Clinical trial NCT02213744: MM-302 Plus Trastuzumab vs. Chemotherapy of Physician's Choice Plus Trastuzumab in HER2-Positive Locally Advanced/Metastatic Breast Cancer Patients
Official title: A Randomized, Multicenter, Open Label Study of MM-302 Plus Trastuzumab vs. Chemotherapy of Physician's Choice Plus Trastuzumab in Anthracycline Naive Patients With Locally Advanced/Metastatic HER2-Positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Breast Cancer
HER2 Positive Breast Cancer
Keywords: HER2-positive
HER2+
HER2
Locally Advanced Breast Cancer
Metastatic Breast Cancer
trastuzumab
Herceptin
pertuzumab
ado-trastuzumab emtansine
TDM-1
Perjeta
Kadcyla
Lead sponsor: Merrimack Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2014-08-11
Enrollment: 113
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: This study is an open label, randomized, multicenter trial of MM-302 plus trastuzumab. The trial is designed to demonstrate whether MM-302 plus trastuzumab is more effective than the chemotherapy of physician's choice (CPC) plus trastuzumab in locally advanced/metastatic HER2-positive breast cancer patients. Patients may not have been previously treated with an anthracycline in any setting. Patients must have received prior treatment with trastuzumab in any setting, have either progressed or are intolerant to ado-trastuzumab emtansine in the metastatic or locally advanced setting, have either progressed or are intolerant to pertuzumab in the metastatic or locally advanced setting or had disease recurrence within 12 months of pertuzumab treatment in the neoadjuvant or adjuvant setting.


Eligibility criteria: Inclusion Criteria:

* Patients must have histologically or cytologically confirmed invasive cancer of the breast
* Patients must have documented locally advanced/metastatic disease, defined by the investigator, which is not amenable to resection with curative intent.
* Patients must have HER2-positive breast cancer as defined by ASCO/CAP 2013 guidelines that is confirmed by a Sponsor-designated central laboratory
* Patients must have progressed on, or be intolerant to pertuzumab in the LABC/MBC setting or had disease recurrence within 12 months of pertuzumab treatment in the neoadjuvant or adjuvant setting.
* Patients must have progressed on, or be intolerant to ado-trastuzumab emtansine in the LABC/MBC setting
* Patients must have been previously treated with trastuzumab in any setting (which may have been previously administered with or without pertuzumab)
* ECOG Performance Status of 0 or 1

Exclusion Criteria:

* Patients who have previously been treated with doxorubicin, liposomal doxorubicin, epirubicin, mitoxantrone, or any other anthracycline derivative
* Subjects with central nervous system (CNS) metastases, unless they have been treated and are stable without symptoms for 4 weeks after completion of treatment and must be off steroids for at least 4 weeks prior to enrollment
* Patients with any class of New York Heart Association (NYHA) CHF or heart failure with preserved ejection fraction (HFPEF)
* Patients with a history of known coronary artery disease or a myocardial infarction within the last 12 months
* Patients with a known history of serious cardiac arrhythmias requiring treatment (exception: controlled atrial fibrillation, paroxysmal supraventricular tachycardia)
* Patients who previously discontinued trastuzumab due to unacceptable cardiac toxicity
* Patients with a history of LVEF decline to below 50% during or after prior trastuzumab/lapatinib or other HER2 directed therapy.

