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
August 22, 2026 updated by: National Cancer Institute (NCI)
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
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 [cancer/tumor] cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Radiation therapy uses high-energy x-rays to kill tumor cells.
Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread.
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.
Study Overview
Status
Active, not recruiting
Conditions
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.
Study Type
Interventional
Enrollment (Actual)
29
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Alabama
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Mobile, Alabama, United States, 36608
- Providence Hospital
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Arkansas
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Jonesboro, Arkansas, United States, 72401
- Saint Bernards Regional Medical Center
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Little Rock, Arkansas, United States, 72205
- University of Arkansas for Medical Sciences
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Rogers, Arkansas, United States, 72758
- Highlands Oncology Group - Rogers
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California
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Los Angeles, California, United States, 90033
- USC / Norris Comprehensive Cancer Center
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Marysville, California, United States, 95901
- Fremont - Rideout Cancer Center
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Orange, California, United States, 92868
- UC Irvine Health/Chao Family Comprehensive Cancer Center
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Sacramento, California, United States, 95817
- University of California Davis Comprehensive Cancer Center
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Santa Rosa, California, United States, 95405
- Providence Santa Rosa Memorial Hospital
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Truckee, California, United States, 96161
- Gene Upshaw Memorial Tahoe Forest Cancer Center
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Vacaville, California, United States, 95687
- Northbay Cancer Center
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Colorado
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Aurora, Colorado, United States, 80045
- Rocky Mountain Regional VA Medical Center
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Aurora, Colorado, United States, 80045
- UCHealth University of Colorado Hospital
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Denver, Colorado, United States, 80204
- Denver Health Medical Center
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Edwards, Colorado, United States, 81632
- Shaw Cancer Center
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Glenwood Springs, Colorado, United States, 81601
- Valley View Hospital Cancer Center
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Montrose, Colorado, United States, 81401
- Montrose Memorial Hospital
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Florida
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Leesburg, Florida, United States, 34788
- Cancer Centers of Central Florida PA
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Georgia
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Savannah, Georgia, United States, 31405
- Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
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Illinois
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Maywood, Illinois, United States, 60153
- Loyola University Medical Center
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Naperville, Illinois, United States, 60540
- Edward Hospital/Cancer Center
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Kansas
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Hays, Kansas, United States, 67601
- HaysMed
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Hutchinson, Kansas, United States, 67502
- Hutchinson Regional Medical Center
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Kansas City, Kansas, United States, 66160
- University of Kansas Cancer Center
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Olathe, Kansas, United States, 66061
- Olathe Cancer Center
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Salina, Kansas, United States, 67401
- Salina Regional Health Center
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Topeka, Kansas, United States, 66606
- University of Kansas Health System Saint Francis Campus
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Louisiana
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Shreveport, Louisiana, United States, 71103
- LSU Health Sciences Center at Shreveport
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Shreveport, Louisiana, United States, 71105
- Highland Clinic
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Massachusetts
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Brighton, Massachusetts, United States, 02135
- Dana-Farber Cancer Institute at Boston Medical Center - Brighton
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Michigan
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Detroit, Michigan, United States, 48201
- Wayne State University/Karmanos Cancer Institute
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Mount Clemens, Michigan, United States, 48043
- McLaren Cancer Institute-Macomb
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Mississippi
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Jackson, Mississippi, United States, 39216
- University of Mississippi Medical Center
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Missouri
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Kansas City, Missouri, United States, 64128
- Kansas City Veterans Affairs Medical Center
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Montana
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Billings, Montana, United States, 59102
- Montana Cancer Consortium NCORP
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Great Falls, Montana, United States, 59405
- Benefis Sletten Cancer Institute
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New York
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Elmira, New York, United States, 14905
- Arnot Ogden Medical Center/Falck Cancer Center
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Rochester, New York, United States, 14642
- University of Rochester
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Rochester, New York, United States, 14620
- Highland Hospital
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North Carolina
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Charlotte, North Carolina, United States, 28204
- Novant Health Presbyterian Medical Center
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Winston-Salem, North Carolina, United States, 27104
- Southeast Clinical Oncology Research Consortium NCORP
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Oregon
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Portland, Oregon, United States, 97239
- Oregon Health and Science University
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Portland, Oregon, United States, 97239
- Portland VA Medical Center
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South Carolina
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Charleston, South Carolina, United States, 29401
- Roper Hospital
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Tennessee
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Kingsport, Tennessee, United States, 37660
- Wellmont Holston Valley Hospital and Medical Center
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Memphis, Tennessee, United States, 38163
- University of Tennessee Health Science Center
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Texas
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Amarillo, Texas, United States, 79106
- The Don and Sybil Harrington Cancer Center
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Houston, Texas, United States, 77030
- UT MD Anderson Cancer Center
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San Antonio, Texas, United States, 78229
- University Hospital
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San Antonio, Texas, United States, 78229
- University of Texas Health Science Center at San Antonio
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San Antonio, Texas, United States, 78229
- Audie L Murphy VA Hospital
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Virginia
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Danville, Virginia, United States, 24541
- Danville Regional Medical Center
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Norton, Virginia, United States, 24273
- Ballad Health Cancer Care - Norton
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Washington
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Auburn, Washington, United States, 98001
- MultiCare Auburn Medical Center
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Centralia, Washington, United States, 98531
- Providence Regional Cancer System-Centralia
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Federal Way, Washington, United States, 98003
- Saint Francis Hospital
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Lakewood, Washington, United States, 98499
- Saint Clare Hospital
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Olympia, Washington, United States, 98506-5166
- Providence - Saint Peter Hospital
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Puyallup, Washington, United States, 98372
- MultiCare Good Samaritan Hospital
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Tacoma, Washington, United States, 98405
- MultiCare Allenmore Hospital
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Tacoma, Washington, United States, 98405
- Saint Joseph Medical Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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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.
