Efficacy and Safety Study of NeuVax™ (Nelipepimut-S or E75) Vaccine to Prevent Breast Cancer Recurrence
- Conditions
- Breast Cancer With Low to Intermediate HER2 Expression
- Interventions
- Biological: Leukine® (sargramostim, GM-CSF) and water for injectionBiological: NeuVax™ vaccine
- Registration Number
- NCT01479244
- Lead Sponsor
- Galena Biopharma, Inc.
- Brief Summary
Purpose of this trial:
1. To assess the efficacy and safety of NeuVax™ administered with adjuvant Leukine® (sargramostim, GM-CSF).
2. To evaluate and compare the disease free survival (DFS) in the vaccinated and control subjects.
- Detailed Description
This is a multicenter, multinational, prospective, randomized, double-blind, controlled Phase 3 study.
The subjects eligible for this trial have an early stage node-positive breast cancer. Their tumors express low or intermediate levels of the HER2 protein. NeuVax™ will be administered after completion of front-line, standard of care therapy (surgery, radiation therapy, and chemotherapy) and can be given concomitantly with physician prescribed endocrine treatment.
NeuVax™ is the immmunodominant nonapeptide derived from the extracellular domain of the HER2 protein, a well-established target for therapeutic intervention in breast carcinoma. The nelipepimut sequence stimulates specific CD8+ cytotoxic T lymphocytes (CTL) following binding to HLA-A2/A3 molecules on antigen presenting cells (APC). These activated specific CTLs recognize, neutralize and destroy through cell lysis HER2 expressing cancer cells, including occult cancer cells and micrometastatic foci. The nelipepimut immune response can also generate CTLs to other immunogenic peptides through inter- and intra-antigenic epitope spreading. Based on a successful Phase 2 trial, which achieved its primary endpoint of DFS, the Food and Drug Administration (FDA) granted NeuVax a Special Protocol Assessment (SPA) for its Phase 3 PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) study.
The active portion of the study will last three years (36 months). The follow-up will last from 5 to 10 years.
Endpoints:
1. Primary efficacy endpoint:
* 3-year DFS
2. Secondary efficacy endpoints:
* 5- and 10-year DFS
* 3-year OS
* 5- and 10-year OS
* Safety profile, and adverse events (AEs)
* Patterns of recurrence to include Time to recurrence (TTR), time to local recurrence (TTLR), time to distant recurrence (TTDR), time to bone metastases (TTBM)
Safety Assessments:
Subjects will be assessed at every study visit for the safety endpoints, AEs,vital signs, physical examinations and laboratory data; yearly follow-up of survival will include imaging studies, ECGs, MUGA or ECHO scans and concomitant medications.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 758
-
Pathological diagnosis of invasive adenocarcinoma of the breast
-
Breast cancer completely excised, or patient receiving neoadjuvant therapy prior to surgery
-
One of these 2 surgical treatments and axillary staging with sentinel lymph node dissection or axillary dissection level I/II:
- Total mastectomy-patients with a positive sentinel lymph node must have undergone a completion axillary dissection level I/II
- BCS (lumpectomy)-patients with a positive sentinel lymph node must have undergone a completion axillary dissection level I/II unless they had clinically node negative T1-T2 tumors and fewer than 3 involved lymph nodes
-
Node-positive disease
-
Primary tumor stage T1-3 at initial diagnosis
-
HER2 negative (HER2 1+ by IHC or HER2 2+ by IHC/FISH)
-
HLA-A2 or HLA-A3 haplotype
-
Completed NCCN approved neo-adjuvant/adjuvant chemotherapy or both
-
Completed radiation therapy
-
No evidence of disease
-
Able and willing (or have legal representative) to understand the study and provide consent
Key
- Bilateral breast malignancy or suspicious mass in opposite breast
- Inflammatory breast malignancy
- History of prior breast cancer, ductal carcinoma in situ
- Prior trastuzumab therapy
- New York Heart Association Stage 3 or 4 cardiac disease
- Sensory/motor neuropathy ≥ Grade 2
- Autoimmune diseases or immune deficiency disease
- Subjects on chronic steroid therapy, other immunosuppressive therapy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Leukine® Leukine® (sargramostim, GM-CSF) and water for injection Leukine® with WFI NeuVax™ NeuVax™ vaccine NeuVax™ in WFI solution with Leukine®
- Primary Outcome Measures
Name Time Method Comparison of DFS in vaccine treated patients and control patients 36 months The primary objective is to compare the DFS in subjects with operable early-stage, node-positive breast cancer who receive standard of care multimodality therapy plus NeuVax™ as the treatment group or standard of care multimodality therapy plus the vaccine adjuvant, Leukine® as the control group.
- Secondary Outcome Measures
Name Time Method Assessment of DFS and OS at 3, 5 and 10 years in vaccine and control groups, respectively; assessment of safety 3 through 10 years The secondary objectives are to evaluate the 2 groups of subjects for:
* 5- and 10-year DFS
* 3-year OS
* 5- and 10-year OS
* Time to recurrence (TTR), time to local recurrence (TTLR), time to distant recurrence (TTDR), time to bone metastases (TTBM)
* Overall safety profile and adverse events (AEs)
Trial Locations
- Locations (194)
University Hospital Hradec Kralove, Clinic of Oncology and Radiotherapy
🇨🇿Hradec Kralove, Czech Republic
Borsod-Abauj-Zemplen County Hospital and University Educational Hospital, Center for Clinical Oncology and Radiology
🇭🇺Miskolc, Hungary
Nizhny Novgorod Regional Oncology Center
🇷🇺Nizhny Novgorod, Russian Federation
Orel Oncology Center
🇷🇺Orel, Russian Federation
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Alabama Oncology
🇺🇸Bessemer, Alabama, United States
Physicians Pain Specialists of Alabama, P.C.
🇺🇸Mobile, Alabama, United States
Pain Centers Nationwide
🇺🇸Peoria, Arizona, United States
East Valley Hematology and Oncology Medical Group
🇺🇸Burbank, California, United States
Valley Pain Consultants
🇺🇸Scottsdale, Arizona, United States
Coastal Pain Research
🇺🇸Carlsbad, California, United States
Navajo Road Pain Management Center
🇺🇸El Cajon, California, United States
California Cancer Associates for Research and Excellence, Inc.
🇺🇸Fresno, California, United States
California Cancer Associates For Research and Excellence
🇺🇸Fresno, California, United States
St. Jude Medical Center, Virginia K. Crosson Cancer Center
🇺🇸Fullerton, California, United States
Interventional Pain Management
🇺🇸Irvine, California, United States
University of Southern California/Norris Cancer Hospital
🇺🇸Los Angeles, California, United States
South Orange County Surgical Medical Group
🇺🇸Laguna Hills, California, United States
Alexander Ford, MD
🇺🇸Los Angeles, California, United States
Cancer Care Institute
🇺🇸Los Angeles, California, United States
Pete J. Ruane, MD, Inc.
🇺🇸Los Angeles, California, United States
Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute
🇺🇸Los Angeles, California, United States
Pain Institute of Santa Monica
🇺🇸Santa Monica, California, United States
Stamford Hospital, Bennett Cancer Center
🇺🇸Stamford, Connecticut, United States
Randy Scharlach, MD
🇺🇸Woodland Hills, California, United States
Holy Cross Hospital-Michael & Dianne Bienes Comprehensive Cancer Center
🇺🇸Fort Lauderdale, Florida, United States
Red Rocks Center for Rehabilitation
🇺🇸Golden, Colorado, United States
Western Connecticut Health Network, Danbury Hospital
🇺🇸Danbury, Connecticut, United States
Innovative Medical Research of South Florida, Inc.
