Clinical trial NCT01997333: Study of Glembatumumab Vedotin (CDX-011) in Patients With Metastatic, gpNMB Over-Expressing, Triple Negative Breast Cancer
Official title: A Randomized Multicenter Pivotal Study of CDX-011 (CR011-vcMMAE)in Patients With Metastatic, gpNMB Over-Expressing, Triple Negative Breast Cancer (The METRIC Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic gpNMB Over-expressing Triple Negative Breast Cancer
Keywords: Metastatic Breast Cancer
Locally advanced breast cancer
Breast cancer
Triple negative
Estrogen
Progesterone
HER2 receptors
Targeted treatment for breast cancer
Antibody-drug-conjugate
Breast Neoplasms
CDX-011
gpNMB
METRIC
Glembatumumab vedotin
Triple Negative Breast Cancer
TNBC
Lead sponsor: Celldex Therapeutics
Sponsor class: INDUSTRY
First posted: 2013-11-28
Enrollment: 327
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

Among other criteria, patients must meet all of the following conditions to be eligible for the study:

1. 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
2. Documented progression of disease based on radiographic, clinical or pathologic assessment during or subsequent to the last anticancer regimen received.
3. 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.
4. Received no more than two prior chemotherapy treatments for advanced (locally advanced/recurrent or metastatic) breast cancer.
5. Prior chemotherapy treatment must have contained an anthracycline (e.g. doxorubicin or Doxil) if clinically indicated and a taxane (eg: Taxol).
6. ECOG performance status of 0 - 1.
7. 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:

1. Progression/recurrence of breast cancer during or within 3 months of completion of neoadjuvant or adjuvant chemotherapy.
2. Ongoing neuropathy or other chemotherapy or radiation-related toxicities that are moderate (Grade 2) or worse in severity.
3. Known brain metastases, unless previously treated and asymptomatic for 2 months and not progressive in size or number for 2 months.
4. Significant cardiovascular disease.
5. Previously received capecitabine and discontinued due to progression or intolerance; previously received CDX-011 or other MMAE containing agents.
6. Active systemic infection requiring treatment. Infection controlled by oral therapy will not be exclusionary.
7. Chronic use of systemic corticosteroids.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Evaluated every 6 - 9 weeks following treatment initiation
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Evaluated every 6 - 9 weeks following treatment initiation
measure: Duration of Response
timeFrame: Evaluated every 6 - 9 weeks following treatment initiation
measure: Overall Survival
timeFrame: During treatment and 3 months from end of treatment through end of study or approximately up to 5 years.
measure: Adverse Events (AE)
timeFrame: Usually following at least 1 cycle of study treatment (1 dose of CDX-011 or capecitabine and until discontinuation of follow-up)
measure: Pharmacokinetics (PK)
timeFrame: Following 1 dose of CDX-011.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Oncology
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Mobile
country: United States
facility: University of South Alabama Cancer Research Insititute
state: Alabama
city: Glendale
country: United States
facility: Arizona Cancer Research Alliance
state: Arizona
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Fountain Valley
country: United States
facility: Compassionate Care Research Group
state: California
city: Fullerton
country: United States
facility: St. Jude Heritage Medical Group
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center and Hospital
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Salinas
country: United States
facility: Pacific Cancer Care
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Vallejo
country: United States
facility: Kaiser Permaente
state: California
city: West Hills
country: United States
facility: Wellness Hematology Oncology
state: California
city: Deerfield Beach
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists South
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital
state: Florida
city: Jacksonville
country: United States
facility: Baptist Cancer Institute
state: Florida
city: New Port Richey
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Memorial HealthCare
state: Florida
city: Atlanta
country: United States
facility: Peachtree Hematology Oncology Consultants, PC
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Atlanta
country: United States
facility: Georgia Cancer Specialists Clinic
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers P.C.
state: Georgia
city: Savannah
country: United States
facility: Summit Cancer Care, PC-Savannah
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Harvey
country: United States
facility: Ingalis Memorial Hospital
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare
state: Illinois
city: Skokie
country: United States
facility: Orchard Healthcare Research Inc.
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Lafayette
country: United States
facility: Lafayette General Medical Center
state: Louisiana
city: Marrero
country: United States
facility: Hematology and Oncology Specialists
state: Louisiana
city: New Orleans
country: United States
facility: Louisiana State University Health New Orleans
state: Louisiana
city: New Orleans
country: United States
facility: Oschner Medical Center
state: Louisiana
city: Annapolis
country: United States
facility: Anne Arundel Medical Center
state: Maryland
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Frederick
country: United States
facility: Frederick Memorial Hospital
state: Maryland
city: Silver Spring
country: United States
facility: Holy Cross Hospital
state: Maryland
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Center
state: Minnesota
city: Kansas City
country: United States
facility: HCA Midwest Health
state: Missouri
city: Saint Louis
country: United States
facility: Washington University Dept of Oncology
state: Missouri
city: Saint Louis
country: United States
facility: St John's Mercy Medical Center
state: Missouri
city: Flemington
country: United States
facility: Hunterdon Regional Cancer Center
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Lake Success
country: United States
facility: Clinical Research Alliance, Inc.
state: New York
city: Lake Success
country: United States
facility: ProHEALTH Care Associates
state: New York
city: New York
country: United States
facility: Beth Isreal Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Charlotte
country: United States
facility: Novant Health
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic-Taussig Cancer Institute-R35
state: Ohio
city: Middletown
country: United States
facility: Signal Point Clinical Research Center, LLC
state: Ohio
city: Oklahoma City
country: United States
facility: Mercy Clinic of Oklahoma
state: Oklahoma
city: Beaverton
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Langhorne
country: United States
facility: St Mary Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Sayre
country: United States
facility: Guthrie Clinical Research
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Hematology Oncology Associates (CHOA)
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Oncology Hematology Associates
state: Tennessee
city: Knoxville
country: United States
facility: Center for Biomedical Research, LLC
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center
state: Tennessee
city: Fort Worth
country: United States
facility: Oncology Hematology Consultants PA
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Houston Methodist Cancer Center
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Darlinghurst
country: Australia
facility: St. Vincents Hospital Sydney
state: New South Wales
city: Macquarie Park
country: Australia
facility: Macquarie University
state: New South Wales
city: Tweed Heads
country: Australia
facility: The Tweed Hospital
state: New South Wales
city: Wahroonga
country: Australia
facility: Sydney Adventist Hospital
state: New South Wales
city: Douglas
country: Australia
facility: Townsville Hospital
state: Queensland
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Footscray
country: Australia
facility: Western Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: Joint Ludwig-Austin Dept of Medical Oncology
state: Victoria
city: Richmond
country: Australia
facility: Epworth Health Care
state: Victoria
city: Wilrijk
country: Belgium
facility: GasthuisZusters Antwerpen
state: Antwerpen
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi asbl
state: Hainaut
city: Leuven
country: Belgium
facility: UZ Leuven
state: Vlaams Brabant
city: Brussels Capital Region
country: Belgium
facility: Clinique Edith Cavell
city: Bruxelles
country: Belgium
facility: Institute Jules Bordet
city: Sault Ste Marie
country: Canada
facility: Algoma District Cancer Program Sault Area Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre Odette Cancer Center
state: Ontario
city: Toronto
country: Canada
facility: St. MIchael's Hospital
state: Ontario
city: Montreal
country: Canada
facility: Sir Mortimer B Davis Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: Universite de Montreal-Hopital Du Sacre-Coeur De Montreal
state: Quebec
city: Nice
country: France
facility: Centre Antoine Lacassagne Centre Régional de Lutte Contre Le Cancer
state: Alpes-Maritimes
city: Lyon
country: France
facility: Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
state: Rhône
city: Le Mans
country: France
facility: Centre Jean Bernard Clinique Victor Hugo
state: Sarthe
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Hôpital de La Croix Rousse
city: Mont de Marsan
country: France
facility: Centre Hospitalier de Mont de Marson - Hôpital Layné
city: Paris
country: France
facility: Institut Curie
city: Pierre Benite
country: France
facility: Hospices Civils de Lyon
city: St Gregoire
country: France
facility: Centre Hospitalier Prive Saint-Gregoire
city: Esslingen Am Neckar
country: Germany
facility: Klinikum Essingen GmbH
state: Baden-Wurttemberg
city: Berlin
country: Germany
facility: Helios Klinikum Berlin Buch
city: Cologne
country: Germany
facility: Kliniken der Stadt Koeln gGmbH - Krankenhaus Holweide
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Frankfurt am Main
country: Germany
facility: Klinikum Frankfurt Höchst GmbH
city: Halle
country: Germany
facility: Martin-Luther-Universität Halle-Wittenberg
city: Homberg
country: Germany
facility: Universität Des Saarlandes
city: Munich
country: Germany
facility: Rotkreuzklinikum München
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Troisdorf
country: Germany
facility: Hämatologisch-Onkologische Schwerpunktpraxis
city: Meldola
country: Italy
facility: Istituto Scientifico romagnolo Per Lo Studio E La Cura Del Tumori IRST
state: Emilia-Romagna
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli
state: Lazio
city: Milano
country: Italy
facility: Azienda Ospedaliera Fatebenefratelli e Oftaimico
state: Lombardia
city: Milano
country: Italy
facility: Istituto Nazionale Dei Tumori
state: Lombardia
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
state: Lombardia
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Lombardia
city: Aviano
country: Italy
facility: Centro Di Riferimento Oncologico
state: Pordenone
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana
state: Toscana
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi
city: Torino
country: Italy
facility: Azienda Ospedaliera Citta della Salute e della Scienza de Torino
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli
state: Barcelona
city: Castellon de La Plana
country: Spain
facility: Consorcio Hospitalario Provincial de Castellon
state: Castellón
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
state: Communidad Delaware
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga - Hospital General
state: Málaga
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: MD Anderson Cancer Center Madrid-Espana
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: London
country: United Kingdom
facility: Barts Health NHS Trust
state: City Of London
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: Devon
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital
state: East Sussex
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Glasgow City
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospital
state: Lancashire
city: London
country: United Kingdom
facility: University College London
state: London, City Of
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
state: Nottinghamshire
city: City of London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
Study officials:
References: