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Combination Chemotherapy, Radiation Therapy, and Bevacizumab in Treating Patients With Newly Diagnosed Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00334815
First received: June 7, 2006
Last updated: September 15, 2014
Last verified: April 2014
  Purpose

This clinical trial studies combination chemotherapy, radiation therapy, and bevacizumab in treating patients with newly diagnosed stage III non-small cell lung cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as cisplatin, etoposide, and docetaxel, 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. 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 more than one drug (combination chemotherapy) together with radiation therapy and bevacizumab may kill more tumor cells.


Condition Intervention
Adenocarcinoma of the Lung
Adenosquamous Cell Lung Cancer
Bronchoalveolar Cell Lung Cancer
Large Cell Lung Cancer
Squamous Cell Lung Cancer
Stage IIIA Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Drug: cisplatin
Drug: etoposide
Radiation: radiation therapy
Biological: bevacizumab
Drug: docetaxel
Biological: filgrastim
Biological: pegfilgrastim

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Trial of Cisplatin/Etoposide/Radiotherapy Followed by Consolidation Docetaxel and the Addition of Bevacizumab (NSC-704865) in Three Cohorts of Patients With Inoperable Locally Advanced Stage III Non-small Cell Lung Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Incidence of grade 4 or higher hemorrhage [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Estimated with 95% confidence interval.

  • Overall survival [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Estimated with 95% confidence interval.

  • Response rate (confirmed, unconfirmed, partial, and complete) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Estimated with 95% confidence interval.


Enrollment: 28
Study Start Date: June 2006
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1 (cisplatin, etoposide, radiotherapy)
Patients receive cisplatin IV over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Patients undergo concurrent thoracic radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47.
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Radiation: radiation therapy
Undergo thoracic radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen
Biological: pegfilgrastim
Given SC
Other Names:
  • Filgrastim SD-01
  • GCSF-SD01
  • Neulasta
  • SD-01 sustained duration G-CSF
Experimental: Group 2 (cisplatin, etoposide, radiotherapy, bevacizumab)
Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 15, 36, and 57.
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Radiation: radiation therapy
Undergo thoracic radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen
Biological: pegfilgrastim
Given SC
Other Names:
  • Filgrastim SD-01
  • GCSF-SD01
  • Neulasta
  • SD-01 sustained duration G-CSF
Experimental: Group 3 (cisplatin, etoposide, radiotherapy, bevacizumab)
Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 1, 22, and 43.
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Radiation: radiation therapy
Undergo thoracic radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen
Biological: pegfilgrastim
Given SC
Other Names:
  • Filgrastim SD-01
  • GCSF-SD01
  • Neulasta
  • SD-01 sustained duration G-CSF

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the frequency and severity of toxic effects of induction therapy comprising cisplatin, etoposide, and radiotherapy with or without bevacizumab followed by consolidation therapy comprising docetaxel and bevacizumab, in terms of grade 4 or 5 hemorrhage, in patients with newly diagnosed, unresectable, stage III non-small cell lung cancer.

SECONDARY OBJECTIVES:

I. Determine progression-free and overall survival of patients treated with these regimens.

II. Determine response (confirmed, unconfirmed, partial, and complete) in patients with measurable disease treated with these regimens.

OUTLINE: This is a pilot, multicenter study. Patients are stratified according to risk (high* vs low).

NOTE: *High-risk stratum closed to accrual as of 2/20/09.

INDUCTION THERAPY: Patients in each stratum are assigned to 1 of 3 sequential treatment groups.

GROUP 1: Patients receive cisplatin intravenously (IV) over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Patients undergo concurrent thoracic radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47.

GROUP 2: Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 15, 36, and 57.

GROUP 3: Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 1, 22, and 43.

CONSOLIDATION CHEMOTHERAPY: Beginning 3-6 weeks after completion of induction therapy, all patients receive consolidation chemotherapy comprising docetaxel IV over 1 hour and bevacizumab IV over 30-90 minutes on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 2 and continuing until blood counts recover OR pegfilgrastim SC once on day 2.

Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for up to 4 years.

  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 single, primary, bronchogenic, non-small cell lung cancer (NSCLC)

    • Newly diagnosed disease
    • Unresectable disease
    • No more than 1 parenchymal lesions on same or opposite sides of the lungs
  • Meets 1 of the following stage criteria:

    • Stage IIIA (N2) disease meeting the following criteria:

      • N2 mediastinal lymph nodes must be multiple and/or bulky on CT scan or x-ray so that the patient is not a candidate for induction chemotherapy or chemoradiotherapy followed by surgical resection
      • N2 status must be documented by ≥ 1 of the following methods:

        • Histologically or cytologically confirmed N2 disease by exploratory thoracotomy, thoracoscopy, mediastinoscopy, mediastinotomy, Chamberlain procedure, Wang needle biopsy (WNB), fine needle aspiration (FNA) under bronchoscopic or CT guidance, or any other method
        • Node positive by fludeoxyglucose-positron emission tomography (FDG-PET) scan
        • Nodes > 3 cm on CT scan
        • Paralyzed left true vocal cord with separate left lung primary distinct from anterior-posterior window nodes on CT scan
    • Stage IIIB disease meeting ≥ 1 of the following criteria:

      • Histologically or radiographically confirmed positive N3 nodes*, documented by ≥ 1 of the following methods:

        • FNA, core needle biopsy (CNB), or excisional biopsy of supraclavicular N3 nodes
        • Biopsy of contralateral mediastinal N3 nodes by mediastinoscopy, mediastinotomy, or thoracotomy
        • FNA, CNB, or WNB under CT or bronchoscopic fluoroscopic guidance of enlarged contralateral N3 mediastinal nodes
        • Contralateral mediastinal nodes > 3 cm on CT scan
        • Node positivity by FDG-PET scan
        • Right-sided primary with paralyzed left true vocal cord
      • T4 lesions of any size that invade the mediastinum, heart, great vessels, trachea, esophagus, vertebral body, or carina, documented by ≥ 1 of the following methods:

        • Written documentation of type of T4 extent if patient had a prior exploratory thoracotomy or thoracoscopy
        • T4 involvement of the trachea or carina by direct bronchoscopic visualization
        • T4 involvement of the heart, esophagus, aorta, or vertebral body by CT scan, MRI, or transesophageal ultrasound
        • T4 involvement of the mediastinum by CT scan or MRI if, in the absence of the above organ involvement, there is soft tissue extension directly into the mediastinal space**
  • Meets 1 of the following risk criteria:

    • Low risk disease, meeting the following criteria:

      • Non-squamous cell NSCLC, including adenocarcinoma, bronchoalveolar cell carcinoma, or large cell carcinoma

        • If mixed histology, the squamous cell carcinoma component must be < 50%
        • Histology or cytology from involved mediastinal or supraclavicular lymph nodes allowed if a separate distal primary lesion is clearly evident on radiographs (i.e., second biopsy not required)
      • No primary tumor with cavitation and/or tumor within 1 cm of a major vessel
      • No hemoptysis (i.e., bright red blood ≥ ½ teaspoon) in the past 28 days
    • High-risk* disease, meeting ≥ 1 of the following criteria:

      • Squamous cell NSCLC

        • If mixed histology, the squamous cell component must be ≥ 50%
      • Tumor with any histology that has cavitation or is located within 1 cm of a major vessel

        • No aortic involvement
      • Any histology and hemoptysis (i.e., bright red blood ≥ ½ teaspoon) within past 28 days
  • Measurable or nonmeasurable disease by CT scan or MRI

    • Pleural effusions, ascites, and laboratory parameters are not acceptable as the only evidence of disease
  • No pleural effusion except for small pleural effusion visible on CT scan or MRI alone
  • No pericardial effusions
  • No metastatic disease involving the contralateral chest, liver, or adrenals confirmed by CT scan of the upper abdomen or by chest CT scan with complete liver and adrenals in the report
  • Patients must be offered participation in SWOG-S9925 (Lung Cancer Specimen Repository Protocol)
  • No brain metastases by CT scan or MRI
  • No evidence of cavitation
  • Creatinine normal
  • Creatinine clearance ≥ 50 mL/min
  • FEV_1 ≥ 2.0 liters OR predicted FEV_1 of the contralateral lung > 800 mL
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Urine protein: creatinine ratio ≤ 0.5 by urinalysis OR urine protein < 1,000 mg by 24-hour urine collection
  • INR < 1.5
  • Zubrod performance status 0-1
  • No sensory neuropathy > grade 1
  • No cerebrovascular accident within the past 6 months
  • No myocardial infarction or unstable angina within the past 6 months
  • No uncontrolled hypertension
  • No New York Heart Association class II-IV congestive heart failure
  • No serious cardiac arrhythmia requiring medication
  • No clinically significant peripheral vascular disease
  • No evidence of bleeding diathesis or coagulopathy
  • No pathologic condition other than lung cancer that carries a high risk of bleeding
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • No serious, nonhealing wound, ulcer, or bone fracture
  • No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer for which the patient is currently in complete remission, or other cancer for which the patient has been disease-free for 5 years
  • Not pregnant or nursing

    • No nursing during and for ≥ 6 months after the last dose of bevacizumab
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 6 months after the last dose of bevacizumab
  • Must have pre-treatment simulation demonstrating a V20 ≤ 35% with planned radiation dose of 6,480 cGy
  • No prior surgical resection

    • Prior exploratory thoracotomy, mediastinoscopy, excisional biopsy, or similar surgery allowed for diagnosing, staging, or determining potential resectability of lung tumor
  • No prior chemotherapy or radiotherapy for lung cancer
  • No prior radiotherapy to the neck or thorax
  • At least 4 weeks since prior thoracic or other major surgery (excluding mediastinoscopy) and recovered
  • More than 7 days since prior FNA, CNB, or mediastinoscopy
  • No other concurrent anticancer therapy, including chemotherapy, radiotherapy, or biologic agents
  • No other concurrent investigational drugs
  • No concurrent major surgical procedures
  • No concurrent full-dose anticoagulants (e.g., low-molecular weight and unfractionated heparin or warfarin)

    • Low-dose warfarin (i.e., 1 mg) is allowed to prevent clotting of an infusaport or central line
  • No concurrent brachytherapy, radiopharmaceuticals, high linear energy transfer radiation (i.e., fast neutrons), particle therapy (i.e., protons, carbon, or helium), and/or altered fractionation schemes
  • No concurrent intensity-modulated radiotherapy
  • No concurrent prophylactic contralateral hilar or supraclavicular lymph node radiotherapy
  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: NCT00334815

  Show 41 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Antoinette Wozniak Southwest Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00334815     History of Changes
Other Study ID Numbers: NCI-2009-01097, NCI-2009-01097, SWOG-S0533, CDR0000472907, S0533, S0533, U10CA180888, U10CA032102
Study First Received: June 7, 2006
Last Updated: September 15, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Adenocarcinoma, Bronchiolo-Alveolar
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Antibodies
Antibodies, Monoclonal
Bevacizumab
Cisplatin
Docetaxel
Etoposide
Etoposide phosphate
Lenograstim
Adjuvants, Immunologic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors

ClinicalTrials.gov processed this record on November 25, 2014