|
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given SC
Other Names:
Given SC
Other Names:
Undergo thoracic radiotherapy
Other Names:
|
|
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.
|
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given SC
Other Names:
Given SC
Other Names:
Given IV
Other Names:
Undergo thoracic radiotherapy
Other Names:
|
|
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.
|
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given SC
Other Names:
Given SC
Other Names:
Given IV
Other Names:
Undergo thoracic radiotherapy
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Adverse Events
Time Frame: Up to one year
|
Only adverse events that are possibly, probably or definitely related to study drug are reported.
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Up to one year
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Progression-free Survival
Time Frame: Disease assessments were performed every 10 weeks as long as the patient remained on protocol treatment, up to 4 years.
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From date of registration to time of first documentation of progression or symptomatic deterioration, or death due to any cause.
Patients last known to be alive and progression-free are censored at date of last contact.
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Disease assessments were performed every 10 weeks as long as the patient remained on protocol treatment, up to 4 years.
|
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Overall Survival
Time Frame: Every week, up to 4 years
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From date of registration to date of death due to any cause.
Patients last known to be alive are censored at date of last contact.
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Every week, up to 4 years
|
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Response Rate (Confirmed or Unconfirmed Partial Response)
Time Frame: Response assessment occured at the end of CRT and docetaxel/bevacizumab and then every 2-3 months for 2 years and then every 6 months until 4 years after the initial registration
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Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions.
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Response assessment occured at the end of CRT and docetaxel/bevacizumab and then every 2-3 months for 2 years and then every 6 months until 4 years after the initial registration
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Antoinette J Wozniak, SWOG Cancer Research Network
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 15, 2006
Primary Completion (Actual)
July 1, 2014
Study Completion (Estimated)
February 22, 2027
Study Registration Dates
First Submitted
June 7, 2006
First Submitted That Met QC Criteria
June 7, 2006
First Posted (Estimated)
June 8, 2006
Study Record Updates
Last Update Posted (Actual)
August 26, 2026
Last Update Submitted That Met QC Criteria
August 22, 2026
Last Verified
August 1, 2026
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Site
- Neoplasms
- Neoplasms by Histologic Type
- Neoplasms, Glandular and Epithelial
- Adenocarcinoma
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Lung Neoplasms
- Carcinoma
- Adenocarcinoma of Lung
- Adenocarcinoma, Bronchiolo-Alveolar
- Peptides
- Amino Acids, Peptides, and Proteins
- Proteins
- Sulfur Compounds
- Organic Chemicals
- Therapeutics
- Hydrocarbons
- Cycloparaffins
- Hydrocarbons, Alicyclic
- Hydrocarbons, Cyclic
- Terpenes
- Biological Factors
- Carbohydrates
- Physical Phenomena
- Podophyllotoxin
- Tetrahydronaphthalenes
- Naphthalenes
- Polycyclic Aromatic Hydrocarbons
- Hydrocarbons, Aromatic
- Polycyclic Compounds
- Glucosides
- Glycosides
- Antibodies, Monoclonal, Humanized
- Antibodies, Monoclonal
- Antibodies
- Immunoglobulins
- Immunoproteins
- Blood Proteins
- Serum Globulins
- Globulins
- Inorganic Chemicals
- Chlorine Compounds
- Nitrogen Compounds
- Taxoids
- Cyclodecanes
- Diterpenes
- Elements
- Metals
- Metals, Heavy
- Intercellular Signaling Peptides and Proteins
- Immunoglobulin Isotypes
- Sulfides
- Anions
- Ions
- Electrolytes
- Hydrogen Sulfide
- Glycoproteins
- Glycoconjugates
- Platinum Compounds
- Transition Elements
- Colony-Stimulating Factors
- Hematopoietic Cell Growth Factors
- Cytokines
- Docetaxel
- Bevacizumab
- Etoposide
- Immunoglobulin G
- Cisplatin
- 1,2-diaminocyclohexaneplatinum II citrate
- Radiotherapy
- Radiation
- Disulfides
- Platinum
- Granulocyte Colony-Stimulating Factor
- Filgrastim
- pegfilgrastim
- pegylated granulocyte colony-stimulating factor
Other Study ID Numbers
- NCI-2009-01097 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- U10CA032102 (U.S. NIH Grant/Contract)
- U10CA180888 (U.S. NIH Grant/Contract)
- SWOG-S0533
- CDR0000472907
- S0533 (Other Identifier: CTEP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.