Clinical trial NCT00828009: BLP25 Liposome Vaccine and Bevacizumab After Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery
Official title: A Phase II Study of L-BLP25 and Bevacizumab in Unresectable Stage IIIA and IIIB Non-Squamous Non-Small Cell Lung Cancer After Definitive Chemoradiation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
adenocarcinoma of the lung
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-01-23
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Vaccines may help the body build an effective immune response 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. Drugs used in chemotherapy 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. Giving vaccine therapy together with bevacizumab after chemotherapy and radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects of giving BLP25 liposome vaccine together with bevacizumab after chemotherapy and radiation therapy in treating patients with newly diagnosed stage IIIA or stage IIIB non-small cell lung cancer that cannot be removed by surgery.

Detailed description: OBJECTIVES:

Primary

* To determine the safety of BLP25 liposome vaccine (tecemotide) and bevacizumab after definitive chemoradiotherapy and consolidation chemotherapy in patients with newly diagnosed, unresectable stage IIIA or IIIB nonsquamous cell non-small cell lung cancer.

Secondary

* To evaluate the overall survival and progression-free in patients treated with this regimen.
* To evaluate the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Step 1:

* Chemoradiotherapy: Patients receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 15-30 minutes once a week for 6 weeks. Patients also undergo concurrent definitive radiotherapy 5 days a week for 6½ weeks. Patients with complete response (CR), partial response (PR), or stable disease (SD) proceed to consolidation chemotherapy.
* Consolidation chemotherapy: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with CR, PR, or SD proceed to maintenance therapy.

Step 2:

* Maintenance therapy: Patients receive a single dose of cyclophosphamide IV over 15-30 minutes 3 days before the first dose of bevacizumab and BLP25 liposome vaccine. Patients then receive bevacizumab IV over 30-90 minutes on day 1 and BLP25 liposome vaccine subcutaneously on days 1, 8, and 15 of courses 1 and 2 and on day 1 of every other course beginning in course 4. Treatment repeats every 21 days for up to 34 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 5 years.

Eligibility criteria: Step 1 Inclusion Criteria:

* Histologically confirmed newly diagnosed nonsquamous non-small cell lung cancer (NSCLC), including the following subtypes:

  * Adenocarcinoma
  * Large cell undifferentiated
  * Bronchoalveolar cell
  * non-small cell carcinoma, not otherwise specified
* Unresectable stage IIIA or stage IIIB disease

  * Patients with stage IIIA disease with mediastinal lymph node enlargement between 1 cm and 2.0 cm on computerized tomography (CT) scan must have these nodes biopsied (pathologic confirmation) to rule out resectability
  * Metastases to contralateral mediastinal or supraclavicular nodes allowed
* Measurable or non-measurable disease, as defined by Response Evaluation Criteria in Solid Tumours (RECIST) criteria
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* White blood cell (WBC) ≥ 4,000/mm³ OR Absolute neutrophil count (ANC) ≥ 2,000/mm³
* Platelet count ≥ 140,000/mm³
* Hemoglobin ≥ 9.0 g/dL
* Total bilirubin ≤ 1.5 mg/dL
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT)+ ≤ 2.5 times upper limit of normal
* Serum creatinine ≤ 1.5 mg/mL OR creatinine clearance ≥ 45 mL/min
* Urine protein:creatinine ratio \< 1.0 by urine dipstick OR \< 1 g of protein by 24-hour urine collection
* INR ≤ 1.5 OR ≤ 3.0 if patient is on therapeutic anticoagulation
* PTT normal
* Fertile patients must use effective contraception before, during, and for ≥ 6 months after completion of bevacizumab

Step 1 Exclusion Criteria:

