Study of Glembatumumab Vedotin (CDX-011) in Patients With Metastatic, gpNMB Over-Expressing, Triple Negative Breast Cancer
- Conditions
- Metastatic gpNMB Over-expressing Triple Negative Breast Cancer
- Interventions
- Registration Number
- NCT01997333
- Lead Sponsor
- Celldex Therapeutics
- Brief Summary
The main purpose of this study is to see whether CDX-011 (glembatumumab vedotin, an antibody-drug conjugate) is effective in treating patients who have advanced Triple-Negative Breast Cancer (TNBC), and whose tumor cells make a protein called glycoprotein NMB (gpNMB), which CDX-011 binds to. The study will also further characterize the safety of CDX-011 treatment in this patient population.
- Detailed Description
CDX-011 consists of an antibody attached to a drug, monomethyl auristatin E (MMAE), that can kill cancer cells. The antibody delivers the drug to cancer cells by attaching to a protein called glycoprotein NMB (gpNMB) that is expressed on the cancer cell. The MMAE is then released inside of the cell, where it interferes with cell growth and may lead to cell death.
This study will examine the efficacy and safety of CDX-011 in patients with advanced TNBC that makes the gpNMB protein. The effect of CDX-011 will be compared to treatment with capecitabine.
Eligible patients who enroll in the study will be randomly assigned (by chance) to receive treatment with CDX-011 or with capecitabine. For every three patients enrolled, two will receive CDX-011 and one will receive treatment with capecitabine. All patients enrolled in the study will be closely monitored to determine if their cancer is responding to treatment and for any side effects that may occur.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 327
Among other criteria, patients must meet all of the following conditions to be eligible for the study:
-
Diagnosed with metastatic (i.e., cancer that has spread) TNBC
- minimal or no expression of estrogen and progesterone receptors (ER/PR) <10% of cells positive by immunohistochemistry
- HER 2 staining 0 or 1+ by IHC or copy number <4.0 signals/cell
-
Documented progression of disease based on radiographic, clinical or pathologic assessment during or subsequent to the last anticancer regimen received.
-
Breast cancer tumor confirmed to express gpNMB. This will be determined by submitting a tissue sample from the advanced (locally advanced/recurrent or metastatic) disease setting to a central laboratory for analysis.
-
Received no more than two prior chemotherapy treatments for advanced (locally advanced/recurrent or metastatic) breast cancer.
-
Prior chemotherapy treatment must have contained an anthracycline (e.g. doxorubicin or Doxil) if clinically indicated and a taxane (eg: Taxol).
-
ECOG performance status of 0 - 1.
-
Adequate bone marrow, liver and renal function.
Exclusion:
Among other criteria, patients who meet any of the following conditions are NOT eligible for the study:
- Progression/recurrence of breast cancer during or within 3 months of completion of neoadjuvant or adjuvant chemotherapy.
- Ongoing neuropathy or other chemotherapy or radiation-related toxicities that are moderate (Grade 2) or worse in severity.
- Known brain metastases, unless previously treated and asymptomatic for 2 months and not progressive in size or number for 2 months.
- Significant cardiovascular disease.
- Previously received capecitabine and discontinued due to progression or intolerance; previously received CDX-011 or other MMAE containing agents.
- Active systemic infection requiring treatment. Infection controlled by oral therapy will not be exclusionary.
- Chronic use of systemic corticosteroids.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Drug: CDX-011 CDX-011 CDX-011 administered as an intravenous infusion on Day 1 of each 21 day cycle. Capecitabine Capecitabine Capecitabine will be administered on Days 1 through 14 of each 21 day cycle.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) Evaluated every 6 - 9 weeks following treatment initiation PFS is defined as the time from randomization to the earlier of disease progression or death due to any cause. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or progression in a non-target lesion, or the appearance of new lesions. The primary analysis of PFS was based on PFS events determined retrospectively by the central independent review committee, blinded to treatment assignment and investigator assessments according to RECIST 1.1 criteria.
