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

• Sponsor: ECOG-ACRIN Cancer Research Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00828009
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 70
• Locations: 88
• Arm: 1
• Actual Duration (Months): 101
• Patients Per Site: 0.8
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Biological: bevacizumab; Biological: Tecemotide; Drug: carboplatin; Drug: cyclophosphamide; Drug: paclitaxel; Radiation: radiotherapy	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Dec 22, 2010
• Actual Primary Completion Date: Aug 20, 2018
• Actual Study Completion Date: May 22, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Tecemotide/bevacizumab after chemoradiation Concomitant Chemoradiotherapy: Patients (pts) receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 15-30 minutes weekly for 6 weeks. Pts also receive radiotherapy 5 days a week for 6½ weeks. Pts with CR, PR, or SD proceed to consolidation chemotherapy. Consolidation chemotherapy: Pts 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 (PD) or unacceptable toxicity. Pts with CR, PR, or SD proceed to maintenance therapy. Maintenance therapy: Pts receive a single dose of cyclophosphamide IV over 15-30 minutes 3 days before the first dose of bevacizumab and tecemotide. Pts then receive bevacizumab IV over 30-90 minutes on day 1 and tecemotide 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 PD or unacceptable toxicity.

Biological: bevacizumab; IV; Other Names: NSC 704865 RhuMAb VEGF Recombinant Humanized Monoclonal Bevacizumab Antibody ; Biological: Tecemotide; Other Names: L-BLP25 ; Drug: carboplatin; IV; Other Names: CBDCA paraplatin JM-8 NSC 241240 ; Drug: cyclophosphamide; IV; Other Names: Cytoxan Neosar CTX CPM ; Drug: paclitaxel; IV; Other Names: taxol NSC #673089 ; Radiation: radiotherapy; radiotherapy is given 5 days a week for 6½ weeks during concomitant chemoradiotherapy

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients With Target Adverse Events for the Step 2 Treatment [Assessed every 3 weeks while on treatment and up to 5 years]

   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.

Secondary Outcome Measures

1. Overall Survival [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]

   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.

2. Progression-free Survival [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]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Veterans Affairs Medical Center - Palo Alto	Palo Alto	California	United States	94304
2	Stanford Cancer Center	Stanford	California	United States	94305-5824
3	Medical Center of Central Georgia	Macon	Georgia	United States	31208
4	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
5	Graham Hospital	Canton	Illinois	United States	61520
6	Memorial Hospital	Carthage	Illinois	United States	62321
7	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
8	Hematology and Oncology Associates	Chicago	Illinois	United States	60611
9	Saint Joseph Hospital	Chicago	Illinois	United States	60657
10	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
11	Eureka Community Hospital	Eureka	Illinois	United States	61530
12	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
13	Ingalls Cancer Care Center at Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
14	Mason District Hospital	Havana	Illinois	United States	62644
15	Kellogg Cancer Care Center	Highland Park	Illinois	United States	60035
16	Hinsdale Hematology Oncology Associates	Hinsdale	Illinois	United States	60521
17	Provena St. Mary's Regional Cancer Center - Kankakee	Kankakee	Illinois	United States	60901
18	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois	United States	60048
19	McDonough District Hospital	Macomb	Illinois	United States	61455
20	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois	United States	61265
21	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois	United States	60714
22	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
23	Community Cancer Center	Normal	Illinois	United States	61761
24	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
25	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
26	Proctor Hospital	Peoria	Illinois	United States	61614
27	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
28	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
29	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
30	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
31	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
32	Perry Memorial Hospital	Princeton	Illinois	United States	61356
33	Swedish-American Regional Cancer Center	Rockford	Illinois	United States	61104-2315
34	Hematology Oncology Associates - Skokie	Skokie	Illinois	United States	60076
35	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois	United States	62781-0001
36	Elkhart General Hospital	Elkhart	Indiana	United States	46515
37	Howard Community Hospital	Kokomo	Indiana	United States	46904
38	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
39	Saint Joseph Regional Medical Center	Mishawaka	Indiana	United States	46545-1470
40	Cancer Center at Ball Memorial Hospital	Muncie	Indiana	United States	47303-3499
41	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
42	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
43	McFarland Clinic, PC	Ames	Iowa	United States	50010
44	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa	United States	50325
45	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
46	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
47	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
48	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
49	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
50	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
51	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
52	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51102
53	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
54	Tufts Medical Center Cancer Center	Boston	Massachusetts	United States	02111
55	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
56	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
57	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
58	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan	United States	49085
59	Lakeside Cancer Specialists, PLLC	Saint Joseph	Michigan	United States	49085
60	Cancer Resource Center - Lincoln	Lincoln	Nebraska	United States	68510
61	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
62	Immanuel Medical Center	Omaha	Nebraska	United States	68122
63	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
64	Lakeside Hospital	Omaha	Nebraska	United States	68130
65	Creighton University Medical Center	Omaha	Nebraska	United States	68131-2197
66	Cancer Institute of New Jersey at Hamilton	Hamilton	New Jersey	United States	08690
67	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States	08903
68	Stony Brook University Cancer Center	Stony Brook	New York	United States	11794-9446
69	Mercy Cancer Center at Mercy Medical Center	Canton	Ohio	United States	44708
70	Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106-5065
71	St. Rita's Medical Center	Lima	Ohio	United States	45801
72	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania	United States	18105
73	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania	United States	17822-0001
74	PinnacleHealth Regional Cancer Center at Polyclinic Hospital	Harrisburg	Pennsylvania	United States	17110-2098
75	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania	United States	18201
76	Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
77	Lewistown Hospital	Lewistown	Pennsylvania	United States	17044
78	Pottstown Memorial Regional Cancer Center	Pottstown	Pennsylvania	United States	19464
79	Geisinger Medical Group - Scenery Park	State College	Pennsylvania	United States	16801
80	Mount Nittany Medical Center	State College	Pennsylvania	United States	16803
81	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
82	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232-6838
83	Parkland Memorial Hospital	Dallas	Texas	United States	75235
84	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75390
85	West Virginia University Health Sciences Center - Charleston	Charleston	West Virginia	United States	25304
86	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin	United States	54601
87	Regional Cancer Center at Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin	United States	53066
88	Waukesha Memorial Hospital Regional Cancer Center	Waukesha	Wisconsin	United States	53188

