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Radiation Therapy, Bevacizumab, Paclitaxel, and Carboplatin in Treating Patients With Unresectable Stage IIIB or Stage IV Non-Small Cell Lung Cancer at High Risk for Hemoptysis Caused by Bevacizumab
This study has been completed.
Sponsors and Collaborators: California Cancer Consortium
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00387374
  Purpose

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. It may also prevent hemoptysis caused by bevacizumab. 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 non-small cell lung cancer 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. Giving radiation therapy together with bevacizumab and chemotherapy may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects and how well giving radiation therapy together with bevacizumab, paclitaxel, and carboplatin works in treating patients with unresectable stage IIIB or stage IV non-small cell lung cancer at high risk for hemoptysis caused by bevacizumab.


Condition Intervention Phase
Cancer-Related Problem/Condition
Lung Cancer
Drug: bevacizumab
Drug: carboplatin
Drug: paclitaxel
Procedure: chemoprotection
Procedure: management of therapy complications
Procedure: pulmonary complications management
Procedure: radiation therapy
Phase II

MedlinePlus related topics: Cancer Lung Cancer
Drug Information available for: Carboplatin Paclitaxel Bevacizumab
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase II Study of Prophylactic Radiation Therapy for the Prevention of Hemoptysis in Advanced Non Small Cell Lung Cancer in Combination With Bevacizumab, Paclitaxel, and Carboplatin in Patients at High Risk for Bevacizumab-Associated Hemoptysis

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

Primary Outcome Measures:
  • Safety of treatment as measured by the incidence of grade 3-5 hemoptysis [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival and response rate [ Designated as safety issue: No ]

Estimated Enrollment: 72
Study Start Date: October 2006
Detailed Description:

OBJECTIVES:

Primary

  • Evaluate the safety of prophylactic chest radiotherapy, bevacizumab, paclitaxel, and carboplatin in patients with unresectable stage IIIB or IV non-small cell lung cancer at high risk for bevacizumab-associated hemoptysis.

Secondary

  • Assess progression-free survival of patients treated with this regimen.
  • Assess the rate of objective response, overall survival, time to response, and response duration in irradiated lesions and non-irradiated lesions in these patients.

OUTLINE: This is an open-label, pilot, multicenter study. Patients are assigned sequentially to 1 of 2 treatment strata.

  • Stratum I: Patients undergo prophylactic radiotherapy on days 1-5 and 8-12. Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 15. Patients also receive paclitaxel IV over 3 hours or carboplatin IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 36 (course 2).
  • Stratum II: Patients undergo prophylactic radiotherapy and receive paclitaxel and carboplatin as in stratum I. Patients also receive bevacizumab IV over 30-90 minutes on day 15 (course 1).

In both strata, treatment with paclitaxel, carboplatin, and bevacizumab repeats every 21 days for 5-6 courses in the absence of disease progression or unacceptable toxicity. Patients with complete or partial response or stable disease may continue to receive single-agent bevacizumab every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 12 months.

PROJECTED ACCRUAL: A total of 72 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

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed primary non-small cell lung cancer (NSCLC)* meeting the following criteria:

    • Squamous cell or mixed squamous-nonsquamous histology with predominant squamous component (≥ 50% squamous) with a primary, unresected endobronchial lesion

      • No small cell component
    • Centrally located primary tumor, defined by the following:

      • Primary tumor of any T stage within or touching the zone of the proximal bronchial tree

        • Zone is defined as a 3-dimensional volume with a perimeter of 2 cm in each direction around the proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus, right and left lower lobe bronchi)
        • Any disease within this volume must not invade blood vessels determined by a contrast-enhanced CT scan evaluation of the entire thorax with thin slices (≤ 5 mm) through the area of central tumor bulk (i.e., no evidence of vessel invasion radiological evaluation) NOTE: *Diagnosis based on sputum cytology must be confirmed on a second specimen
  • Stage IIIB (with malignant pleural effusion) or stage IV disease

    • Patients with stage IIIB NSCLC without an effusion are eligible if they are not candidates for combined modality therapy with curative intent (i.e., radical chemoradiotherapy)
  • At high risk for bevacizumab-associated hemoptysis

