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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00369551
First received: August 24, 2006
Last updated: March 5, 2014
Last verified: January 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Safety and feasibility [ Time Frame: Up to 36 months ] [ Designated as safety issue: Yes ]
  • In-field toxicity, defined as bleeding or perforation of the tracheobronchial or gastrointestinal structures within the radiation field [ Time Frame: Up to 36 months ] [ Designated as safety issue: Yes ]
  • Clinical response [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
  • Correlation of levels of angiopoietin-2 and vascular endothelial growth factor receptor-2 with clinical response [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: June 2006
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00369551

Locations
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
Investigators
Principal Investigator: Everett Vokes University of Chicago
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00369551     History of Changes
Other Study ID Numbers: NCI-2012-02718, NCI-2012-02718, UCCRC-14576A, CDR0000491998, NCI-7213, 14576A, 7213, P30CA014599, N01CM62201
Study First Received: August 24, 2006
Last Updated: March 5, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Adenocarcinoma, Bronchiolo-Alveolar
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Paclitaxel
Bevacizumab
Carboplatin
Antibodies
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents

ClinicalTrials.gov processed this record on September 22, 2014