MM-302 Plus Trastuzumab vs. Chemotherapy of Physician's Choice Plus Trastuzumab in HER2-Positive Locally Advanced/Metastatic Breast Cancer Patients

Breast Cancer Clinical Trial

— HERMIONE  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02213744
• Other study ID #: MM-302-02-02-03
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: August 6, 2014
• Last updated: January 4, 2017
• Start date: July 2014
• Est. completion date: June 2017

Study information

• Verified date: January 2017
• Source: Merrimack Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 113
• Est. completion date: June 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• HER2 Positive Breast Cancer

Intervention

Drug:
• MM-302

• Gemcitabine

• Capecitabine

• Vinorelbine

• Trastuzumab

Locations

Country	Name	City	State
Austria	Medizinische Universitat Innsbruck	Innsbruck
Austria	AKh Allgemeines Krankenhaus der Stadt Linz	Linz
Austria	Medical University of Vienna	Wien
Belgium	GZA Ziekenhuizen - Campus Sint-Augustinus	Antwerp
Belgium	University Hospital Antwerp	Antwerp
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Clinique Saint-Joseph	Liege
Canada	University of Alberta- Cross Cancer Institute	Edmonton
Canada	London Regional Cancer Center	London	Ontario
Canada	McGill University Health Center	Quebec
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Czech Republic	Motol University Hospital	Prague
France	Institut de Cancerologie de l'Ouest site Paul Papin	Angers
France	Centre Léon Bérard	Lyon
France	Hopital de l'Institut Curie	Paris
France	Institut de Cancerologie de l'Ouest	Saint-Herblain
France	Institut Claudius Regaud	Toulouse
Germany	Universitatsklinikum des Saarlandes	Homburg
Germany	Universitätsklinikum Schleswig-Holstein	Lubeck
Germany	Interdisziplinares Onkologisches Zentrum	Munich
Italy	Centro Riferimento Oncologico, IRCCS, Istituto Nazionale Tumori	Aviano
Italy	Azienda Ospedaliero-Universitaria di Bologna	Bologna
Italy	Azienda Socio Sanitaria Territoriale di Cremona	Cremina
Italy	Oncology Unit Macerata Hospital	Macerata
Italy	Istituto Europeo di Oncologia	Milan
Italy	Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale	Napoli
Italy	Instituto Oncologico Veneto IRCCS	Padova
Italy	Istituto Clinico Humanitas	Rozzano	Milan
Italy	Azienda Ospedaliero S. Maria di Terni	Terni
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital San Pedro de Alcantara	Cáceres
Spain	Hospital Universitario Reina Sofía	Cordoba
Spain	Hospital Universitario Arnau de Vilanova	Lleida
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	H.U.Son Espases	Palma de Mallorca
Spain	Hospital de Navarra	Pamplona
Spain	Hospital Universitario Virgen de la Macarena	Sevilla
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	New Mexico Cancer Care Alliance	Albuquerque	New Mexico
United States	McFarland Clinic PC	Ames	Iowa
United States	St. Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Texas Oncology- Central Austin Cancer Center	Austin	Texas
United States	Johns Hopkins Medicine- The Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	St. Charles Health System	Bend	Oregon
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Office of Carey K. Anders	Chapel Hill	North Carolina
United States	Tennessee Oncology	Chattanooga	Tennessee
United States	Northwestern University- Robert H. Lurie Comprehensive Cancer Center	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Oncology Hematology Care	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Ohio State University Hospital	Columbus	Ohio
United States	Minnesota Oncology Hematology	Coon Rapids	Minnesota
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Texas Oncology- Medical City	Dallas	Texas
United States	Duke Cancer Institute	Durham	North Carolina
United States	North Shore Hematology Oncology Associates	East Setauket	New York
United States	Texas Oncology	El Paso	Texas
United States	Florida Cancer Specialists & Research Institute	Fort Meyers	Florida
United States	The Center for Cancer and Blood Disorders	Fort Worth	Texas
United States	St. Jude Heritage Healthcare	Fullerton	California
United States	Palo Verde Cancer Center	Glendale	Arizona
United States	Bon Secours Saint Francis Hospital Cancer Center	Greenville	South Carolina
United States	Greenville Health System Cancer Institute	Greenville	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Memorial Regional Hospital	Hollywood	Florida
United States	Texas Oncology-Houston Memorial City	Houston	Texas
United States	The University of Texas- MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Swedish Medical Center	Issaquah	Washington
United States	Mayo Clinic Cancer Center	Jacksonville	Florida
United States	Joliet Oncology-Hematology Associates	Joliet	Illinois
United States	Saint Luke's Hospital	Kansas City	Missouri
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Rocky Mountain Cancer Centers	Littleton	Colorado
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	University of Minnesota- Masonic Cancer Center	Minneapolis	Minnesota
United States	The Sarah Cannon Research Institute	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Smilow Cancer Hospital at Yale New Haven Hospital	New Haven	Connecticut
United States	Sarah Cannon Research Institute	New Port Richey	Florida
United States	Morton Coleman MD	New York	New York
United States	NYU Langone Medical Center	New York	New York
United States	Southeastern Regional Medical Center	Newnan	Georgia
United States	Virginia Oncology Associate	Norfolk	Virginia
United States	UF Health Cancer Center at Orlando Health	Orlando	Florida
United States	Magee-Womens Hospital of UPMC	Pittsburgh	Pennsylvania
United States	Florida Cancer Research Institute	Plantation	Florida
United States	University of Miami Comprehensive Cancer Center	Plantation	Florida
United States	Cancer Care Associates Medical Group	Redondo Beach	California
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Cancer Care Centers of South Texas	San Antonio	Texas
United States	UCSF Medical Center	San Francisco	California
United States	Sansum Clinic	Santa Barbara	California
United States	Mayo Clinic Cancer Center	Scottsdale	Arizona
United States	Barnes-Jewish West County Hospital	St. Louis	Missouri
United States	Northwest Medical Specialties	Tacoma	Washington
United States	University of Arizona Cancer Center	Tucson	Arizona
United States	Texas Oncology	Tyler	Texas
United States	Kaiser Permanent Medical Center	Vallejo	California
United States	Washington Cancer Institute	Washington	District of Columbia
United States	Midwestern Regional Medical Center	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Merrimack Pharmaceuticals

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Czech Republic,  France,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Independently assessed progression-free survival according to modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1		Approximately 2 years	No
Secondary	Locally assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1		Approximately 2 years	No
Secondary	Overall Survival		Approximately 3 years	No
Secondary	Time to Treatment Failure		Approximately 2 years	No
Secondary	Objective Response Rate based on independent and investigator review of tumor assessments		Approximately 2 years	No
Secondary	Duration of Response (DoR) based on independent and investigator review of tumor assessments		Approximately 2 years	No
Secondary	Safety	We will look specifically at the Number of Participants with Adverse Events related to MM-302 as compared to the control arm	Approximately 2 years	Yes
Secondary	Pharmacokinetic exposure of MM-302	Area Under Curve (AUC) Time Frame: Cycles 1 and 2 - pre-infusion, post-infusion, and 168 hours post-dose. An optional timepoint at 8-96 hours post infusion is included during both cycles as well.	Approximately 2 years	No