🇺🇸Aventura, Florida, United States
Pain Management Associates of CT, PC
🇺🇸Stamford, Connecticut, United States
Cancer Specialists of North Florida (ICON)
🇺🇸Jacksonville, Florida, United States
Florida Cancer Research Institute (Florida Cancer Care)
🇺🇸Plantation, Florida, United States
Florida Cancer Care
🇺🇸Plantation, Florida, United States
Northeast Georgia Cancer Care
🇺🇸Athens, Georgia, United States
Interventional Spine and Pain Management
🇺🇸Atlanta, Georgia, United States
Northwestern University Feinberg School of Medicine, Lynn Sage Comprehensive Breast Center
🇺🇸Chicago, Illinois, United States
Central Georgia Cancer Care
🇺🇸Macon, Georgia, United States
Cancer Treatment Centers of America
🇺🇸Tulsa, Oklahoma, United States
Pain Management Institute
🇺🇸Overland Park, Kansas, United States
Mary Bird Perkins Cancer Center
🇺🇸Baton Rouge, Louisiana, United States
Physiatry Consultants
🇺🇸Bay City, Michigan, United States
Michigan Interventional Pain Center
🇺🇸Brownstown, Michigan, United States
Lahey Clinic Department of Hematology and Oncology
🇺🇸Burlington, Massachusetts, United States
William Beaumont Hospital Cancer Center
🇺🇸Royal Oak, Michigan, United States
Glenn Saperstein, D.O., LLC
🇺🇸Saginaw, Michigan, United States
Advanced Physical Medicine
🇺🇸St. Clair Shores, Michigan, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Eastchester Cancer Care Center
🇺🇸Bronx, New York, United States
Upper East Side Pain Medicine, P.C.
🇺🇸New York, New York, United States
Fountain Medical Group
🇺🇸New York, New York, United States
Comprehensive Pain Management
🇺🇸Syosset, New York, United States
APWI
🇺🇸Williamsville, New York, United States
Akron General Medical Center
🇺🇸Akron, Ohio, United States
J. Fred Stoner, MD
🇺🇸New Castle, Pennsylvania, United States
Gettysburg Cancer Center
🇺🇸Gettysburgh, Pennsylvania, United States
Conemaugh Memorial Hospital-Memorial Medical Center
🇺🇸Johnstown, Pennsylvania, United States
University of Pittsburgh Medical Center (UPMC) Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Jerrold Rosenberg, MD
🇺🇸Providence, Rhode Island, United States
Progressive Pain Solutions
🇺🇸Wind Gap, Pennsylvania, United States
The West Clinic
🇺🇸Memphis, Tennessee, United States
PRIDE
🇺🇸Dallas, Texas, United States
The West Clinic Comprehensive Breast Center
🇺🇸Germantown, Tennessee, United States
UT Southwestern Medical Center / Simmons Comprehensive Cancer Center
🇺🇸Dallas, Texas, United States
Brooke Army Medical Center (now SAMMC)
🇺🇸Ft. Sam Houston, Texas, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Multicare Health System-Research Institute
🇺🇸Tacoma, Washington, United States
Central Onco Hospital
🇧🇬Plovdiv, Bulgaria
Serdika
🇧🇬Sofia, Bulgaria
Tsaritsa Yoanna - ISUL
🇧🇬Sofia, Bulgaria
Complex Oncology Center, Veliko Tarnovo
🇧🇬Tarnovo, Bulgaria
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Sveta Marina
🇧🇬Varna, Bulgaria
Health Sciences North Cancer Centre
🇨🇦Sudbury, Ontario, Canada
Sunnybrook Research Institute
🇨🇦Toronto, Ontario, Canada
Hospital Charles LeMorne
🇨🇦Greenfield Park, Quebec, Canada