Sponsors and Collaborators

• ECOG-ACRIN Cancer Research Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Jyoti D. Patel, Robert H. Lurie Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 8, 2014

More Information

Publications

None provided.

• Responsible Party: ECOG-ACRIN Cancer Research Group
• ClinicalTrials.gov Identifier: NCT00828009
• Other Study ID Numbers: CDR0000632611; E6508; U10CA180794
• First Posted: Jan 23, 2009
• Last Update Posted: Nov 23, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by ECOG-ACRIN Cancer Research Group: stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; adenocarcinoma of the lung
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Paclitaxel; Cyclophosphamide; Bevacizumab; Carboplatin

Study Results

Participant Flow

Recruitment Details	E6508 was activated on December 22, 2010, suspended per protocol on January 12, 2012 for interim toxicity analysis. The study was then reactivated on October 9, 2012 to stage 2 accrual and closed to accrual on October 13, 2014.

Arm/Group Title	Tecemotide/Bevacizumab After Chemoradiation
Arm/Group Description	Concomitant Chemoradiotherapy: Patients (pts) receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 15-30 minutes weekly for 6 weeks. Pts also receive radiotherapy 5 days a week for 6½ weeks. Pts with CR, PR, or SD proceed to consolidation chemotherapy. Consolidation chemotherapy: Pts 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 (PD) or unacceptable toxicity. Pts with CR, PR, or SD proceed to maintenance therapy. Maintenance therapy: Pts receive a single dose of cyclophosphamide IV over 15-30 minutes 3 days before the first dose of bevacizumab and tecemotide. Pts then receive bevacizumab IV over 30-90 minutes on day 1 and tecemotide 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 PD or unacceptable toxicity.
Period Title: Step 1 - Chemo RT/Consolidation Chemo
STARTED	70
Started Treatment	68
COMPLETED	39
NOT COMPLETED	31
Period Title: Step 1 - Chemo RT/Consolidation Chemo
STARTED	33
COMPLETED	0
NOT COMPLETED	33

Baseline Characteristics

Arm/Group Title	Step 2 - Maintenance Therapy
Arm/Group Description	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.
Overall Participants	33
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	14 42.4%
Male	19 57.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 6.1%
Not Hispanic or Latino	31 93.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	32 97%
More than one race	0 0%
Unknown or Not Reported	1 3%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients With Target Adverse Events for the Step 2 Treatment
Description	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.
Time Frame	Assessed every 3 weeks while on treatment and up to 5 years

Outcome Measure Data

Analysis Population Description

All patients who received step 2 treatment

Arm/Group Title	Step 2 - Maintenance Therapy
Arm/Group Description	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.
Measure Participants	33
Number (80% Confidence Interval) [proportion of participants]	0.03 0.1%

2. Secondary Outcome

Title	Overall Survival
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Only eligible and treated patients are included in the analysis.

Arm/Group Title	Step 2 - Maintenance Therapy
Arm/Group Description	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.
Measure Participants	32
Median (95% Confidence Interval) [months]	42.7

3. Secondary Outcome

Title	Progression-free Survival
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Only eligible and treated patients are included in this analysis.

Arm/Group Title	Step 2 - Maintenance Therapy
Arm/Group Description	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.
Measure Participants	32
Median (95% Confidence Interval) [months]	14.9

Adverse Events

Time Frame	Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years
Arm/Group Title	Step 1 - Chemoradiation and Consolidation Chemotherapy		Step 2 - Maintenance Therapy
Arm/Group Description	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.		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.
All Cause Mortality
	Step 1 - Chemoradiation and Consolidation Chemotherapy		Step 2 - Maintenance Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/68 (70.6%)		21/33 (63.6%)
Serious Adverse Events
	Step 1 - Chemoradiation and Consolidation Chemotherapy		Step 2 - Maintenance Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/68 (57.4%)		11/33 (33.3%)
Blood and lymphatic system disorders
Anemia	3/68 (4.4%)		1/33 (3%)
Febrile neutropenia	3/68 (4.4%)		0/33 (0%)
Cardiac disorders
Atrial fibrillation	1/68 (1.5%)		0/33 (0%)
Heart failure	0/68 (0%)		1/33 (3%)
Pericardial effusion	0/68 (0%)		1/33 (3%)
Gastrointestinal disorders
Diarrhea	1/68 (1.5%)		0/33 (0%)
Esophageal pain	1/68 (1.5%)		0/33 (0%)
Esophageal ulcer	0/68 (0%)		1/33 (3%)
Esophagitis	3/68 (4.4%)		0/33 (0%)
Hemorrhoidal hemorrhage	0/68 (0%)		1/33 (3%)
Mucositis oral	1/68 (1.5%)		0/33 (0%)
Vomiting	3/68 (4.4%)		0/33 (0%)
General disorders
Death NOS	0/68 (0%)		1/33 (3%)
Fatigue	6/68 (8.8%)		0/33 (0%)
Immune system disorders
Anaphylaxis	1/68 (1.5%)		0/33 (0%)
Infections and infestations
Bronchial infection	1/68 (1.5%)		0/33 (0%)
Device related infection	1/68 (1.5%)		0/33 (0%)
Lung infection	2/68 (2.9%)		0/33 (0%)
Meningitis	1/68 (1.5%)		0/33 (0%)
Mucosal infection	1/68 (1.5%)		0/33 (0%)
Sepsis	3/68 (4.4%)		1/33 (3%)
Urinary tract infection	1/68 (1.5%)		1/33 (3%)
Injury, poisoning and procedural complications
Dermatitis radiation	1/68 (1.5%)		0/33 (0%)
Investigations
Alanine aminotransferase increased	0/68 (0%)		1/33 (3%)
Aspartate aminotransferase increased	0/68 (0%)		1/33 (3%)
Lymphocyte count decreased	7/68 (10.3%)		1/33 (3%)
Neutrophil count decreased	11/68 (16.2%)		0/33 (0%)
Platelet count decreased	3/68 (4.4%)		0/33 (0%)
Weight loss	0/68 (0%)		1/33 (3%)
White blood cell decreased	14/68 (20.6%)		0/33 (0%)
Metabolism and nutrition disorders
Anorexia	2/68 (2.9%)		0/33 (0%)
Dehydration	5/68 (7.4%)		0/33 (0%)
Hyperglycemia	1/68 (1.5%)		0/33 (0%)
Hypokalemia	1/68 (1.5%)		0/33 (0%)
Hyponatremia	1/68 (1.5%)		0/33 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/68 (1.5%)		0/33 (0%)
Myalgia	1/68 (1.5%)		0/33 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Treatment related secondary malignancy	0/68 (0%)		1/33 (3%)
Nervous system disorders
Headache	1/68 (1.5%)		0/33 (0%)
Peripheral sensory neuropathy	1/68 (1.5%)		0/33 (0%)
Syncope	1/68 (1.5%)		0/33 (0%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm	1/68 (1.5%)		0/33 (0%)
Pneumonitis	0/68 (0%)		0/33 (0%)
Vascular disorders
Flushing	1/68 (1.5%)		0/33 (0%)
Hypertension	1/68 (1.5%)		6/33 (18.2%)
Hypotension	2/68 (2.9%)		0/33 (0%)
Thromboembolic event	0/68 (0%)		1/33 (3%)
Other (Not Including Serious) Adverse Events
	Step 1 - Chemoradiation and Consolidation Chemotherapy		Step 2 - Maintenance Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	65/68 (95.6%)		32/33 (97%)
Blood and lymphatic system disorders
Anemia	39/68 (57.4%)		18/33 (54.5%)
Gastrointestinal disorders
Constipation	14/68 (20.6%)		2/33 (6.1%)
Diarrhea	15/68 (22.1%)		6/33 (18.2%)
Dry mouth	0/68 (0%)		2/33 (6.1%)
Dyspepsia	9/68 (13.2%)		2/33 (6.1%)
Dysphagia	15/68 (22.1%)		3/33 (9.1%)
Esophagitis	32/68 (47.1%)		2/33 (6.1%)
Gastroesophageal reflux disease	4/68 (5.9%)		0/33 (0%)
Mucositis oral	12/68 (17.6%)		2/33 (6.1%)
Nausea	40/68 (58.8%)		10/33 (30.3%)
Vomiting	13/68 (19.1%)		3/33 (9.1%)
General disorders
Chills	5/68 (7.4%)		4/33 (12.1%)
Fatigue	50/68 (73.5%)		26/33 (78.8%)
Fever	4/68 (5.9%)		0/33 (0%)
Flu like symptoms	0/68 (0%)		4/33 (12.1%)
Injection site reaction	0/68 (0%)		2/33 (6.1%)
Pain	6/68 (8.8%)		2/33 (6.1%)
Immune system disorders
Allergic reaction	4/68 (5.9%)		0/33 (0%)
Injury, poisoning and procedural complications
Dermatitis radiation	13/68 (19.1%)		0/33 (0%)
Investigations
Alanine aminotransferase increased	0/68 (0%)		2/33 (6.1%)
Alkaline phosphatase increased	0/68 (0%)		3/33 (9.1%)
Aspartate aminotransferase increased	0/68 (0%)		3/33 (9.1%)
Lymphocyte count decreased	8/68 (11.8%)		9/33 (27.3%)
Neutrophil count decreased	21/68 (30.9%)		0/33 (0%)
Platelet count decreased	26/68 (38.2%)		6/33 (18.2%)
Weight loss	16/68 (23.5%)		4/33 (12.1%)
White blood cell decreased	40/68 (58.8%)		10/33 (30.3%)
Metabolism and nutrition disorders
Anorexia	14/68 (20.6%)		9/33 (27.3%)
Dehydration	6/68 (8.8%)		0/33 (0%)
Hyperglycemia	4/68 (5.9%)		0/33 (0%)
Hypoalbuminemia	6/68 (8.8%)		3/33 (9.1%)
Hypokalemia	7/68 (10.3%)		3/33 (9.1%)
Hyponatremia	7/68 (10.3%)		0/33 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	11/68 (16.2%)		6/33 (18.2%)
Generalized muscle weakness	4/68 (5.9%)		0/33 (0%)
Myalgia	12/68 (17.6%)		2/33 (6.1%)
Nervous system disorders
Dizziness	4/68 (5.9%)		3/33 (9.1%)
Dysgeusia	20/68 (29.4%)		8/33 (24.2%)
Headache	7/68 (10.3%)		2/33 (6.1%)
Peripheral motor neuropathy	12/68 (17.6%)		7/33 (21.2%)
Peripheral sensory neuropathy	22/68 (32.4%)		17/33 (51.5%)
Psychiatric disorders
Insomnia	0/68 (0%)		2/33 (6.1%)
Renal and urinary disorders
Proteinuria	0/68 (0%)		6/33 (18.2%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	0/68 (0%)		2/33 (6.1%)
Cough	9/68 (13.2%)		7/33 (21.2%)
Dyspnea	10/68 (14.7%)		5/33 (15.2%)
Epistaxis	0/68 (0%)		3/33 (9.1%)
Hoarseness	0/68 (0%)		3/33 (9.1%)
Pneumonitis	0/68 (0%)		2/33 (6.1%)
Sore throat	4/68 (5.9%)		0/33 (0%)
Voice alteration	0/68 (0%)		2/33 (6.1%)
Respiratory thoracic mediastinal - Other	0/68 (0%)		2/33 (6.1%)
Skin and subcutaneous tissue disorders
Alopecia	28/68 (41.2%)		12/33 (36.4%)
Pruritus	5/68 (7.4%)		3/33 (9.1%)
Rash acneiform	0/68 (0%)		2/33 (6.1%)
Rash maculo-papular	5/68 (7.4%)		2/33 (6.1%)
Skin and subcutaneous tissue - Other	5/68 (7.4%)		0/33 (0%)
Vascular disorders
Flushing	4/68 (5.9%)		3/33 (9.1%)
Hypertension	6/68 (8.8%)		12/33 (36.4%)
Hypotension	6/68 (8.8%)		3/33 (9.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.