- Secondary Outcome Measures
Name Time Method Pharmacokinetics (PK) Following 1 dose of CDX-011. Concentration of the antibody drug conjugate (ADC), total antibody (TA) and free MMAE will be determined.
Objective Response Rate (ORR) Evaluated every 6 - 9 weeks following treatment initiation ORR is defined as the percentage of patients who achieve best overall response of complete or partial response. The analysis of ORR was based on ORR events determined retrospectively by the central independent review committee, blinded to treatment assignment and investigator assessments according to RECIST 1.1 criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), Complete Response (CR) = Disappearance of all target lesions and non-target lesions, Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions with no progression in non-target lesions and no new lesions.
Overall Survival During treatment and 3 months from end of treatment through end of study or approximately up to 5 years. Overall Survival (OS) is defined as the number of months from randomization to the date of death due to any cause.
Duration of Response Evaluated every 6 - 9 weeks following treatment initiation Duration of response (DOR) is the number of months from the time criteria are first met for either CR or PR, until the first date that PD is objectively documented. The analysis of DOR was determined retrospectively by the central independent review committee,blinded to treatment assignment and investigator assessments according to RECIST 1.1 criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), Complete Response (CR) = Disappearance of all target lesions and non-target lesions, Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions with no progression in non-target lesions and no new lesions.
Adverse Events (AE) Usually following at least 1 cycle of study treatment (1 dose of CDX-011 or capecitabine and until discontinuation of follow-up) The percentage of patients experiencing one or more adverse events will be summarized by treatment arm, relationship to study drug, and severity.
Trial Locations
- Locations (140)
Winship Cancer Institute, Emory University
🇺🇸Atlanta, Georgia, United States
Fondazione Policlinico Universitario A Gemelli
🇮🇹Roma, Lazio, Italy
Hospital Regional Universitario de Malaga - Hospital General
🇪🇸Malaga, Málaga, Spain
University of Chicago
🇺🇸Chicago, Illinois, United States
Cleveland Clinic-Taussig Cancer Institute-R35
🇺🇸Cleveland, Ohio, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Houston Methodist Cancer Center
🇺🇸Houston, Texas, United States
University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Georgia Cancer Specialists Clinic
🇺🇸Atlanta, Georgia, United States
Baptist Cancer Institute
🇺🇸Jacksonville, Florida, United States
ProHEALTH Care Associates
🇺🇸Lake Success, New York, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Hematology and Oncology Specialists
🇺🇸Marrero, Louisiana, United States
Ingalis Memorial Hospital
🇺🇸Harvey, Illinois, United States
Orchard Healthcare Research Inc.
🇺🇸Skokie, Illinois, United States
Peachtree Hematology Oncology Consultants, PC
🇺🇸Atlanta, Georgia, United States
St John's Mercy Medical Center
🇺🇸Saint Louis, Missouri, United States
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
Novant Health
🇺🇸Charlotte, North Carolina, United States
Florida Cancer Specialists
🇺🇸New Port Richey, Florida, United States
Frederick Memorial Hospital
🇺🇸Frederick, Maryland, United States
Signal Point Clinical Research Center, LLC
🇺🇸Middletown, Ohio, United States
Oschner Medical Center
🇺🇸New Orleans, Louisiana, United States
Northwest Georgia Oncology Centers P.C.
🇺🇸Marietta, Georgia, United States
Anne Arundel Medical Center
🇺🇸Annapolis, Maryland, United States
Holy Cross Hospital
🇺🇸Silver Spring, Maryland, United States
Clinical Research Alliance, Inc.
🇺🇸Lake Success, New York, United States
Weill Cornell Medical Center
🇺🇸New York, New York, United States
Tallahassee Memorial HealthCare
🇺🇸Tallahassee, Florida, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Illinois CancerCare
🇺🇸Peoria, Illinois, United States
Macquarie University
🇦🇺Macquarie Park, New South Wales, Australia
Sydney Adventist Hospital
🇦🇺Wahroonga, New South Wales, Australia
Western Hospital
🇦🇺Footscray, Victoria, Australia
Washington University Dept of Oncology
🇺🇸Saint Louis, Missouri, United States
Summit Cancer Care, PC-Savannah
🇺🇸Savannah, Georgia, United States
Oncology Hematology Consultants PA
🇺🇸Fort Worth, Texas, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Guthrie Clinical Research
🇺🇸Sayre, Pennsylvania, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Lafayette General Medical Center
🇺🇸Lafayette, Louisiana, United States
Hunterdon Regional Cancer Center
🇺🇸Flemington, New Jersey, United States
Centre Hospitalier de Mont de Marson - Hôpital Layné
🇫🇷Mont de Marsan, France
Universite de Montreal-Hopital Du Sacre-Coeur De Montreal
🇨🇦Montreal, Quebec, Canada
Oregon Health and Science University
🇺🇸Beaverton, Oregon, United States
Beth Isreal Medical Center
🇺🇸New York, New York, United States
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Grand Hopital de Charleroi asbl
🇧🇪Charleroi, Hainaut, Belgium
Institute Jules Bordet
🇧🇪Bruxelles, Belgium
Centre Antoine Lacassagne Centre Régional de Lutte Contre Le Cancer
🇫🇷Nice, Alpes-Maritimes, France
St. MIchael's Hospital
🇨🇦Toronto, Ontario, Canada
Kliniken der Stadt Koeln gGmbH - Krankenhaus Holweide
🇩🇪Cologne, Germany
GasthuisZusters Antwerpen
🇧🇪Wilrijk, Antwerpen, Belgium
Helios Klinikum Berlin Buch
🇩🇪Berlin, Germany
Centre Jean Bernard Clinique Victor Hugo
🇫🇷Le Mans, Sarthe, France
Institut Sainte Catherine
🇫🇷Avignon, France
St Mary Medical Center
🇺🇸Langhorne, Pennsylvania, United States
Algoma District Cancer Program Sault Area Hospital
🇨🇦Sault Ste Marie, Ontario, Canada
Klinikum Essingen GmbH
🇩🇪Esslingen Am Neckar, Baden-Wurttemberg, Germany
Texas Tech University Health Sciences Center
🇺🇸Lubbock, Texas, United States
The Tweed Hospital
🇦🇺Tweed Heads, New South Wales, Australia
Chattanooga Oncology Hematology Associates
🇺🇸Chattanooga, Tennessee, United States
Clinique Edith Cavell
🇧🇪Brussels Capital Region, Belgium
Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
🇫🇷Lyon, Rhône, France
Centre Oscar Lambret
🇫🇷Lille, France
Martin-Luther-Universität Halle-Wittenberg
🇩🇪Halle, Germany
UZ Leuven
🇧🇪Leuven, Vlaams Brabant, Belgium
Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi
🇮🇹Bologna, Italy
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Asturias, Spain
Universitätsklinikum Münster
🇩🇪Münster, Germany
Consorcio Hospitalario Provincial de Castellon
🇪🇸Castellon de La Plana, Castellón, Spain
Azienda Ospedaliera Fatebenefratelli e Oftaimico
🇮🇹Milano, Lombardia, Italy
Azienda Ospedaliera Citta della Salute e della Scienza de Torino
🇮🇹Torino, Italy
Centre Hospitalier Prive Saint-Gregoire
🇫🇷St Gregoire, France
Klinikum Frankfurt Höchst GmbH
🇩🇪Frankfurt am Main, Germany
Blackpool Victoria Hospital
🇬🇧Blackpool, Lancashire, United Kingdom
Istituto Nazionale Dei Tumori
🇮🇹Milano, Lombardia, Italy
Istituto Europeo Di Oncologia
🇮🇹Milano, Lombardia, Italy
Corporacio Sanitaria Parc Tauli
🇪🇸Sabadell, Barcelona, Spain
Azienda Ospedaliera Universitaria Pisana
🇮🇹Pisa, Toscana, Italy
