Metastatic gpNMB Over-expressing Triple Negative Breast Cancer Clinical Trial
— METRICOfficial 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)
| Verified date | March 2019 |
| Source | Celldex Therapeutics |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 327 |
| Est. completion date | August 7, 2018 |
| Est. primary completion date | November 30, 2017 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
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. |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Box Hill Hospital | Box Hill | Victoria |
| Australia | St. Vincents Hospital Sydney | Darlinghurst | New South Wales |
| Australia | Townsville Hospital | Douglas | Queensland |
| Australia | Western Hospital | Footscray | Victoria |
| Australia | Joint Ludwig-Austin Dept of Medical Oncology | Heidelberg | Victoria |
| Australia | Macquarie University | Macquarie Park | New South Wales |
| Australia | Epworth Health Care | Richmond | Victoria |
| Australia | The Tweed Hospital | Tweed Heads | New South Wales |
| Australia | Sydney Adventist Hospital | Wahroonga | New South Wales |
| Belgium | Clinique Edith Cavell | Brussels Capital Region | |
| Belgium | Institute Jules Bordet | Bruxelles | |
| Belgium | Grand Hopital de Charleroi asbl | Charleroi | Hainaut |
| Belgium | UZ Leuven | Leuven | Vlaams Brabant |
| Belgium | GasthuisZusters Antwerpen | Wilrijk | Antwerpen |
| Canada | Sir Mortimer B Davis Jewish General Hospital | Montreal | Quebec |
| Canada | Universite de Montreal-Hopital Du Sacre-Coeur De Montreal | Montreal | Quebec |
| Canada | Algoma District Cancer Program Sault Area Hospital | Sault Ste Marie | Ontario |
| Canada | St. MIchael's Hospital | Toronto | Ontario |
| Canada | Sunnybrook Health Sciences Centre Odette Cancer Center | Toronto | Ontario |
| France | Institut Sainte Catherine | Avignon | |
| France | Centre Jean Bernard Clinique Victor Hugo | Le Mans | Sarthe |
| France | Centre Oscar Lambret | Lille | |
| France | Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes | Lyon | Rhône |
| France | Hôpital de La Croix Rousse | Lyon | |
| France | Centre Hospitalier de Mont de Marson - Hôpital Layné | Mont de Marsan | |
| France | Centre Antoine Lacassagne Centre Régional de Lutte Contre Le Cancer | Nice | Alpes-Maritimes |
| France | Institut Curie | Paris | |
| France | Hospices Civils de Lyon | Pierre Benite | |
| France | Centre Hospitalier Prive Saint-Gregoire | St Gregoire | |
| Germany | Helios Klinikum Berlin Buch | Berlin | |
| Germany | Kliniken der Stadt Koeln gGmbH - Krankenhaus Holweide | Cologne | |
| Germany | Universitätsklinikum Düsseldorf | Düsseldorf | |
| Germany | Universitätsklinikum Erlangen | Erlangen | |
| Germany | Klinikum Essingen GmbH | Esslingen Am Neckar | Baden-Wurttemberg |
| Germany | Klinikum Frankfurt Höchst GmbH | Frankfurt am Main | |
| Germany | Martin-Luther-Universität Halle-Wittenberg | Halle | |
| Germany | Universität Des Saarlandes | Homberg | |
| Germany | Rotkreuzklinikum München | Munich | |
| Germany | Universitätsklinikum Münster | Münster | |
| Germany | Hämatologisch-Onkologische Schwerpunktpraxis | Troisdorf | |
| Italy | Centro Di Riferimento Oncologico | Aviano | Pordenone |
| Italy | Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi | Bologna | |
| Italy | Istituto Scientifico romagnolo Per Lo Studio E La Cura Del Tumori IRST | Meldola | Emilia-Romagna |
| Italy | Azienda Ospedaliera Fatebenefratelli e Oftaimico | Milano | Lombardia |
| Italy | Istituto Europeo Di Oncologia | Milano | Lombardia |
| Italy | Istituto Nazionale Dei Tumori | Milano | Lombardia |
| Italy | Azienda Ospedaliera Universitaria Pisana | Pisa | Toscana |
| Italy | Fondazione Policlinico Universitario A Gemelli | Roma | Lazio |
| Italy | Istituto Clinico Humanitas | Rozzano | Lombardia |
| Italy | Azienda Ospedaliera Citta della Salute e della Scienza de Torino | Torino | |
| Spain | Hospital Universitari Germans Trias i Pujol | Badalona | Barcelona |
| Spain | Hospital Clinic de Barcelona | Barcelona | |
| Spain | Hospital Universitario Vall d'Hebron | Barcelona | |
| Spain | Consorcio Hospitalario Provincial de Castellon | Castellon de La Plana | Castellón |
| Spain | Hospital Clinico San Carlos | Madrid | |
| Spain | Hospital Universitario Ramon y Cajal | Madrid | Communidad Delaware |
| Spain | MD Anderson Cancer Center Madrid-Espana | Madrid | |
| Spain | Hospital Regional Universitario de Malaga - Hospital General | Malaga | Málaga |
| Spain | Hospital Universitario Central de Asturias | Oviedo | Asturias |
| Spain | Corporacio Sanitaria Parc Tauli | Sabadell | Barcelona |
| Spain | Hospital Clinico Universitario de Valencia | Valencia | |
| United Kingdom | Blackpool Victoria Hospital | Blackpool | Lancashire |
| United Kingdom | Royal Sussex County Hospital | Brighton | East Sussex |
| United Kingdom | Sarah Cannon Research Institute UK | City of London | |
| United Kingdom | Beatson West of Scotland Cancer Centre | Glasgow | Glasgow City |
| United Kingdom | Barts Health NHS Trust | London | City Of London |
| United Kingdom | University College London | London | London, City Of |
| United Kingdom | Nottingham University Hospitals NHS Trust | Nottingham | Nottinghamshire |
| United Kingdom | Derriford Hospital | Plymouth | Devon |
| United States | Anne Arundel Medical Center | Annapolis | Maryland |
| United States | Georgia Cancer Specialists Clinic | Atlanta | Georgia |
| United States | Peachtree Hematology Oncology Consultants, PC | Atlanta | Georgia |
| United States | Winship Cancer Institute, Emory University | Atlanta | Georgia |
| United States | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland |
| United States | University of Maryland | Baltimore | Maryland |
| United States | Oregon Health and Science University | Beaverton | Oregon |
| United States | Alabama Oncology | Birmingham | Alabama |
| United States | University of Alabama at Birmingham | Birmingham | Alabama |
| United States | Charleston Hematology Oncology Associates (CHOA) | Charleston | South Carolina |
| United States | Novant Health | Charlotte | North Carolina |
| United States | Chattanooga Oncology Hematology Associates | Chattanooga | Tennessee |
| United States | University of Chicago | Chicago | Illinois |
| United States | Oncology Hematology Care | Cincinnati | Ohio |
| United States | Cleveland Clinic-Taussig Cancer Institute-R35 | Cleveland | Ohio |
| United States | University of Miami Miller School of Medicine | Deerfield Beach | Florida |
| United States | Duke University Medical Center | Durham | North Carolina |
| United States | Hunterdon Regional Cancer Center | Flemington | New Jersey |
| United States | Florida Cancer Specialists South | Fort Myers | Florida |
| United States | Oncology Hematology Consultants PA | Fort Worth | Texas |
| United States | Compassionate Care Research Group | Fountain Valley | California |
| United States | Frederick Memorial Hospital | Frederick | Maryland |
| United States | St. Jude Heritage Medical Group | Fullerton | California |
| United States | Arizona Cancer Research Alliance | Glendale | Arizona |
| United States | Hackensack University Medical Center | Hackensack | New Jersey |
| United States | Ingalis Memorial Hospital | Harvey | Illinois |
| United States | Memorial Regional Hospital | Hollywood | Florida |
| 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 | Baptist Cancer Institute | Jacksonville | Florida |
| United States | HCA Midwest Health | Kansas City | Missouri |
| United States | Center for Biomedical Research, LLC | Knoxville | Tennessee |
| United States | Lafayette General Medical Center | Lafayette | Louisiana |
| United States | Clinical Research Alliance, Inc. | Lake Success | New York |
| United States | ProHEALTH Care Associates | Lake Success | New York |
| United States | St Mary Medical Center | Langhorne | Pennsylvania |
| 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 | Texas Tech University Health Sciences Center | Lubbock | Texas |
| United States | Northwest Georgia Oncology Centers P.C. | Marietta | Georgia |
| United States | Hematology and Oncology Specialists | Marrero | Louisiana |
| United States | Signal Point Clinical Research Center, LLC | Middletown | Ohio |
| United States | Virginia Piper Cancer Center | Minneapolis | Minnesota |
| United States | University of South Alabama Cancer Research Insititute | Mobile | Alabama |
| United States | Sarah Cannon Cancer Center | Nashville | Tennessee |
| United States | Louisiana State University Health New Orleans | New Orleans | Louisiana |
| United States | Oschner Medical Center | New Orleans | Louisiana |
| United States | Florida Cancer Specialists | New Port Richey | Florida |
| United States | Beth Isreal Medical Center | New York | New York |
| United States | Weill Cornell Medical Center | New York | New York |
| United States | Mercy Clinic of Oklahoma | Oklahoma City | Oklahoma |
| United States | Illinois CancerCare | Peoria | Illinois |
| United States | Fox Chase Cancer Center | Philadelphia | Pennsylvania |
| United States | University of California Davis Medical Center | Sacramento | California |
| United States | St John's Mercy Medical Center | Saint Louis | Missouri |
| United States | Washington University Dept of Oncology | Saint Louis | Missouri |
| United States | Pacific Cancer Care | Salinas | California |
| United States | University of California San Francisco | San Francisco | California |
| United States | Summit Cancer Care, PC-Savannah | Savannah | Georgia |
| United States | Guthrie Clinical Research | Sayre | Pennsylvania |
| United States | Seattle Cancer Care Alliance | Seattle | Washington |
| United States | Swedish Cancer Institute | Seattle | Washington |
| United States | Holy Cross Hospital | Silver Spring | Maryland |
| United States | Orchard Healthcare Research Inc. | Skokie | Illinois |
| United States | Stony Brook University Medical Center | Stony Brook | New York |
| United States | Tallahassee Memorial HealthCare | Tallahassee | Florida |
| United States | Arizona Cancer Center | Tucson | Arizona |
| United States | Carle Cancer Center | Urbana | Illinois |
| United States | Kaiser Permaente | Vallejo | California |
| United States | Wellness Hematology Oncology | West Hills | California |
| Lead Sponsor | Collaborator |
|---|---|
| Celldex Therapeutics |
United States, Australia, Belgium, Canada, France, Germany, Italy, Spain, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Progression Free Survival (PFS) | 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. | Evaluated every 6 - 9 weeks following treatment initiation | |
| Secondary | Objective Response Rate (ORR) | 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. | Evaluated every 6 - 9 weeks following treatment initiation | |
| Secondary | Duration of Response | 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. | Evaluated every 6 - 9 weeks following treatment initiation | |
| Secondary | Overall Survival | Overall Survival (OS) is defined as the number of months from randomization to the date of death due to any cause. | During treatment and 3 months from end of treatment through end of study or approximately up to 5 years. | |
| Secondary | Adverse Events (AE) | The percentage of patients experiencing one or more adverse events will be summarized by treatment arm, relationship to study drug, and severity. | Usually following at least 1 cycle of study treatment (1 dose of CDX-011 or capecitabine and until discontinuation of follow-up) | |
| Secondary | Pharmacokinetics (PK) | Concentration of the antibody drug conjugate (ADC), total antibody (TA) and free MMAE will be determined. | Following 1 dose of CDX-011. |