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

Lung Adenocarcinoma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00334815
• Other study ID #: NCI-2009-01097
• Secondary ID: NCI-2009-01097SW
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 15, 2006
• Est. completion date: February 22, 2025

Study information

• Verified date: February 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 29
• Est. completion date: February 22, 2025
• Est. primary completion date: July 1, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of Lung
• Adenocarcinoma, Bronchiolo-Alveolar
• Carcinoma
• Carcinoma, Adenosquamous
• Carcinoma, Large Cell
• Lung Adenocarcinoma
• Lung Adenosquamous Carcinoma
• 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

Intervention

Biological:
• Bevacizumab
Given IV

Drug:
• Cisplatin
Given IV
• Docetaxel
Given IV
• Etoposide
Given IV

Biological:
• Filgrastim
Given SC
• Pegfilgrastim
Given SC

Radiation:
• Radiation Therapy
Undergo thoracic radiotherapy

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events	Only adverse events that are possibly, probably or definitely related to study drug are reported.	Up to one year
Secondary	Progression-free Survival	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.	Disease assessments were performed every 10 weeks as long as the patient remained on protocol treatment, up to 4 years.
Secondary	Overall Survival	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.	Every week, up to 4 years
Secondary	Response Rate (Confirmed or Unconfirmed Partial Response)	Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions.	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