Sarah Cannon Research Institute UK
🇬🇧City of London, United Kingdom
Universitätsklinikum Erlangen
🇩🇪Erlangen, Germany
Rotkreuzklinikum München
🇩🇪Munich, Germany
Universität Des Saarlandes
🇩🇪Homberg, Germany
Hämatologisch-Onkologische Schwerpunktpraxis
🇩🇪Troisdorf, Germany
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Communidad Delaware, Spain
Centro Di Riferimento Oncologico
🇮🇹Aviano, Pordenone, Italy
Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Royal Sussex County Hospital
🇬🇧Brighton, East Sussex, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, Nottinghamshire, United Kingdom
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
MD Anderson Cancer Center Madrid-Espana
🇪🇸Madrid, Spain
Virginia Piper Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Oncology Hematology Care
🇺🇸Cincinnati, Ohio, United States
Hospices Civils de Lyon
🇫🇷Pierre Benite, France
Barts Health NHS Trust
🇬🇧London, City Of London, United Kingdom
University of California San Francisco
🇺🇸San Francisco, California, United States
Mercy Clinic of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Sarah Cannon Cancer Center
🇺🇸Nashville, Tennessee, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Istituto Clinico Humanitas
🇮🇹Rozzano, Lombardia, Italy
University College London
🇬🇧London, London, City Of, United Kingdom
Sunnybrook Health Sciences Centre Odette Cancer Center
🇨🇦Toronto, Ontario, Canada
Sir Mortimer B Davis Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Universitätsklinikum Düsseldorf
🇩🇪Düsseldorf, Germany
Alabama Oncology
🇺🇸Birmingham, Alabama, United States
University of South Alabama Cancer Research Insititute
🇺🇸Mobile, Alabama, United States
Arizona Cancer Research Alliance
🇺🇸Glendale, Arizona, United States
Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
USC Norris Comprehensive Cancer Center and Hospital
🇺🇸Los Angeles, California, United States
Wellness Hematology Oncology
🇺🇸West Hills, California, United States
University of Miami Miller School of Medicine
🇺🇸Deerfield Beach, Florida, United States
Florida Cancer Specialists South
🇺🇸Fort Myers, Florida, United States
Memorial Regional Hospital
🇺🇸Hollywood, Florida, United States
Center for Biomedical Research, LLC
🇺🇸Knoxville, Tennessee, United States
St. Vincents Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
Townsville Hospital
🇦🇺Douglas, Queensland, Australia
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Joint Ludwig-Austin Dept of Medical Oncology
🇦🇺Heidelberg, Victoria, Australia
Epworth Health Care
🇦🇺Richmond, Victoria, Australia
Institut Curie
🇫🇷Paris, France
Hôpital de La Croix Rousse
🇫🇷Lyon, France
Istituto Scientifico romagnolo Per Lo Studio E La Cura Del Tumori IRST
🇮🇹Meldola, Emilia-Romagna, Italy
Derriford Hospital
🇬🇧Plymouth, Devon, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, Glasgow City, United Kingdom
St. Jude Heritage Medical Group
🇺🇸Fullerton, California, United States
Pacific Cancer Care
🇺🇸Salinas, California, United States
Louisiana State University Health New Orleans
🇺🇸New Orleans, Louisiana, United States
Compassionate Care Research Group
🇺🇸Fountain Valley, California, United States
Kaiser Permaente
🇺🇸Vallejo, California, United States
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
Charleston Hematology Oncology Associates (CHOA)
🇺🇸Charleston, South Carolina, United States
HCA Midwest Health
🇺🇸Kansas City, Missouri, United States