Fulvestrant With or Without Lapatinib in Treating Postmenopausal Women With Stage III or Stage IV Breast Cancer That is Hormone Receptor-Positive

Recurrent Breast Carcinoma Clinical Trial

Official title:

Endocrine Therapy With or Without Inhibition of EGF and HER2 Growth Factor Receptors: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Fulvestrant With or Without Lapatinib (GW572016) for Postmenopausal Women With Hormone Receptor Positive Advanced Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00390455
• Other study ID #: NCI-2009-00475
• Secondary ID: NCI-2009-00475CD
• Status: Completed
• Phase: Phase 3
• Start date: September 15, 2006
• Est. completion date: July 2, 2014

Study information

• Verified date: November 2019
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase III trial studies fulvestrant and lapatinib to see how well they work compared to fulvestrant and a placebo in treating postmenopausal women with stage III or stage IV breast cancer that is hormone receptor-positive. Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by lowering the amount of estrogen the body makes. Lapatinib may stop the growth of breast cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether fulvestrant is more effective with or without lapatinib in treating breast cancer.

Description:

PRIMARY OBJECTIVES:

I. To compare the effect, in terms of progression free survival, of the antiestrogen fulvestrant alone with fulvestrant administered in combination with the dual-kinase inhibitor lapatinib for postmenopausal women with estrogen receptor (ER) and/or progesterone receptor (PgR) positive advanced breast cancer.

SECONDARY OBJECTIVES:

I. To compare the effects of fulvestrant alone with fulvestrant and lapatinib on other clinical endpoints, including response rate, response and stable disease rate (complete response [CR] + partial response [PR] + stable disease >= 6 months), duration of response, overall survival, symptom checklist scores, and toxicity.

II. To define predictive markers of clinical activity among women receiving fulvestrant with or without lapatinib.

III. To determine if the clinical benefits for combination of hormonal and growth factor inhibitor therapy are most pronounced in women whose tumors express higher levels of ER, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), phosphorylated protein kinase B (pAkt), and/or phosphorylated mitogen-activated protein kinase 1/2 (pERK1/2).

IV. To serologically determine if HER2 extracellular domain (ECD) and EGFR ECD levels can identify patients with a greater likelihood of response and clinical benefit to fulvestrant with or without lapatinib.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive lapatinib ditosylate orally (PO) once daily (QD) on days 1-28 and fulvestrant intramuscularly (IM) on days 1 and 15 of course 1 and on day 1 of each subsequent course.

ARM II: Patients receive placebo PO QD on days 1-28 and fulvestrant as in Arm I.

In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 2 years and then annually for 3 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 295
• Est. completion date: July 2, 2014
• Est. primary completion date: July 1, 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologic, pathologic or cytologic diagnosis of cancer of the female breast in either primary or metastatic setting; histological documentation of metastatic/recurrent disease is not required if there is unequivocal clinical evidence for recurrence

• Stage IV breast cancer (using American Joint Committee on Cancer [AJCC] criteria, 6th edition), or locally advanced (stage III) breast cancer not considered amenable to curative therapy

• Patients with symptomatic brain metastases or other symptomatic central nervous system (CNS) metastases are not eligible for the study; no screening studies are required among asymptomatic patients; patients with previously treated brain metastases, who are free of symptoms referable to CNS disease and who are > 3 months from treatment for brain metastases are eligible

• Tumors (as determined on pathology from either primary or metastatic sites) must be potentially sensitive to endocrine therapy, defined as expressing estrogen receptor (ER) and/or progesterone receptor (PgR) as determined immunohistochemical methods according to the local institution's standard protocol, >= 1% cells will be considered to be positive

• The protocol has been amended to permit tumors with any HER2 status, though a determination of HER2 status must have been made; patients will be considered to be eligible if HER2 expression is documented by one of the following methods:

• Immunohistochemistry (IHC) 0 (i.e., negative), 1+, 2+, or 3+ levels of expression, or

• Gene amplification (fluorescent in situ hybridization [FISH]) positive or negative

• Patients must have at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 2.0 cm with conventional techniques or as >= 1.0 cm with spiral computed tomography (CT) scan

• Exception: Patients with lytic or blastic bone metastases as their only site of disease will be eligible for the study even though these patients are not considered to have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria; these patients will be evaluable for time to progression, but not response

• Patients with all other lesions, including small lesions (longest diameter < 2.0 cm with conventional techniques or < 1.0 cm with spiral CT scan) and truly non-measurable lesions including those listed below are not eligible

• Lesions that are considered non-measurable include the following:

• Bone lesions (women with bone lesions will be eligible as described above)

• Leptomeningeal disease

• Ascites

• Pleural/pericardial effusion

• Inflammatory breast cancer

• Lymphangitis cutis/pulmonitis

• Abdominal masses that are not confirmed and followed by imaging techniques

• Cystic lesions

• Patients must have had one or two prior endocrine treatments for breast cancer in either the adjuvant or metastatic setting, exclusive of treatment-related amenorrhea or ovarian suppression; sequential use of two different third-generation aromatase inhibitors is considered "one" treatment; it is not required that tumors be resistant to such treatments; for example:

• A patient with de novo metastatic breast cancer who had never received endocrine therapy is not eligible;

• A patient who received adjuvant tamoxifen and subsequent therapy with an aromatase inhibitor (adjuvant or metastatic) is eligible;

• A patient who received an aromatase inhibitor in either the adjuvant or metastatic setting, and who discontinued therapy after several months because of side effects, is eligible;

• A patient who received an aromatase inhibitor in the adjuvant setting is eligible, regardless of whether they did or did not receive tamoxifen at some point;

• A patient who received adjuvant tamoxifen, and subsequently a nonsteroidal aromatase inhibitor and a steroidal aromatase inhibitor for advanced breast cancer in the adjuvant or metastatic setting is eligible;

• A patient who received adjuvant tamoxifen, and then a nonsteroidal aromatase inhibitor and subsequently megesterol acetate for advanced breast cancer is not eligible

• Tumors potentially sensitive to endocrine therapy, defined as >= 3 months of prior endocrine therapy without disease progression in the adjuvant or metastatic setting

• Patients must have had prior treatment in either the adjuvant or metastatic setting with a commercially available third-generation aromatase inhibitor (i.e. anastrozole, exemestane, or letrozole); it is not required that tumors be resistant to such therapies

• Patients may have received up to one prior chemotherapy regimen for stage IV breast cancer; prior chemotherapy in the adjuvant and/or neoadjuvant setting is permitted; patients must have finished chemotherapy at least 1 week prior to starting protocol based treatment

• Patients may have received prior trastuzumab therapy for stage IV breast cancer, in combination with up to one chemotherapy and/or endocrine therapy regimen, but that must have concluded at least 3 weeks prior to starting protocol-based therapy; prior trastuzumab therapy in the adjuvant and/or neoadjuvant setting is permitted, but must have concluded at least 3 weeks prior to starting protocol-based therapy

• Prior therapy with commercially available inhibitor of EGFR (including but not limited to gefitinib, erlotinib, lapatinib or cetuximab) or experimental inhibitors of EGFR is prohibited

• Patients may have initiated bisphosphonate therapy prior to study entry; such patients will have bone lesions considered evaluable for progression but not for response

• Prior fulvestrant therapy is prohibited

• Patients receiving a gonadotropin-releasing hormone (GnRH) agonist for ovarian suppression must remain on such therapy throughout the course of protocol treatment; patients must discontinue other endocrine treatments, including systemic hormone-replacement therapy and intravaginal estrogens prior to study entry; patients must have concluded radiation therapy prior to study entry; patients must be at least 1 week from prior chemotherapy or 3 weeks from prior trastuzumab therapy, with adequate recovery of bone marrow function and performance status

• Patients must be postmenopausal women, defined as a woman fulfilling any of the following criteria:

• Age >= 60 years; or

• Age >= 45 years with an intact uterus and amenorrhea for 12 months or more; or

• History of bilateral oophorectomy; or

• Follicle stimulating hormone (FSH) levels within postmenopausal range according to the ranges established by the testing facility; or

• Treatment with a GnRH agonist for ovarian suppression for at least 3 consecutive months prior to study registration, and remaining on such therapy throughout the course of protocol treatment

• Women who are pregnant or nursing are not eligible for the study; clinicians should advise patients that there are no data for the safety of lapatinib or fulvestrant among pregnant patients, nor data on the impact of these agents on fertility or pregnancy

• Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-2

• Absence of pending visceral crisis, in the opinion of the treating physician

• Absence of acquired or inherited bleeding disorder

• Absence of need for therapeutic systemic anticoagulation (defined as maintaining international normalized ratio [INR] > 1.6); patients may take low-dose warfarin or aspirin (or equivalent) for maintenance of central venous catheter patency

