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

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00828009
• Other study ID #: CDR0000632611
• Secondary ID: E6508U10CA180794
• Status: Completed
• Phase: Phase 2
• Start date: January 17, 2011
• Est. completion date: May 22, 2019

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: May 22, 2019
• Est. primary completion date: August 20, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Biological:
• bevacizumab
IV
• Tecemotide

Drug:
• carboplatin
IV
• cyclophosphamide
IV
• paclitaxel
IV

Radiation:
• radiotherapy
radiotherapy is given 5 days a week for 6½ weeks during concomitant chemoradiotherapy

Locations

Country	Name	City	State
United States	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania
United States	McFarland Clinic, PC	Ames	Iowa
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Tufts Medical Center Cancer Center	Boston	Massachusetts
United States	Graham Hospital	Canton	Illinois
United States	Mercy Cancer Center at Mercy Medical Center	Canton	Ohio
United States	Memorial Hospital	Carthage	Illinois
United States	West Virginia University Health Sciences Center - Charleston	Charleston	West Virginia
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Saint Joseph Hospital	Chicago	Illinois
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa
United States	Parkland Memorial Hospital	Dallas	Texas
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Eureka Community Hospital	Eureka	Illinois
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Cancer Institute of New Jersey at Hamilton	Hamilton	New Jersey
United States	PinnacleHealth Regional Cancer Center at Polyclinic Hospital	Harrisburg	Pennsylvania
United States	Ingalls Cancer Care Center at Ingalls Memorial Hospital	Harvey	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania
United States	Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Kellogg Cancer Care Center	Highland Park	Illinois
United States	Hinsdale Hematology Oncology Associates	Hinsdale	Illinois
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Provena St. Mary's Regional Cancer Center - Kankakee	Kankakee	Illinois
United States	Howard Community Hospital	Kokomo	Indiana
United States	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois
United States	St. Rita's Medical Center	Lima	Ohio
United States	Cancer Resource Center - Lincoln	Lincoln	Nebraska
United States	McDonough District Hospital	Macomb	Illinois
United States	Medical Center of Central Georgia	Macon	Georgia
United States	Saint Joseph Regional Medical Center	Mishawaka	Indiana
United States	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois
United States	Cancer Center at Ball Memorial Hospital	Muncie	Indiana
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Regional Cancer Center at Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	Lakeside Hospital	Omaha	Nebraska
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Veterans Affairs Medical Center - Palo Alto	Palo Alto	California
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	Pottstown Memorial Regional Cancer Center	Pottstown	Pennsylvania
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Swedish-American Regional Cancer Center	Rockford	Illinois
United States	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan
United States	Lakeside Cancer Specialists, PLLC	Saint Joseph	Michigan
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Hematology Oncology Associates - Skokie	Skokie	Illinois
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois
United States	Stanford Cancer Center	Stanford	California
United States	Geisinger Medical Group - Scenery Park	State College	Pennsylvania
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Stony Brook University Cancer Center	Stony Brook	New York
United States	Waukesha Memorial Hospital Regional Cancer Center	Waukesha	Wisconsin
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
ECOG-ACRIN Cancer Research Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients With Target Adverse Events for the Step 2 Treatment	The study is to evaluate the safety of the combination of tecemotide immunotherapy with bevacizumab. The target adverse events for the combined treatment are as follows: grade 4-5 hemorrhage, esophagitis, fistula, platelet count decrease (thrombocytopenia), encephalitis infection, or hepatic failure episodes.	Assessed every 3 weeks while on treatment and up to 5 years
Secondary	Overall Survival	Overall survival was defined as the time from the study registration until death from any cause. Patients who were alive or lost to follow-up at the time of analysis were censored at date last known alive.	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
Secondary	Progression-free Survival	Progression-free survival was defined as the time from study registration to disease progression or death from any cause, whichever came first. If date of death was greater than 3 months after date of last disease assessment that showed progression-free, the patient was censored at the time of last disease assessment. Patients alive and without documented progression were censored at the date last known progression-free.; Progression is defined using Response Evaluation Criteria In Solid Tumors (RECIST) Criteria (version 1.1), as at least 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, the appearance of new lesions, or unequivocal progression of existing non-target lesions.	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