* Significant pleural effusion
* CNS metastases by head CT scan or MRI within the past 4 weeks
* Pregnant or breast-feeding
* Prior chemotherapy or monoclonal antibodies for other cancers within 5 years prior to registration
* Prior chemotherapy for lung cancer
* Prior chest radiotherapy
* Ongoing (lasting \> 14 days) or active infection or ongoing (lasting \> 14 days) fever within the past 6 months
* Gross hemoptysis ≥ grade 2 (defined as ≥ ½ teaspoon of bright red blood per episode) within the past 3 months
* Bleeding ≥ grade 2 or any bleeding requiring intervention
* Clinically significant cardiovascular disease
* Myocardial infarction within the past 6 months
* New York Heart Association class III-IV congestive heart failure
* Unstable angina pectoris
* Serious cardiac arrhythmia requiring medication within the past 4 weeks
* History of hypertensive crisis or hypertensive encephalopathy
* Stroke or transient ischemic attack within the past 6 months
* Peripheral vascular disease ≥ grade 2 within the past 6 months
* Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
* Psychiatric illness or social situation that would limit compliance with study requirements
* History of uncontrolled hypertension (i.e., blood pressure ≥ 150/100 mm Hg) while on stable regimen of antihypertensive therapy
* Significant traumatic injury or serious non-healing wound, ulcer, or bone fracture within the past 4 weeks
* Concurrent major surgical procedure
* Having anticipated major surgical procedure(s) during the course of the study
* Concurrent daily aspirin (\> 325 mg/day) or nonsteroidal anti-inflammatory agents (NSAIDs) known to inhibit platelet function
* Recognized immunodeficiency disease, including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia, or hereditary or congenital immunodeficiencies
* Pre-existing medical condition requiring chronic steroids or immunosuppressive therapy
* Autoimmune disease
* Known hepatitis B or C
* Immunotherapy (e.g., interferon, interleukin, sargramostim \[GM-CSF\], or filgrastim \[G-CSF\]) within 28 days prior to registration
* Prior splenectomy
* Hypersensitivity to any component of bevacizumab
* Prior core biopsy or any other minor surgical procedure, excluding the placement of a vascular access device, within 7 days prior to registration

Step 2 Inclusion Criteria:

* Serum creatinine ≤ 1.5 mg/ml or calculated creatinine clearance ≥ 45 ml/min
* Urine dipstick must be ≤ 0-1+. If urine dipstick results \> 1+, 24 hour urine for protein must be obtained. Patients must have \< 1g protein/24 hours to participate in the study
* Patient must be registered to step 2 within 28 days of completion of consolidation chemotherapy
* Patient must have met all eligibility requirements for Step 1
* Platelets ≥ 100,000/mm3

Step 2 Exclusion Criteria:

* Progressive disease or unevaluable disease per RECIST criteria upon post- consolidation chemotherapy evaluation
* Autoimmune disease