• Granulocytes >= 1,000/µl

• Platelet count >= 100,000/µl

• Creatinine =< 2 mg/dl

• Total bilirubin =< 1.5 x upper limits of normal (ULN) unless due to Gilbert's syndrome

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN without liver metastases; =< 5 x ULN with liver metastases

• INR =< 1.6

• Left ventricular ejection fraction (LVEF) within institutional limits of normal

Related Conditions & MeSH terms

• Breast Neoplasms
• Carcinoma
• Estrogen Receptor Positive
• HER2 Positive Breast Carcinoma
• HER2/Neu Negative
• Progesterone Receptor Positive
• Recurrent Breast Carcinoma
• Stage IIIB Breast Cancer AJCC v7
• Stage IIIC Breast Cancer AJCC v7
• Stage IV Breast Cancer AJCC v6 and v7

Intervention

Drug:
• Fulvestrant
Given IM

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Lapatinib Ditosylate
Given PO

Other:
• Placebo Administration
Given PO

Locations

Country	Name	City	State
United States	Avera Cancer Institute-Aberdeen	Aberdeen	South Dakota
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	Saint Anthony's Health	Alton	Illinois
United States	American Fork Hospital / Huntsman Intermountain Cancer Center	American Fork	Utah
United States	McFarland Clinic PC - Ames	Ames	Iowa
United States	AnMed Health Hospital	Anderson	South Carolina
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Hospital District Sixth of Harper County	Anthony	Kansas
United States	Arroyo Grande Community	Arroyo Grande	California
United States	PCR Oncology	Arroyo Grande	California
United States	Mission Hospital	Asheville	North Carolina
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Saint Agnes Hospital	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Baton Rouge General Medical Center	Baton Rouge	Louisiana
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana
United States	Mary Rutan Hospital	Bellefontaine	Ohio
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania
United States	University of Iowa Healthcare Cancer Services Quad Cities	Bettendorf	Iowa
United States	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	Saint Vincent Frontier Cancer Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Mid Dakota Clinic	Bismarck	North Dakota
United States	Saint Alexius Medical Center	Bismarck	North Dakota
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Boca Raton Regional Hospital	Boca Raton	Florida
United States	Saint Luke's Mountain States Tumor Institute	Boise	Idaho
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Saint Vincent's Medical Center	Bridgeport	Connecticut
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Aultman Health Foundation	Canton	Ohio
United States	Graham Hospital Association	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Missouri Hospital	Cape Girardeau	Missouri
United States	Memorial Hospital	Carthage	Illinois
United States	East Bay Radiation Oncology Center	Castro Valley	California
United States	Eden Hospital Medical Center	Castro Valley	California
United States	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California
United States	Sandra L Maxwell Cancer Center	Cedar City	Utah
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Saint Luke's Hospital	Chesterfield	Missouri
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
United States	Missouri Cancer Associates	Columbia	Missouri
United States	University of Missouri - Ellis Fischel	Columbia	Missouri
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Heartland Oncology and Hematology LLP	Council Bluffs	Iowa
United States	Danville Regional Medical Center	Danville	Virginia
United States	Genesis Cancer Care Institute	Davenport	Iowa
United States	Genesis Medical Center - East Campus	Davenport	Iowa
United States	Dayton Veterans Affairs Medical Center	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Heartland Cancer Research NCORP	Decatur	Illinois
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Capitol	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Saint Luke's Hospital of Duluth	Duluth	Minnesota
United States	Duke University Medical Center	Durham	North Carolina
United States	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York
United States	University of Maryland Shore Medical Center at Easton	Easton	Maryland
United States	Fairview-Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Elkhart Clinic	Elkhart	Indiana
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Bay Area Breast Surgeons Inc	Emeryville	California
United States	Green Bay Oncology - Escanaba	Escanaba	Michigan
United States	Eureka Hospital	Eureka	Illinois
United States	Saint Anne's Hospital	Fall River	Massachusetts
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Frederick Memorial Hospital	Frederick	Maryland
United States	Valley Medical Oncology Consultants-Fremont	Fremont	California
United States	Unity Hospital	Fridley	Minnesota
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	CaroMont Regional Medical Center	Gastonia	North Carolina
United States	Glendale Memorial Hospital and Health Center	Glendale	California
United States	Addison Gilbert Hospital	Gloucester	Massachusetts
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Goshen Center for Cancer Care	Goshen	Indiana
United States	Altru Cancer Center	Grand Forks	North Dakota
United States	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Mason District Hospital	Havana	Illinois
United States	Saint Rose Hospital	Hayward	California
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Maria Parham Hospital	Henderson	North Carolina