    • Hemoptysis estimated as between 2.5 mL and 10 mL (largest volume of single episode of hemoptysis) in the past 2 months
  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
  • No known brain metastases by contrast-enhanced CT scan or gadolinium-enhanced MRI of the brain
  • No clinical or radiologic evidence of an existing or impending spinal cord compression

PATIENT CHARACTERISTICS:

  • ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%
  • Life expectancy > 6 months
  • WBC ≥ 3,000/mm³
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Bilirubin normal
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN)
  • Creatinine normal OR creatinine clearance ≥ 50 mL/min
  • INR < 1.5
  • aPTT ≤ 1.5 times ULN
  • No serious medical conditions, including any of the following:

    • Unstable angina
    • Myocardial infarction or stroke (cerebrovascular accident or transient ischemic attack) within the past 6 months
    • Congestive heart failure
    • Active cardiomyopathy
    • Unstable ventricular arrhythmia
    • Symptomatic peripheral vascular disease
    • Active peptic ulcer disease
    • Uncontrolled psychotic disorders
    • Serious infections
    • Other medical conditions potentially aggravated by treatment
  • No social situation that would preclude study compliance
  • No other active malignancy
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
  • No history of bleeding diathesis or coagulopathy associated with elevated risk of bleeding
  • No uncontrolled hypertension (i.e., resting blood pressure consistently higher than systolic > 150 mm Hg and/or diastolic > 100 mm Hg with or without antihypertensive medication), history of labile hypertension, or history of poor compliance with antihypertensive medication
  • No clinically significant proteinuria (24-hour urine protein < 1,000 mg)
  • 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 28 days
  • No history of known allergy or reaction attributed to compounds of similar chemical or biological composition to bevacizumab, such as Chinese hamster ovary cell proteins or other recombinant human or humanized antibodies, Cremophor EL®, or other agents used in study treatment
  • No pre-existing peripheral neuropathy > grade 1

PRIOR CONCURRENT THERAPY:

  • No prior thoracic radiotherapy
  • At least 12 months since prior chemotherapy

    • No prior chemotherapy for advanced disease
  • No prior therapy with angiogenesis, vascular endothelial growth factor (VEGF), or VEGF-receptor inhibitors

    • Cyclooxygenase-2 inhibitors as a noncancer therapy allowed
  • At least 28 days since prior and no concurrent major surgery or open biopsy
  • At least 12 months since prior anticancer therapy for any other malignancy except basal cell carcinoma of the skin, localized prostate cancer, or in situ carcinoma of the cervix
  • At least 10 days since prior therapeutic anticoagulants or therapeutic thrombolytic agents
  • No concurrent aspirin (> 325 mg/day) or antiplatelet agents, including dipyramidole, ticlopidine, clopidogrel bisulfate, or cilostazol

    • Other concurrent nonsteroidal anti-inflammatory drugs allowed
  • No other concurrent investigational agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent anticancer agents or therapies

    • Steroids for pain, anorexia, or quality of life allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00387374

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
City of Hope Medical Group
Pasadena, California, United States, 91105
Contra Costa Regional Medical Center
Martinez, California, United States, 94553
Tower Cancer Research Foundation
Beverly Hills, California, United States, 90211
University of California Davis Cancer Center
Sacramento, California, United States, 95817
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
Veterans Affairs Outpatient Clinic - Martinez
Martinez, California, United States, 94553
United States, Pennsylvania
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
California Cancer Consortium
Investigators
Study Chair: Zelanna Goldberg, MD University of California, Davis
Investigator: Natasha Leighl, MD, FRCPC Princess Margaret Hospital, Canada
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Study ID Numbers: CDR0000504067, CCC-PHII-78, NCI-7690
Study First Received: October 12, 2006
Last Updated: October 18, 2008
ClinicalTrials.gov Identifier: NCT00387374  
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
hemoptysis
drug/agent toxicity by tissue/organ
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
squamous cell lung cancer
adenosquamous cell lung cancer

Study placed in the following topic categories:
Thoracic Neoplasms
Non-small cell lung cancer
Carboplatin
Bevacizumab
Hemoptysis
Hemorrhage
Carcinoma
Signs and Symptoms
Respiratory Tract Diseases
Lung Neoplasms
Paclitaxel
Lung Diseases
Signs and Symptoms, Respiratory
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Mitosis Modulators
Antimitotic Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Pathologic Processes
Therapeutic Uses
Tubulin Modulators
Growth Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on January 16, 2009