S1222 Trial (Everolimus, Anastrozole and Fulvestrant) in Post-Menopausal Stage IV Breast Cancer

Breast Cancer Clinical Trial

Official title:

Fulvestrant Alone Versus Fulvestrant and Everolimus Versus Fulvestrant, Everolimus and Anastrozole: A Phase III Randomized Placebo-Controlled Trial in Postmenopausal Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02137837
• Other study ID #: S1222
• Status: Terminated
• Phase: Phase 3
• Start date: May 2014
• Est. completion date: December 31, 2019

Study information

• Verified date: January 2021
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized Phase III trial studies how well the combination of fulvestrant and everolimus together or the combination of anastrozole, fulvestrant and everolimus together, improve progression-free survival (PFS) versus fulvestrant alone.

Description:

OBJECTIVES: Primary - To test the benefit of interfering with the function of the estrogen receptor (ER) and providing downstream target inhibition (PI3K/AKT/mTOR) with a combination of optimal dose fulvestrant and everolimus (Arm 2) to improve progression-free survival compared to the optimal dose fulvestrant alone (Arm 1). - To test the benefit of adding the non-steroidal aromatase inhibitor anastrozole to optimal dose fulvestrant and everolimus (Arm 3) in order to improve progression free survival over optimal dose fulvestrant (Arm 1). Secondary - To compare progression-free survival among those receiving fulvestrant + everolimus + anastrozole (Arm 3) versus fulvestrant + everolimus (Arm 2). - To compare overall survival among the treatment arms in post-menopausal patients with hormone-receptor positive (HR+) Stage IV breast cancer. - To assess and compare toxicities, feasibility and compliance among the study regimens. - To compare response rates and clinical benefit rates among the study regimens. - To test molecular determinants of response to endocrine therapy and everolimus in circulating tumor cells: 1. CTC-Endocrine Therapy Index (CTC ETI) on the CellSearch® platform. 2. CTC-Next Generation Sequencing Analysis (CTC-NGS) of single cells captured on the HD-CTC® platform. OUTLINE: This is a multicenter study. Patients will be stratified according to the following factors: - Measurable versus evaluable non-measurable disease - Prior adjuvant hormonal therapy completed more than 5 years ago vs. prior adjuvant hormonal therapy completed 1-5 years ago vs. de novo presentation of metastatic disease or no prior adjuvant hormonal therapy. ARMS: - Arm 1: fulvestrant + placebo (everolimus) + placebo (anastrozole) - Arm 2: fulvestrant + everolimus + placebo (anastrozole) - Arm 3: fulvestrant + everolimus + anastrozole Blood and tissue samples are collected for correlative science studies. After completion of study treatment, patients are followed up every 6 months for 2 years and then yearly thereafter for 5 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 37
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

• Patients must have a histologically confirmed diagnosis of invasive breast carcinoma with positive estrogen and/or progesterone receptor status, and negative human epidermal growth factor receptor (HER-2), for whom endocrine therapy is planned.
• The HER-2 test result is negative (and should be reported as such), if a single test

(or all tests)performed in a tumor specimen show:

• Immunohistochemistries (IHC) 1+ negative or IHC 0 negative or
• in situ hybridization (ISH) negative using a single probe ISH or dual probe ISH.
• Estrogen receptor (ER) and progesterone receptor (PgR) positivity must be assessed according to American Society of Clinial Oncology (ASCO)/College of American Physicians (CAP) guidelines as either ER or PR = 1% positive nuclear staining. If HER2 IHC is 2+, an evaluation for gene amplification must be performed and the gene must not be amplified. Gene amplification evaluation is not required if evaluation by IHC is 0 or 1+ by institutional standards.
• Patients must be post-menopausal women with a confirmed diagnosis of metastatic breast cancer (M1). Pathologic confirmation of histology is preferable. In the case of bone metastases only, biopsy-proven metastatic disease of solitary site, or multiple sites of involvement are required. Post-menopausal is defined by one of the following criteria as per National Comprehensive Cancer Network (NCCN) guidelines Version 3.

2013:

• Prior bilateral oophorectomy and/or hysterectomy
• Patients = 60 years of age
• Patients < 60 years of age and amenorrheic for = 12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression and follicle-stimulating hormone (FSH) and estradiol in the post-menopausal range
• Patients < 60 years of age taking tamoxifen or toremifene must have FSH and plasma estradiol levels within post-menopausal ranges
• Patients must have measurable or evaluable disease. Patients must have a chest and abdominal computerized tomography (CT) and bone scan within 28 days prior to registration. All scans needed for assessment of measurable disease must be performed within 28 days prior to registration. Evaluable disease must be assessed within 28 days prior to registration
• Patients with a history of prior chemotherapy or hormone therapy or immunotherapy for recurrent or metastatic disease are NOT eligible. Prior adjuvant or neoadjuvant chemotherapy if completed more than 12 months prior to registration is acceptable. Any number of prior hormonal therapy regimens for the adjuvant setting but not for metastatic or recurrent disease is allowed; prior adjuvant or neoadjuvant treatment with an aromatase inhibitor (e.g. anastrozole, letrozole, exemestane) is allowed, if completed more than 12 months prior to randomization.
• Patients who have taken luteinizing hormone-releasing hormone (LHRH) analogue as adjuvant therapy are eligible provided they have a) discontinued such therapy at least 12 months prior to registration AND b) have not resumed their menstrual periods.
• Patients must not have had prior exposure to fulvestrant or mTOR inhibitors (e.g., rapamycin, everolimus, temsirolimus, deforolimus). Concurrent bisphosphonate therapy is allowed. Patients must not have prior treatment with any investigational drug within 28 days prior to registration and must not be planning to receive any other investigational drug for the duration of the study.
• Patients must have an International Normalized Ratio (INR) = 1.6 within 28 days prior to registration.
• Patients must have adequate bone marrow function, as defined by Absolute Neutrophil Count (ANC) of = 1,500/mL, hemoglobin = 9 g/dL and a peripheral platelet count = 100,000/ mL, all within 28 days prior to registration.
• Patients must have adequate hepatic function obtained within 28 days prior to

registration and documented by all of the following:

• Bilirubin = 1.5 mg/dL (or = 3.0 mg/dL if due to Gilbert's Syndrome)
• alanine aminotransferase (ALT) (SGPT) and aspartate aminotransferase (AST) (SGOT) = 2.5 x Institutional Upper Limit of Normal (IULN), or = 5 x IULN if hepatic metastases are present.
• Patients must have adequate renal function with serum creatinine level = IULN within 28 days prior to registration.
• Patients must have a fasting cholesterol = 300 mg/dL and triglycerides = 2.5 x IULN obtained within 28 days prior to registration. Patients may be on lipid lowering agents to reach these values.
• Patients must have a complete history and physical examination within 28 days prior to registration.
• Patients with bleeding diathesis (i.e., disseminated intravascular coagulation [DIC], clotting factor deficiency) or long-term anti-coagulant therapy (other than antiplatelet therapy) are NOT eligible.
• Patients with presence of life-threatening metastatic visceral disease, defined as extensive hepatic involvement, or any degree of brain or leptomeningeal involvement (past or present), or symptomatic pulmonary lymphangitic spread are not eligible. Patients with discrete pulmonary parenchymal metastases are eligible, provided their respiratory function is not significantly compromised as a result of disease in the opinion of the investigator.
• Patients must have a performance status of 0 - 2 by Zubrod criteria.
• Patients must not have any Grade III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., patients with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia.
• Patients must not have uncontrolled diabetes (defined as an Hg A1C >7% within 28 days prior to registration).
• Patients must not have an organ allograft or other history of immune compromise. Patients must not be receiving chronic, systemic treatment with corticosteroids or other immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
• Patients known to be HIV positive may be enrolled if baseline CD4 count is > 500 cells/mm3 AND not taking anti-retroviral therapy. Patients with known chronic or active hepatitis are not eligible. Patients must not have any known uncontrolled underlying pulmonary disease.
• Patients must be able to take oral medications. Patient may not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
• Patients must not have received immunization with an attenuated live vaccine (e.g. intranasal influenza, MMR, oral polio, varicella, zoster, yellow fever and BCG vaccines) within seven days prior to registration nor have plans to receive such vaccination while on protocol treatment.
• Patients must not have taken within 14 days prior to registration, be taking, nor plan to take while on protocol treatment, strong CYP3A4 inhibitors, and/or CYP3A4 inducers.
• No other prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or other cancer for which the patient has been disease-free for 5 years.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Fulvestrant

• Anastrozole

• Everolimus

• Placebo - Anastrozole

• Placebo - Everolimus

Locations

Country	Name	City	State
United States	Oncare Hawaii, Inc - Pali Momi	'Aiea	Hawaii
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Don and Sybil Harrington Cancer Center	Amarillo	Texas
United States	Island Hospital	Anacortes	Washington
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	St. Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	Auburn Regional Medical Center	Auburn	Washington
United States	Virginia Mason Bainbridge Island Medical Center	Bainbridge Island	Washington
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Cleveland Clinic Cancer Center - Beachwood	Beachwood	Ohio
United States	Overlake Hospital Medical Center	Bellevue	Washington
United States	Swedish Cancer Inst-Eastside Oncology Hematoly	Bellevue	Washington
United States	PeaceHealth St. Joseph Medical Center	Bellingham	Washington
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	St. Charles Health System	Bend	Oregon
United States	Beverly Hospital	Beverly	Massachusetts
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	St. Alphonsus Regional Medical Center	Boise	Idaho
United States	Central Care Cancer Ctr-Carrie J. Babb Cancer Ctr	Bolivar	Missouri
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Cox Cancer Center Branson	Branson	Missouri
United States	Bridgeport Hospital	Bridgeport	Connecticut
United States	Wellmont Bristol Regional Medical Center	Bristol	Tennessee
United States	Wellmont Medical Associates Oncology and Hematology	Bristol	Tennessee
United States	Providence St. Joseph Medical Ctr/Disney Family CC	Burbank	California
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	St. James Community Hosp and Cancer Treatment Center	Butte	Montana
United States	St. Francis Medical Center	Cape Girardeau	Missouri
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	VA Medical Center - Cincinnati	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Oncology and Hematology Care Southeast	Clackamas	Oregon
United States	Cleveland Clinic Cancer Center - Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Medical Center	Coeur d'Alene	Idaho
United States	Columbus NCI Community Oncology Research Program	Columbus	Ohio
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	The Mark H. Zangmeister Center	Columbus	Ohio
United States	City of Hope-Corona	Corona	California
United States	Dayton NCI Community Oncology Research Program	Dayton	Ohio
United States	Good Samaritan Hospital and Health Center	Dayton	Ohio
United States	Samaritan North Health Center	Dayton	Ohio
United States	VA Medical Center - Dayton	Dayton	Ohio
United States	Oakwood Healthcare, Inc.	Dearborn	Michigan
United States	Cancer Care Specialists of Central Illinois	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Heartland Cancer Research NCORP	Decatur	Illinois
United States	Kishwaukee Community Hospital	DeKalb	Illinois
United States	St. John Hospital and Medical Center	Detroit	Michigan
United States	Wayne State University Medical Center	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	City of Hope National Medical Center	Duarte	California
United States	Swedish Medical Center - Edmonds	Edmonds	Washington
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Virginia Mason Federal Way Medical Center	Federal Way	Washington
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Gibbs Cancer Center-Gaffney	Gaffney	South Carolina
United States	MultiCare Gig Harbor Medical Park	Gig Harbor	Washington
United States	Tacoma/Valley Radiation Oncology Ctrs-Gig Harbor	Gig Harbor	Washington
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	Benefis Healthcare West Campus	Great Falls	Montana
United States	Wayne Hospital	Greenville	Ohio
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	William Beaumont Hospital-Grosse Pointe	Grosse Pointe	Michigan
United States	St. Francis Hospital and Medical Center	Hartford	Connecticut
United States	St. Peter's Community Hospital	Helena	Montana
United States	Hendersonville Hematology and Oncology at Pardee	Hendersonville	North Carolina
United States	Margaret R. Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Park Ridge Health	Hendersonville	North Carolina
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Oncare Hawaii Inc-POB I	Honolulu	Hawaii
United States	Oncare Hawaii, Inc - Kuakini	Honolulu	Hawaii
United States	Oncare Hawaii, Inc - Liliha	Honolulu	Hawaii
United States	Oncare Hawaii, Inc - POB II	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	Cancer Center of Kansas - Independence	Independence	Kansas
United States	Cleveland Clinic Cancer Center - Independence	Independence	Ohio
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Allegiance Health	Jackson	Michigan
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	Wellmont Medical Assoc Onc and Hem-Johnson City	Johnson City	Tennessee
United States	Mercy Hospital - Joplin	Joplin	Missouri
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	CHI Health Good Samaritan Hospital	Kearney	Nebraska
United States	Kettering Medical Center	Kettering	Ohio
United States	Cancer Center of Kansas - Kingman	Kingman	Kansas
United States	Holston Valley Hospital and Medical Center	Kingsport	Tennessee
United States	Wellmont Medical Assoc Onc and Hem-Kingsport	Kingsport	Tennessee
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	City of Hope Antelope Valley	Lancaster	California
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Sparrow Health System	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Cancer Center of Kansas - Liberal	Liberal	Kansas
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	PeaceHealth St. John Medical Center	Longview	Washington
United States	Virginia Mason Lynnwood Medical Center	Lynnwood	Washington
United States	Cleveland Clinic Cancer Center - Mansfield	Mansfield	Ohio
United States	De Soto Regional Medical Center	Mansfield	Louisiana
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Loyola University Stritch School of Medicine	Maywood	Illinois
United States	Marjorie Weinberg Cancer Center	Melrose Park	Illinois
United States	MidMichigan Medical Center - Midland	Midland	Michigan
United States	Community Medical Center	Missoula	Montana
United States	St. Patrick Hospital	Missoula	Montana
United States	University Health Conway	Monroe	Louisiana
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Yale University	New Haven	Connecticut
United States	Licking Memorial Hospital	Newark	Ohio
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Yale-New Haven Hospital North Haven Medical Center	North Haven	Connecticut
United States	Southwest Virginia Cancer Center	Norton	Virginia
United States	Bay Area Tumor Institute	Oakland	California
United States	Epic Care - Oakland	Oakland	California
United States	Summit Medical Center	Oakland	California
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Sacred Heart Hospital	Pensacola	Florida
United States	St Joseph Mercy Hospital - Oakland	Pontiac	Michigan
United States	St. Joseph Mercy Port Huron	Port Huron	Michigan
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kootenai Cancer Center	Post Falls	Idaho
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	Tacoma/Valley Radiation Oncology Ctrs-Puyallup	Puyallup	Washington
United States	Reid Hospital and Health Care Services	Richmond	Indiana
United States	Mercy Clinic Care and Hematology - Rolla	Rolla	Missouri
United States	PCRMC Bond Clinic	Rolla	Missouri
United States	Phelps County Regional Medical Center	Rolla	Missouri
United States	Beaumont Children's Hospital-Royal Oak	Royal Oak	Michigan
United States	Beaumont NCI Community Oncology Research Program	Royal Oak	Michigan
United States	St. Mary's Health System	Saginaw	Michigan
United States	Christian Hospital	Saint Louis	Missouri
United States	Mercy Hospital St. Louis	Saint Louis	Missouri
United States	St. Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	University of Utah Medical Center	Salt Lake City	Utah
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	North Coast Cancer Care, Inc.	Sandusky	Ohio
United States	Virginia G. Piper Cancer Center	Scottsdale	Arizona
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Cooperative-Seattle	Seattle	Washington
United States	Minor and James Medical, PLLC	Seattle	Washington
United States	Pacific Cancer Research Consortium NCORP	Seattle	Washington
United States	Pacific Medical Center - First Hill	Seattle	Washington
United States	Swedish Medical Center	Seattle	Washington
United States	Swedish Medical Center - Ballard Campus	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Welch Cancer Center - Sheridan Memorial Hospital	Sheridan	Wyoming
United States	Highland Clinic	Shreveport	Louisiana
United States	Louisiana State University Health Sciences Center	Shreveport	Louisiana
United States	City of Hope South Pasadena	South Pasadena	California
United States	Spartanburg Medical Cancer	Spartanburg	South Carolina
United States	Cancer Research for the Ozarks NCORP	Springfield	Missouri
United States	Central Illinois Hematology Oncology Center	Springfield	Illinois
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Springfield Clinic	Springfield	Illinois
United States	Springfield Regional Cancer Center	Springfield	Ohio
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Cleveland Clinic Strongsville Family Health Center	Strongsville	Ohio
United States	Cancer Care Specialists of Illinois-Swansea	Swansea	Illinois
United States	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington
United States	Multicare Health System	Tacoma	Washington
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Northwest NCI Community Oncology Research Program	Tacoma	Washington
United States	Tacoma/Valley Radiation Oncology Ctrs-Jackson Hill	Tacoma	Washington
United States	Tacoma/Valley Radiation Oncology Ctrs-Saint Joe's	Tacoma	Washington
United States	Beaumont Hospital, Troy Campus	Troy	Michigan
United States	Upper Valley Medical Centers	Troy	Ohio
United States	Southern Arizona VA Health Care System	Tucson	Arizona
United States	University of Arizona Cancer Center - North Campus	Tucson	Arizona
United States	University of Arizona Cancer Center - Orange Grove	Tucson	Arizona
United States	University of Arizona Medical Center - Univ Campus	Tucson	Arizona
United States	MGC Hematology Oncology-Union	Union	South Carolina
United States	South Georgia Medical Center - Pearlman Cancer Ctr	Valdosta	Georgia
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	St. John Macomb Hospital	Warren	Michigan
United States	South Pointe Hospital	Warrensville Heights	Ohio
United States	Mercy Hospital Washington	Washington	Missouri
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	St. Ann's Hospital	Westerville	Ohio
United States	Cleveland Clinic - Weston	Weston	Florida
United States	Associates in Women's Health	Wichita	Kansas
United States	Cancer Center of Kansas - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Wichita NCI Community Oncology Research Program	Wichita	Kansas
United States	Southeastern Medical Oncology Center-Wilson	Wilson	North Carolina
United States	Wilson Medical Center	Wilson	North Carolina
United States	Winchester Hospital	Winchester	Massachusetts
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Cleveland Clinic Cancer Center - Wooster	Wooster	Ohio
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
Southwest Oncology Group	AstraZeneca, Novartis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (Fulvestrant vs Fulvestrant + Everolimus )	From date of registration to date of first documentation of progression or death due to any cause. Participants last known to be alive are censored at date of last contact.	up to 5 years
Primary	Progression-free Survival (Fulvestrant Versus Fulvestrant + Everolimus + Anastrozole)	From date of registration to date of first documentation of progression or death due to any cause. Participants last known to be alive without report of progression are censored at date of last contact.	up to 5 years
Secondary	Progression Free Survival (Fulvestrant + Everolimus vs Fulvestrant + Everolimus + Anastrozole)	From date of registration to date of first documentation of progression or death due to any cause. Participants last known to be alive without report of progression are censored at date of last contact.	up to 5 years
Secondary	Overall Survival	From date of registration to date of death due to any cause. Participants last known to be alive without report of progression are censored at date of last contact.	up to 5 years
Secondary	Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs	Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.	Duration of treatment and follow up until death or 5 years post registration
Secondary	Response Rate	Proportion of participants who have confirmed or unconfirmed partial or complete response to therapy	assessed every 12 weeks, up to 5 years
Secondary	Clinical Benefit Rate	Proportion of participants who have confirmed and unconfirmed partial response, complete response or stable disease.	assessed every 12 weeks, up to 5 years
Secondary	Molecular Determinants of Response in Circulating Tumor Cells: CTC-ETI	CTC-Endocrine Therapy Index (CTC-ETI) on the CellSearch® platform. Based on enumeration of CTC/7.5 mL of whole blood, with >= 5 being elevated. (Due to limited samples collected, full analysis was not able to be performed as planned, so outcome measure reported here is number with elevated Day 1 CTC.)	Day 1, Day 29, time of progression (Day 29 to be collected only if Day 1 CTC was elevated.)