention Type: DRUG

Given IV

bevacizumab

Intervention Type: BIOLOGICAL

Given IV

carboplatin

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

3-dimensional conformal radiation therapy

Undergo 3-dimensional conformal radiation therapy

Intervention Type: RADIATION

paclitaxel

Given IV

Intervention Type: DRUG

bevacizumab

Given IV

Intervention Type: BIOLOGICAL

carboplatin

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

3D conformal radiation therapy; 3D-CRT; Anzatax; Asotax; TAX; Taxol; anti-VEGF humanized monoclonal antibody; anti-VEGF monoclonal antibody; Avastin; rhuMAb VEGF; Carboplat; CBDCA; JM-8; Paraplat; Paraplatin

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Everett Vokes

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

Locations

University of Chicago

Chicago, Illinois, United States

Countries

United States

Other Identifiers

NCI-2012-02718

Identifier Type: REGISTRY

Identifier Source: secondary_id

UCCRC-14576A

Identifier Type: -

Identifier Source: secondary_id

CDR0000491998

Identifier Type: -

Identifier Source: secondary_id

NCI-7213

Identifier Type: -

Identifier Source: secondary_id

14576A

Identifier Type: OTHER

Identifier Source: secondary_id

7213

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA014599

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62201

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-02718

Identifier Type: -

Identifier Source: org_study_id