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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

Information source: National Cancer Institute (NCI)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: 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

Intervention: cisplatin (Drug); etoposide (Drug); radiation therapy (Radiation); bevacizumab (Biological); docetaxel (Drug); filgrastim (Biological); pegfilgrastim (Biological)

Phase: N/A

Status: Active, not recruiting

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
Antoinette Wozniak, Principal Investigator, Affiliation: Southwest Oncology Group

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 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.

Clinical Details

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

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Incidence of grade 4 or higher hemorrhage

Secondary outcome:

Progression-free survival

Overall survival

Response rate (confirmed, unconfirmed, partial, and complete)

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Locations and Contacts

Gulf Coast MBCCOP, Mobile, Alabama 36604, United States

Providence Hospital, Mobile, Alabama 36608, United States

Saint Bernards Regional Medical Center, Jonesboro, Arkansas 72401, United States

University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States

Highlands Oncology Group-Rogers, Rogers, Arkansas 72758, United States

Northbay Cancer Center, Fairfield, California 94533, United States

Fremont - Rideout Cancer Center, Marysville, California 95901, United States

Santa Rosa Memorial Hospital, Sana Rosa, California 95405, United States

Tahoe Forest Cancer Center, Truckee, California 96161, United States

University of Colorado Cancer Center - Anschutz Cancer Pavilion, Aurora, Colorado 80045, United States

Denver Health Medical Center, Denver, Colorado 80204, United States

Denver Veterans Administration Medical Center, Denver, Colorado 80220, United States

The Shaw Regional Cancer Center, Edwards, Colorado 81632, United States

Valley View Hospital Cancer Center, Glenwood Springs, Colorado 81601, United States

Montrose Memorial Hospital, Montrose, Colorado 81401, United States

Cancer Centers of Central Florida PA, Leesburg, Florida 34788, United States

Loyola University Medical Center, Maywood, Illinois 60153, United States

Edward Hospital/Cancer Center, Naperville, Illinois 60540, United States

Hays Medical Center, Hays, Kansas 67601, United States

Promise Regional Medical Center-Hutchinson, Hutchinson, Kansas 65702, United States

Olathe Cancer Center, Olathe, Kansas 66061, United States

Salina Regional Health Center, Salina, Kansas 67401, United States

Saint Francis Hospital and Medical Center - Topeka, Topeka, Kansas 66606, United States

Highland Clinic, Shreveport, Louisiana 71105, United States

Wayne State University/Karmanos Cancer Institute, Detroit, Michigan 48201, United States

McLaren-Macomb, Mount Clemens, Michigan 48043, United States

University of Mississippi Medical Center, Jackson, Mississippi 39216, United States

Kansas City Veterans Affairs Medical Center, Kansas City, Missouri 64128, United States

Montana Cancer Consortium CCOP, Billings, Montana 59101, United States

Arnot Ogden Medical Center, Elmira, New York 14905, United States

Highland Hospital, Rochester, New York 14620, United States

University of Rochester, Rochester, New York 14642, United States

Novant Health Presbyterian Medical Center, Charlotte, North Carolina 28204, United States

Southeast Cancer Control Consortium CCOP, Winston-Salem, North Carolina 27104, United States

Portland Veterans Administration Medical Center, Portland, Oregon 97239, United States

SWOG, Portland, Oregon 97239, United States

University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States

Audie L Murphy Veterans Affairs Hospital, San Antonio, Texas 78209, United States

University Hospital, San Antonio, Texas 78229, United States

University of Texas Health Science Center, San Antonio, Texas 78229, United States

Danville Regional Medical Center, Danville, Virginia 24541, United States

Additional Information

Starting date: June 2006
Last updated: September 15, 2014

Page last updated: August 23, 2015

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