Primary outcomes:
measure: Proportion of Patients With Target Adverse Events for the Step 2 Treatment
timeFrame: Assessed every 3 weeks while on treatment and up to 5 years
Secondary outcomes:
measure: Overall Survival
timeFrame: Every 3 months for patients < 2 years from study entry, and every 6 months if patient is 2-5 years from study entry; up to 5 years
measure: Progression-free Survival
timeFrame: Every 3 months for patients < 2 years from study entry, and every 6 months if patient is 2-5 years from study entry; up to 5 years
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Veterans Affairs Medical Center - Palo Alto
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Macon
country: United States
facility: Medical Center of Central Georgia
state: Georgia
city: Bloomington
country: United States
facility: St. Joseph Medical Center
state: Illinois
city: Canton
country: United States
facility: Graham Hospital
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Hematology and Oncology Associates
state: Illinois
city: Chicago
country: United States
facility: Saint Joseph Hospital
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Institute
state: Illinois
city: Eureka
country: United States
facility: Eureka Community Hospital
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Clinic, PC
state: Illinois
city: Harvey
country: United States
facility: Ingalls Cancer Care Center at Ingalls Memorial Hospital
state: Illinois
city: Havana
country: United States
facility: Mason District Hospital
state: Illinois
city: Highland Park
country: United States
facility: Kellogg Cancer Care Center
state: Illinois
city: Hinsdale
country: United States
facility: Hinsdale Hematology Oncology Associates
state: Illinois
city: Kankakee
country: United States
facility: Provena St. Mary's Regional Cancer Center - Kankakee
state: Illinois
city: Libertyville
country: United States
facility: North Shore Oncology and Hematology Associates, Limited - Libertyville
state: Illinois
city: Macomb
country: United States
facility: McDonough District Hospital
state: Illinois
city: Moline
country: United States
facility: Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
state: Illinois
city: Niles
country: United States
facility: Cancer Care and Hematology Specialists of Chicagoland - Niles
state: Illinois
city: Normal
country: United States
facility: BroMenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center
state: Illinois
city: Ottawa
country: United States
facility: Community Hospital of Ottawa
state: Illinois
city: Pekin
country: United States
facility: Cancer Treatment Center at Pekin Hospital
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Peoria
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Peoria
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Community Hospital
state: Illinois
city: Princeton
country: United States
facility: Perry Memorial Hospital
state: Illinois
city: Rockford
country: United States
facility: Swedish-American Regional Cancer Center
state: Illinois
city: Skokie
country: United States
facility: Hematology Oncology Associates - Skokie
state: Illinois
city: Springfield
country: United States
facility: Regional Cancer Center at Memorial Medical Center
state: Illinois
city: Elkhart
country: United States
facility: Elkhart General Hospital
state: Indiana
city: Kokomo
country: United States
facility: Howard Community Hospital
state: Indiana
city: La Porte
country: United States
facility: Center for Cancer Therapy at LaPorte Hospital and Health Services
state: Indiana
city: Mishawaka
country: United States
facility: Saint Joseph Regional Medical Center
state: Indiana
city: Muncie
country: United States
facility: Cancer Center at Ball Memorial Hospital
state: Indiana
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic, PC
state: Iowa
city: Clive
country: United States
facility: Medical Oncology and Hematology Associates - West Des Moines
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at John Stoddard Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at Mercy Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Lutheran Hospital
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center - Sioux City
state: Iowa
city: Sioux City
country: United States
facility: St. Luke's Regional Medical Center
state: Iowa
city: Boston
country: United States
facility: Tufts Medical Center Cancer Center
state: Massachusetts
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeland Regional Cancer Care Center - St. Joseph
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeside Cancer Specialists, PLLC
state: Michigan
city: Lincoln
country: United States
facility: Cancer Resource Center - Lincoln
state: Nebraska
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Omaha
country: United States
facility: Immanuel Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Alegant Health Cancer Center at Bergan Mercy Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Lakeside Hospital
state: Nebraska
city: Omaha
country: United States
facility: Creighton University Medical Center
state: Nebraska
city: Hamilton
country: United States
facility: Cancer Institute of New Jersey at Hamilton
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
state: New Jersey
city: Stony Brook
country: United States
facility: Stony Brook University Cancer Center
state: New York
city: Canton
country: United States
facility: Mercy Cancer Center at Mercy Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Lima
country: United States
facility: St. Rita's Medical Center
state: Ohio
city: Allentown
country: United States
facility: Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Cancer Institute at Geisinger Health
state: Pennsylvania
city: Harrisburg
country: United States
facility: PinnacleHealth Regional Cancer Center at Polyclinic Hospital
state: Pennsylvania
city: Hazleton
country: United States
facility: Geisinger Hazleton Cancer Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Lewistown
country: United States
facility: Lewistown Hospital
state: Pennsylvania
city: Pottstown
country: United States
facility: Pottstown Memorial Regional Cancer Center
state: Pennsylvania
city: State College
country: United States
facility: Geisinger Medical Group - Scenery Park
state: Pennsylvania
city: State College
country: United States
facility: Mount Nittany Medical Center
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: Parkland Memorial Hospital
state: Texas
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Charleston
country: United States
facility: West Virginia University Health Sciences Center - Charleston
state: West Virginia
city: La Crosse
country: United States
facility: Gundersen Lutheran Center for Cancer and Blood
state: Wisconsin
city: Oconomowoc
country: United States
facility: Regional Cancer Center at Oconomowoc Memorial Hospital
state: Wisconsin
city: Waukesha
country: United States
facility: Waukesha Memorial Hospital Regional Cancer Center
state: Wisconsin
Study officials:
affiliation: Robert H. Lurie Cancer Center
name: Jyoti D. Patel
role: STUDY_CHAIR
References: