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

Phase 2

Active, not recruiting

Conditions: Lung Adenocarcinoma
Lung Large Cell Carcinoma
Lung Squamous Cell Carcinoma
Minimally Invasive Lung Adenocarcinoma
Stage IIIA Lung Non-Small Cell Cancer AJCC v7
Stage IIIB Lung Non-Small Cell Cancer AJCC v7
Lung Adenosquamous Carcinoma

Interventions: Drug: Cisplatin
Biological: Bevacizumab
Drug: Docetaxel
Drug: Etoposide
Biological: Filgrastim
Biological: Pegfilgrastim
Radiation: Radiation Therapy

Registration Number: NCT00334815

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 29

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

Exclusion Criteria

Not provided

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1 (cisplatin, etoposide, radiotherapy)	Pegfilgrastim	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.
Group 2 (cisplatin, etoposide, radiotherapy, bevacizumab)	Pegfilgrastim	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 (cisplatin, etoposide, radiotherapy, bevacizumab)	Pegfilgrastim	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.
Group 1 (cisplatin, etoposide, radiotherapy)	Cisplatin	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.
Group 1 (cisplatin, etoposide, radiotherapy)	Docetaxel	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.
Group 1 (cisplatin, etoposide, radiotherapy)	Etoposide	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.
Group 1 (cisplatin, etoposide, radiotherapy)	Filgrastim	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.
Group 1 (cisplatin, etoposide, radiotherapy)	Radiation Therapy	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.
Group 2 (cisplatin, etoposide, radiotherapy, bevacizumab)	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.
Group 2 (cisplatin, etoposide, radiotherapy, bevacizumab)	Cisplatin	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 2 (cisplatin, etoposide, radiotherapy, bevacizumab)	Docetaxel	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 2 (cisplatin, etoposide, radiotherapy, bevacizumab)	Etoposide	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 2 (cisplatin, etoposide, radiotherapy, bevacizumab)	Filgrastim	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 2 (cisplatin, etoposide, radiotherapy, bevacizumab)	Radiation Therapy	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 (cisplatin, etoposide, radiotherapy, bevacizumab)	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.
Group 3 (cisplatin, etoposide, radiotherapy, bevacizumab)	Cisplatin	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.
Group 3 (cisplatin, etoposide, radiotherapy, bevacizumab)	Docetaxel	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.
Group 3 (cisplatin, etoposide, radiotherapy, bevacizumab)	Etoposide	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.
Group 3 (cisplatin, etoposide, radiotherapy, bevacizumab)	Filgrastim	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.
Group 3 (cisplatin, etoposide, radiotherapy, bevacizumab)	Radiation Therapy	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.

Primary Outcome Measures

Name	Time	Method
Adverse Events	Up to one year	Only adverse events that are possibly, probably or definitely related to study drug are reported.

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival	Disease assessments were performed every 10 weeks as long as the patient remained on protocol treatment, up to 4 years.	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.
Response Rate (Confirmed or Unconfirmed Partial Response)	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	Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions.
Overall Survival	Every week, up to 4 years	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.

Trial Locations

Locations (63): Ballad Health Cancer Care - Norton
🇺🇸
Norton, Virginia, United States
Providence Hospital
🇺🇸
Mobile, Alabama, United States
Saint Bernards Regional Medical Center
🇺🇸
Jonesboro, Arkansas, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Highlands Oncology Group - Rogers
🇺🇸
Rogers, Arkansas, United States
USC / Norris Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
Fremont - Rideout Cancer Center
🇺🇸
Marysville, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
🇺🇸
Orange, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸
Sacramento, California, United States
Providence Santa Rosa Memorial Hospital
🇺🇸
Santa Rosa, California, United States
Gene Upshaw Memorial Tahoe Forest Cancer Center
🇺🇸
Truckee, California, United States
Northbay Cancer Center
🇺🇸
Vacaville, California, United States
Rocky Mountain Regional VA Medical Center
🇺🇸
Aurora, Colorado, United States
UCHealth University of Colorado Hospital
🇺🇸
Aurora, Colorado, United States
Denver Health Medical Center
🇺🇸
Denver, Colorado, United States
University of Colorado
🇺🇸
Denver, Colorado, United States
Valley View Hospital Cancer Center
🇺🇸
Glenwood Springs, Colorado, United States
Shaw Cancer Center
🇺🇸
Edwards, Colorado, United States
Montrose Memorial Hospital
🇺🇸
Montrose, Colorado, United States
Cancer Centers of Central Florida PA
🇺🇸
Leesburg, Florida, United States
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
🇺🇸
Savannah, Georgia, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Edward Hospital/Cancer Center
🇺🇸
Naperville, Illinois, United States
HaysMed
🇺🇸
Hays, Kansas, United States
Hutchinson Regional Medical Center
🇺🇸
Hutchinson, Kansas, United States
University of Kansas Cancer Center
🇺🇸
Kansas City, Kansas, United States
Olathe Cancer Center
🇺🇸
Olathe, Kansas, United States
Salina Regional Health Center
🇺🇸
Salina, Kansas, United States
University of Kansas Health System Saint Francis Campus
🇺🇸
Topeka, Kansas, United States
LSU Health Sciences Center at Shreveport
🇺🇸
Shreveport, Louisiana, United States
Highland Clinic
🇺🇸
Shreveport, Louisiana, United States
Steward Saint Elizabeth's Medical Center
🇺🇸
Brighton, Massachusetts, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
McLaren Cancer Institute-Macomb
🇺🇸
Mount Clemens, Michigan, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
Kansas City Veterans Affairs Medical Center
🇺🇸
Kansas City, Missouri, United States
Montana Cancer Consortium NCORP
🇺🇸
Billings, Montana, United States
Benefis Sletten Cancer Institute
🇺🇸
Great Falls, Montana, United States
Arnot Ogden Medical Center/Falck Cancer Center
🇺🇸
Elmira, New York, United States
Highland Hospital
🇺🇸
Rochester, New York, United States
University of Rochester
🇺🇸
Rochester, New York, United States
Novant Health Presbyterian Medical Center
🇺🇸
Charlotte, North Carolina, United States
Southeast Clinical Oncology Research Consortium NCORP
🇺🇸
Winston-Salem, North Carolina, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Portland VA Medical Center
🇺🇸
Portland, Oregon, United States
Roper Hospital
🇺🇸
Charleston, South Carolina, United States
Wellmont Holston Valley Hospital and Medical Center
🇺🇸
Kingsport, Tennessee, United States
University of Tennessee Health Science Center
🇺🇸
Memphis, Tennessee, United States
The Don and Sybil Harrington Cancer Center
🇺🇸
Amarillo, Texas, United States
M D Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Audie L Murphy VA Hospital
🇺🇸
San Antonio, Texas, United States
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
🇺🇸
San Antonio, Texas, United States
University Hospital
🇺🇸
San Antonio, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸
San Antonio, Texas, United States
Danville Regional Medical Center
🇺🇸
Danville, Virginia, United States
MultiCare Auburn Medical Center
🇺🇸
Auburn, Washington, United States
Providence Regional Cancer System-Centralia
🇺🇸
Centralia, Washington, United States
Saint Francis Hospital
🇺🇸
Federal Way, Washington, United States
Saint Clare Hospital
🇺🇸
Lakewood, Washington, United States
Providence - Saint Peter Hospital
🇺🇸
Olympia, Washington, United States
MultiCare Good Samaritan Hospital
🇺🇸
Puyallup, Washington, United States
MultiCare Allenmore Hospital
🇺🇸
Tacoma, Washington, United States
Saint Joseph Medical Center
🇺🇸
Tacoma, Washington, United States

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

Recruitment & Eligibility

Study & Design

Trial Locations

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