Ottawa Hospital Cancer Centre
🇨🇦Ottawa, Ontario, Canada
Masaryk Memorial Cancer Institute, Comprehensive Cancer Care Clinic
🇨🇿Brno, Czech Republic
Institut de Cancérologie de l'Ouest Siet Paul Papin
🇫🇷Angers, Cedex 9, France
University Hospital Olomouc, Clinic of Oncology
🇨🇿Olomouc, Czech Republic
General University Hospital in Prague, Clinic of Oncology
🇨🇿Prague 2, Czech Republic
Centre Oscar Lambret
🇫🇷Cédex, Lille, France
Charité Campus Mitte Universitaetsmedizin-Berlin Brustzentrum/Studienzentrum
🇩🇪Berlin, Germany
Centre Antoine Lacassagne
🇫🇷Nice, France
Institut de Cancérologie de l'Ouest/René Gauducheau
🇫🇷St Herblain, Nantes Cedex, Loire-Atlantique, France
Universitätsklinikum Frankfurt, Klinik für Frauenheilkunde und Geburtshilfe
🇩🇪Frankfurt, Germany
Universität Marburg
🇩🇪Marburg, Germany
Brustzentrum Klinikum Bremen-Mitte gGmbH
🇩🇪Bremen, Germany
Universitätsklinikum Erlangen, Frauenklinik
🇩🇪Erlangen, Germany
Nationales Centrum für Tumorerkrankungen (NCT), Gynäkologische Onkologie
🇩🇪Heidelberg, Germany
Kliniken Essen Mitte, Evang. Huyssens Stiftung/Knappschaft GmbH, Klinik für Senologie/Brustzentrum
🇩🇪Essen, Germany
Universitätsklinikum Schleswig-Holstein, Campus Kiel
🇩🇪Kiel, Germany
Rotkreuzklinikum München gGmbH, Frauenklinik
🇩🇪Muenchen, Germany
Klinikum Stuttgart, Krankenhaus Bad Cannstatt, Frauenklinik
🇩🇪Stuttgart, Germany
Gemeinschaftspraxis für Innere Medizin, Haematologie und internistische Onkologie Dr. R Schlag/Dr. Schoettker
🇩🇪Wuerzburg, Germany
Klinikum Mutterhaus der Borromaeerinnen
🇩🇪Trier, Germany
Semmelweis University, Department of Diagnostic Radiology and Oncotherapy
🇭🇺Budapest, Hungary
Universitätsklinikum Münster, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe
🇩🇪Münster, Germany
Petz Aladar County Teaching Hospital, Center for Oncoradiology
🇭🇺Gyor, Hungary
Kaposi Mor County Teaching Hospital, Center for Clinical Oncology
🇭🇺Kaposvar, Hungary
Hetenyi Geza Hospital, Department of Oncology
🇭🇺Szolnok, Jasz-Nagykun-Szolnok, Hungary
Szent Margit Hospital, V. Department of Internal Medicine, Oncology
🇭🇺Budapest, Hungary
Sheba Medical Centre
🇮🇱Tel Hasomer, Ramat Gan, Israel
Kaplan Medical Centre
🇮🇱Rehovot, Israel
Rambam Health Care Campus
🇮🇱Haifa, Israel
Rabin Medical Centre
🇮🇱Petach Tikva, Israel
Polish Red Cross Marine Hospital, Department of Chemotherapy
🇵🇱Gdynia, Poland
Provincial Specialist Hospital in Wroclaw, Department of Chemotherapy
🇵🇱Kamienskiego, Wroclaw, Poland
Greater Poland Cancer Center, Department of Chemotherapy
🇵🇱Poznan, Poland
Nicolaus Copernicus Memorial Provincial Specialist Hospital in Lodz, Department of Chemotheraphy
🇵🇱Lodz, Poland
Non-Public Health Care Facility MAGODENT
🇵🇱Warsaw, Poland
Dr. Constantin Opris County Emergency Hospital, Department of Oncology
🇷🇴Baia Mare, Maramures, Romania
Magodent
🇵🇱Warsaw, Poland
"Gavril Curteanu" Municipal Clinical Hospital
🇷🇴Oradea, Bihor, Romania
Medisprof SRL, Department of Medical Oncology
🇷🇴Cluj-Napoca, Cluj, Romania
Oncology Center "Sf. Nectarie", Department of Medical Oncology
🇷🇴Craiova, Dolj County, Romania
Filantropia Clinical Hospital, Obstetrics and Gynaecology Department
🇷🇴Bucharest, Romania
Coltea Clinical Hospital, Oncology Department
🇷🇴Bucharest, Romania
"Prof. Dr. Ion Chiricuta" Institute of Oncology
🇷🇴Cluj-Napoca, Romania
Bucharest Universtiy Emergency Hosptial, Oncology Department
🇷🇴Bucharest, Romania
Iasi Regional Oncology Institute, Department of Medical Oncology
🇷🇴Iasi, Romania
Oncomed SRL, Department of Medical Oncology
🇷🇴Timisoara, Romania
Oncology Center #2, Department of Healthcare of Krasnodar Territory Administration
🇷🇺Sochi, Krasnodar, Russian Federation
Republican Oncology Center
🇷🇺Saransk, Republic of Mordovia, Russian Federation
Republican Clinical Oncoogy Center
🇷🇺Kazan, Republic of Tatarstan, Russian Federation
Arkhangelsk Clinical Oncology Center
🇷🇺Arkhangelsk, Russian Federation
Pyatigorsk Oncology Center
🇷🇺Pyatigorsk, Stavropol Region, Russian Federation
Regional Oncology Center
🇷🇺Irkutsk, Russian Federation
Sverdlovsk Regional Oncology Center
🇷🇺Ekaterinburg, Russian Federation
Ivanovo Regional Oncology Center
🇷🇺Ivanovo, Russian Federation
Clinical Oncology Center #1, Department of Healthcare of Krasnodar Territory Administration
🇷🇺Krasnodar, Russian Federation
Krasnoyarsk Kryzhanovsky Regional Oncology Center
🇷🇺Krasnoyarsk, Russian Federation
Kursk Regional Clinical Oncology Center
🇷🇺Kursk, Russian Federation
N.N. Blokhin Russian Cancer Research Center
🇷🇺Moscow, Russian Federation
N.N. Blokhin Russian Cancer Reserach Center
🇷🇺Moscow, Russian Federation
Clinical Diagnostics Center
🇺🇦Simferopol, Autonomous Republic of Crimea, Ukraine
Orenburg Regional Clinical Oncology Center
🇷🇺Orenburg, Russian Federation
Medical Institution of Ryazan Region
🇷🇺Ryazan, Russian Federation
Samara Regional Clinical Oncology Center
🇷🇺Samara, Russian Federation
Petrov Research Institute of Oncology
🇷🇺St Petersburg, Russian Federation
Leningrad Regional Oncology Center
🇷🇺St. Petersburg, Russian Federation
St. Petersburg Clinical Hospital
🇷🇺St. Petersburg, Russian Federation
Mechnikov North-Western State Medical University
🇷🇺St. Petersburg, Russian Federation
Municipal Clinical Oncology Center
🇷🇺St. Petersburg, Russian Federation
Tambov Regional Clinical Oncology Center
🇷🇺Tambov, Russian Federation
Research Institute of Oncology
🇷🇺Tomsk, Russian Federation
Bashkir State Medical University
🇷🇺Ufa, Russian Federation
Regional Clinical Oncology Center
🇷🇺Veliky Novgorod, Russian Federation
Volgograd Regional Oncology Center #3
🇷🇺Volzhskiy, Russian Federation
Kryvyi Rih Oncology Center/Dnipropetrovsk Regional Council, Department of Chemotherapy
🇺🇦Kryvyi Rih, Dnipropetrovsk Region, Ukraine
Yaroslavl Regional Oncology Center
🇷🇺Yaroslavl, Russian Federation
Chernivtsi Regional Clinical Oncology Center, Day Care Unit
🇺🇦Chernivtsi, Ukraine
Mariupol City Interdistrict Oncology Center, Surgery Department #2
🇺🇦Mariupol, Donetsk Region, Ukraine
Kharkiv Regional Clinical Oncology Center, Day Care Unit
🇺🇦Kharkiv, Kyivskyi District, Ukraine
Dnipropetrovsk City Multispecialty Clinical Hospital #4/Dnipropetrovsk Regional Council, Department of Chemotherapy
🇺🇦Dnipropetrovsk, Ukraine
Donetsk City Oncology Center
🇺🇦Donetsk, Ukraine
Donetsk Regional Antitumor Center, Oncosurgery Department #2
🇺🇦Donetsk, Ukraine
State Institution: S.P. Grigoriev Institute of Medical Radiology Under the Academy of Medical Sciences of Ukraine
🇺🇦Kharkiv, Ukraine
Public Institution: Kiev Regional Oncology Hospital within Kyiv Regional Council
🇺🇦Kiev, Ukraine
Kirovohrad Regional Oncology Center, Department of Mammology
🇺🇦Kirovohrad, Ukraine
Lviv State Regional Treatment and Diagnostics Oncology Center, Department of Chemotherapy
🇺🇦Lviv, Ukraine
Kyiv City Clinical Oncology Center, Department of Chemotherapy
🇺🇦Kyiv, Ukraine
Odesa Regional Clinical Hospital, Center for Mastology
🇺🇦Odesa, Ukraine
Zakarpattia Regional Clinical Oncology Center, Department of Chemotherapy
🇺🇦Uzhhorod, Ukraine
Vinnytsia Regional Clinical Oncology Center
🇺🇦Vinnytsia, Ukraine
Public Institution Zaporizhia Regional Clinical Oncology Center within Zaporizhia Regional Council
🇺🇦Zaporizhia, Ukraine
Macclesfield District General Hospital
🇬🇧Macclesfield, Cheshire, United Kingdom
The Royal Marsden NHS Foundation Trust
🇬🇧London, United Kingdom
Baylor College of Medicine
🇺🇸Houston, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Swedish Cancer Institute Research
🇺🇸Seattle, Washington, United States
James Cook University Hospital
🇬🇧Middlesborough, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
Academic Unit of Oncology, Nottingham University Hospital-City Campus
🇬🇧Nottingham, United Kingdom
Plymouth Oncology Centre, Derriford Hospital
🇬🇧Plymouth, United Kingdom
Weston Park Hospital
🇬🇧Sheffield, United Kingdom
Southampton General Hospital
🇬🇧Southampton, United Kingdom
University Hospital of North Staffordshire
🇬🇧Stoke on Trent, United Kingdom
Moores UC San Diego Cancer Center (UCSD)
🇺🇸San Diego, California, United States
Cancer Care Centers of South Texas
🇺🇸San Antonio, Texas, United States
Clinical Trials of Texas, Inc
🇺🇸San Antonio, Texas, United States
Cancer Center of Kansas
🇺🇸Wichita, Kansas, United States
The Christie NHS Foundation Trust
🇬🇧Withington, Manchester, United Kingdom
University of California, San Francisco (UCSF), Hellen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
OHSU Knight Cancer Institute
🇺🇸Portland, Oregon, United States
Leeds Teaching Hospitals Trust, St. James University Hospital
🇬🇧Leeds, West Yorkshire, United Kingdom
St. Alexius Medical Center, Mid Dakota Clinic, PC
🇺🇸Bismarck, North Dakota, United States
University of Colorado Cancer Center, Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
H.Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
MD Anderson Center-Orlando Health
🇺🇸Orlando, Florida, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
James Graham Brown Cancer Center, University of Louisville
🇺🇸Louisville, Kentucky, United States
Center of Cancer and Blood Disorders (VEEDA network)
🇺🇸Bethesda, Maryland, United States
Medical College of Wisconsin Department of Surgery Froedtert Hospital and Cancer Center
🇺🇸Milwaukee, Wisconsin, United States