Primary outcomes:
measure: Independently assessed progression-free survival according to modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
timeFrame: Approximately 2 years
Secondary outcomes:
measure: Locally assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
timeFrame: Approximately 2 years
measure: Overall Survival
timeFrame: Approximately 3 years
measure: Time to Treatment Failure
timeFrame: Approximately 2 years
measure: Objective Response Rate based on independent and investigator review of tumor assessments
timeFrame: Approximately 2 years
measure: Duration of Response (DoR) based on independent and investigator review of tumor assessments
timeFrame: Approximately 2 years
measure: Safety
timeFrame: Approximately 2 years
measure: Pharmacokinetic exposure of MM-302
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Palo Verde Cancer Center
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Cancer Center
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Fullerton
country: United States
facility: St. Jude Heritage Healthcare
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Redondo Beach
country: United States
facility: Cancer Care Associates Medical Group
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Santa Barbara
country: United States
facility: Sansum Clinic
state: California
city: Vallejo
country: United States
facility: Kaiser Permanent Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Littleton
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale New Haven Hospital
state: Connecticut
city: Washington
country: United States
facility: Washington Cancer Institute
state: District of Columbia
city: Fort Meyers
country: United States
facility: Florida Cancer Specialists & Research Institute
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Cancer Center
state: Florida
city: New Port Richey
country: United States
facility: Sarah Cannon Research Institute
state: Florida
city: Orlando
country: United States
facility: UF Health Cancer Center at Orlando Health
state: Florida
city: Plantation
country: United States
facility: Florida Cancer Research Institute
state: Florida
city: Plantation
country: United States
facility: University of Miami Comprehensive Cancer Center
state: Florida
city: Newnan
country: United States
facility: Southeastern Regional Medical Center
state: Georgia
city: Chicago
country: United States
facility: Northwestern University- Robert H. Lurie Comprehensive Cancer Center
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates
state: Illinois
city: Zion
country: United States
facility: Midwestern Regional Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic PC
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins Medicine- The Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Coon Rapids
country: United States
facility: Minnesota Oncology Hematology
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota- Masonic Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Hospital
state: Missouri
city: St. Louis
country: United States
facility: Barnes-Jewish West County Hospital
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance
state: New Mexico
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: East Setauket
country: United States
facility: North Shore Hematology Oncology Associates
state: New York
city: New York
country: United States
facility: Morton Coleman MD
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: Chapel Hill
country: United States
facility: Office of Carey K. Anders
state: North Carolina
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Hospital
state: Ohio
city: Bend
country: United States
facility: St. Charles Health System
state: Oregon
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital of UPMC
state: Pennsylvania
city: Greenville
country: United States
facility: Bon Secours Saint Francis Hospital Cancer Center
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute
state: South Carolina
city: Chattanooga
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology- Central Austin Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology- Medical City
state: Texas
city: El Paso
country: United States
facility: Texas Oncology
state: Texas
city: Fort Worth
country: United States
facility: The Center for Cancer and Blood Disorders
state: Texas
city: Houston
country: United States
facility: Texas Oncology-Houston Memorial City
state: Texas
city: Houston
country: United States
facility: The University of Texas- MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas
state: Texas
city: Tyler
country: United States
facility: Texas Oncology
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Norfolk
country: United States
facility: Virginia Oncology Associate
state: Virginia
city: Issaquah
country: United States
facility: Swedish Medical Center
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Innsbruck
country: Austria
facility: Medizinische Universitat Innsbruck
city: Linz
country: Austria
facility: AKh Allgemeines Krankenhaus der Stadt Linz
city: Wien
country: Austria
facility: Medical University of Vienna
city: Antwerp
country: Belgium
facility: GZA Ziekenhuizen - Campus Sint-Augustinus
city: Antwerp
country: Belgium
facility: University Hospital Antwerp
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Liege
country: Belgium
facility: Clinique Saint-Joseph
city: London
country: Canada
facility: London Regional Cancer Center
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Edmonton
country: Canada
facility: University of Alberta- Cross Cancer Institute
city: Quebec
country: Canada
facility: McGill University Health Center
city: Prague
country: Czech Republic
facility: Motol University Hospital
city: Angers
country: France
facility: Institut de Cancerologie de l'Ouest site Paul Papin
city: Lyon
country: France
facility: Centre Léon Bérard
city: Paris
country: France
facility: Hopital de l'Institut Curie
city: Saint-Herblain
country: France
facility: Institut de Cancerologie de l'Ouest
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Homburg
country: Germany
facility: Universitatsklinikum des Saarlandes
city: Lubeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Munich
country: Germany
facility: Interdisziplinares Onkologisches Zentrum
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milan
city: Aviano
country: Italy
facility: Centro Riferimento Oncologico, IRCCS, Istituto Nazionale Tumori
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna
city: Cremina
country: Italy
facility: Azienda Socio Sanitaria Territoriale di Cremona
city: Macerata
country: Italy
facility: Oncology Unit Macerata Hospital
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale
city: Padova
country: Italy
facility: Instituto Oncologico Veneto IRCCS
city: Terni
country: Italy
facility: Azienda Ospedaliero S. Maria di Terni
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Lleida
country: Spain
facility: Hospital Universitario Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Palma de Mallorca
country: Spain
facility: H.U.Son Espases
city: Pamplona
country: Spain
facility: Hospital de Navarra
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de la Macarena
Study officials:
References:
citation: Miller K, Cortes J, Hurvitz SA, Krop IE, Tripathy D, Verma S, Riahi K, Reynolds JG, Wickham TJ, Molnar I, Yardley DA. HERMIONE: a randomized Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician's choice plus trastuzumab in patients with previously treated, anthracycline-naive, HER2-positive, locally advanced/metastatic breast cancer. BMC Cancer. 2016 Jun 3;16:352. doi: 10.1186/s12885-016-2385-z.