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Holland Community Hospital	Holland	Michigan
United States	New Hampshire Oncology Hematology PA-Hooksett	Hooksett	New Hampshire
United States	Hopedale Medical Complex - Hospital	Hopedale	Illinois
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Cleveland Clinic Cancer Center Independence	Independence	Ohio
United States	Community Cancer Center East	Indianapolis	Indiana
United States	Community Cancer Center North	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Mercyhealth Hospital and Cancer Center - Janesville	Janesville	Wisconsin
United States	Joliet Oncology-Hematology Associates Limited	Joliet	Illinois
United States	Freeman Health System	Joplin	Missouri
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Glacier Oncology PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Presence Saint Mary's Hospital	Kankakee	Illinois
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Keesler Medical Center	Keesler Air Force Base	Mississippi
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Kettering Medical Center	Kettering	Ohio
United States	Kewanee Hospital	Kewanee	Illinois
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee
United States	Vidant Oncology-Kinston	Kinston	North Carolina
United States	University of Tennessee - Knoxville	Knoxville	Tennessee
United States	Community Howard Regional Health	Kokomo	Indiana
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	AMITA Health Adventist Medical Center	La Grange	Illinois
United States	IU Health La Porte Hospital	La Porte	Indiana
United States	LRGHealthcare-Lakes Region General Hospital	Laconia	New Hampshire
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Saint Mary Medical and Regional Cancer Center	Langhorne	Pennsylvania
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Beebe Medical Center	Lewes	Delaware
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Southwest Medical Center	Liberal	Kansas
United States	Saint Rita's Medical Center	Lima	Ohio
United States	Meeker County Memorial Hospital	Litchfield	Minnesota
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Logan Regional Hospital	Logan	Utah
United States	Doctors Carrol, Sheth, Raghavan	Louisville	Kentucky
United States	Lowell General Hospital	Lowell	Massachusetts
United States	Southeastern Regional Medical Center	Lumberton	North Carolina
United States	Mcdonough District Hospital	Macomb	Illinois
United States	Dean Hematology and Oncology Clinic	Madison	Wisconsin
United States	Elliot Hospital	Manchester	New Hampshire
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	Fremont - Rideout Cancer Center	Marysville	California
United States	Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Loyola University Medical Center	Maywood	Illinois
United States	University of Tennessee Health Science Center	Memphis	Tennessee
United States	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana
United States	Mid-Michigan Medical Center - Midland	Midland	Michigan
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute	Minneapolis	Minnesota
United States	Trinity Cancer Care Center	Minot	North Dakota
United States	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana
United States	Community Medical Hospital	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Specialists	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Morristown Medical Center	Morristown	New Jersey
United States	Virtua Memorial	Mount Holly	New Jersey
United States	Northern Westchester Hospital	Mount Kisco	New York
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Skagit Valley Hospital	Mount Vernon	Washington
United States	El Camino Hospital	Mountain View	California
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	Cottonwood Hospital Medical Center	Murray	Utah
United States	Intermountain Medical Center	Murray	Utah
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	Mercy Health Partners-Hackley Campus	Muskegon	Michigan
United States	Yale University	New Haven	Connecticut
United States	Louisiana State University Health Science Center	New Orleans	Louisiana
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Licking Memorial Hospital	Newark	Ohio
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Bromenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center Foundation	Normal	Illinois
United States	Southwest VA Regional Cancer Center	Norton	Virginia
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Tumor Institute	Oakland	California
United States	Hematology and Oncology Associates-Oakland	Oakland	California
United States	Highland General Hospital	Oakland	California
United States	Tom K Lee Inc	Oakland	California
United States	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Ottumwa Regional Health Center	Ottumwa	Iowa
United States	Granville Medical Center	Oxford	North Carolina
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Pekin Hospital	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Hospital	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina
United States	Via Christi Hospital-Pittsburg	Pittsburg	Kansas
United States	Valley Care Health System - Pleasanton	Pleasanton	California
United States	Valley Medical Oncology Consultants	Pleasanton	California
United States	Portneuf Medical Center	Pocatello	Idaho
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	Duke Raleigh Hospital	Raleigh	North Carolina
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Reid Health	Richmond	Indiana
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	West Suburban Medical Center	River Forest	Illinois
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	OSF Saint Anthony Medical Center	Rockford	Illinois
United States	Person Memorial Hospital	Roxboro	North Carolina
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Dixie Medical Center Regional Cancer Center	Saint George	Utah
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Oncology Care Associates PLLC	Saint Joseph	Michigan
United States	Center for Cancer Care and Research	Saint Louis	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	Saint Joseph's Hospital - Healtheast	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Salinas Valley Memorial	Salinas	California
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Intermountain Health Care	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah
United States	Kaiser Permanente-San Diego Mission	San Diego	California
United States	UCSF Medical Center-Mount Zion	San Francisco	California
United States	Zuckerberg San Francisco General Hospital	San Francisco	California
United States	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California
United States	Kaiser Permanente Washington	Seattle	Washington
United States	Minor and James Medical PLLC	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Avera McKennan Hospital and University Health Center	Sioux Falls	South Dakota
United States	Medical X-Ray Center	Sioux Falls	South Dakota
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Evergreen Hematology and Oncology PS	Spokane	Washington
United States	Saint Margaret's Hospital	Spring Valley	Illinois
United States	Memorial Medical Center	Springfield	Illinois
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Staten Island University Hospital	Staten Island	New York
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Overlook Hospital	Summit	New Jersey
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas
United States	Smilow Cancer Hospital-Torrington Care Center	Torrington	Connecticut
United States	Munson Medical Center	Traverse City	Michigan
United States	Saint Francis Medical Center	Trenton	New Jersey
United States	Upper Valley Medical Center	Troy	Ohio
United States	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California
United States	Carle Cancer Center	Urbana	Illinois
United States	Northbay Cancer Center	Vacaville	California
United States	Inspira Medical Center Vineland	Vineland	New Jersey
United States	Virtua Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	Harold Leever Regional Cancer Center	Waterbury	Connecticut
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Woodwinds Health Campus	Woodbury	Minnesota
United States	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio
United States	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts
United States	Wright-Patterson Medical Center	Wright-Patterson Air Force Base	Ohio
United States	Metro Health Hospital	Wyoming	Michigan
United States	Greene Memorial Hospital	Xenia	Ohio
United States	York Hospital	York	Maine
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Progression-free Survival for Participants With HER2-negative Tumors	PFS was defined as the interval from study entry until disease progression or death resulting from any cause, which ever occurred first.	Up to 5 years
Other	Progression-free Survival for Participants With HER2-positive Tumors	PFS was defined as the interval from study entry until disease progression or death resulting from any cause, whichever occurred first.	Up to 5 years
Other	Objective Tumor Response Rate for Participants With HER2-negative Tumors	Response was defined by the RECIST. A responding participant had either a Complete Response (disappearance of all target lesions) or Partial Response (30% decrease in sum of longest diameter of target lesions). The response rate of measurable tumors will be estimated with its 95% confidence interval according to treatment arm.	Up to 5 years
Other	Objective Tumor Response Rate for Participants With HER2-positive Tumors	Response was defined by the RECIST. A responding participant had either a Complete Response (disappearance of all target lesions) or Partial Response (30% decrease in sum of longest diameter of target lesions). The response rate of measurable tumors will be estimated with its 95% confidence interval according to treatment arm.	Up to 5 years
Primary	Progression-free Survival (PFS)	PFS was defined as the interval from study entry until disease progression or death resulting from any cause, which ever occurred first. Progression is defined as a 20% increase in the sum of longest diameter of target lesions (per RECIST criteria).	Interval from randomization until disease progression or death, whichever occurs first, assessed up to 5 years
Secondary	Objective Tumor Response Rate	Response was defined by the Response Evaluation Criteria in Solid Tumors (RECIST). A responding participant had either a Complete Response (disappearance of all target lesions) or Partial Response (30% decrease in sum of longest diameter of target lesions). The response rate of measurable tumors will be estimated with its 95% confidence interval according to treatment arm.	Up to 5 years
Secondary	Overall Survival (OS)	Overall survival was measured as the interval from study entry until death, from any cause, or last contact.	Study entry to death or last follow-up, up to 5 years