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



Status:Suspended
Conditions:Breast Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:12/22/2018
Start Date:May 2014
End Date:May 2022

Use our guide to learn which trials are right for you!

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

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.

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.

- 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.
We found this trial at
223
sites
929 N St Francis St
Wichita, Kansas 67214
(316) 268-5775
Via Christi Regional Medical Center Via Christi Health's rich history of serving the people of...
?
mi
from
Wichita, KS
Click here to add this to my saved trials
234 Goodman Dr
Cincinnati, Ohio 45229
(513) 584-1000
University of Cincinnati Medical Center Opening in 1823 as the country
?
mi
from
Cincinnati, OH
Click here to add this to my saved trials
1 Hurley Plaza
Flint, Michigan 48503
(810) 262-9000
Hurley Medical Center From its founding in 1908, Hurley Medical Center has devoted itself to...
?
mi
from
Flint, MI
Click here to add this to my saved trials
2500 N State St
Jackson, Mississippi 39216
(601) 984-1000
University of Mississippi Medical Center The University of Mississippi Medical Center, located in Jackson, is...
?
mi
from
Jackson, MS
Click here to add this to my saved trials
529 West Markham Street
Little Rock, Arkansas 72205
(501) 686-7000
University of Arkansas for Medical Sciences The University of Arkansas for Medical Sciences (UAMS) in...
?
mi
from
Little Rock, AR
Click here to add this to my saved trials
4805 Northeast Glisan Street
Portland, Oregon 97213
(503) 215-1111
Providence Portland Medical Center We strive to give those we serve exceptional, compassionate health care...
?
mi
from
Portland, OR
Click here to add this to my saved trials
1100 Fairview Avenue North
Seattle, Washington 98109
(206) 667-5000
Fred Hutchinson Cancer Research Center At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of...
?
mi
from
Seattle, WA
Click here to add this to my saved trials
'Aiea, Hawaii 96701
?
mi
from
'Aiea, HI
Click here to add this to my saved trials
98-1079 Moanalua Road
'Aiea, Hawaii 96701
?
mi
from
'Aiea, HI
Click here to add this to my saved trials
?
mi
from
Amarillo, TX
Click here to add this to my saved trials
Anacortes, Washington 98221
?
mi
from
Anacortes, WA
Click here to add this to my saved trials
Anchorage, Alaska 99508
?
mi
from
Anchorage, AK
Click here to add this to my saved trials
Anchorage, Alaska 99508
?
mi
from
Anchorage, AK
Click here to add this to my saved trials
Anchorage, Alaska 99508
?
mi
from
Anchorage, AK
Click here to add this to my saved trials
Anchorage, Alaska 99508
?
mi
from
Anchorage, AK
Click here to add this to my saved trials
Anchorage, Alaska 99508
?
mi
from
Anchorage, AK
Click here to add this to my saved trials
Ann Arbor, Michigan 48106
?
mi
from
Ann Arbor, MI
Click here to add this to my saved trials
Ann Arbor, Michigan 48197
?
mi
from
Ann Arbor, MI
Click here to add this to my saved trials
Ann Arbor, Michigan 48109
?
mi
from
Ann Arbor, MI
Click here to add this to my saved trials
Auburn, Washington 98002
?
mi
from
Auburn, WA
Click here to add this to my saved trials
Bainbridge Island, Washington 98110
?
mi
from
Bainbridge Island, WA
Click here to add this to my saved trials
2401 W Belvedere Ave
Baltimore, Maryland 21215
(410) 601-9000
Sinai Hospital of Baltimore Sinai Hospital of Baltimore provides a broad array of high-quality, cost-effective...
?
mi
from
Baltimore, MD
Click here to add this to my saved trials
?
mi
from
Beachwood, OH
Click here to add this to my saved trials
Bellevue, Washington 98004
?
mi
from
Bellevue, WA
Click here to add this to my saved trials
?
mi
from
Bellevue, WA
Click here to add this to my saved trials
Bellingham, Washington 98225
?
mi
from
Bellingham, WA
Click here to add this to my saved trials
800 Farson Street
Belpre, Ohio 45714
(740) 401-0417
Strecker Cancer Center-Belpre The Memorial Health System's Strecker Cancer Center, Belpre combines the clinical expertise...
?
mi
from
Belpre, OH
Click here to add this to my saved trials
Bend, Oregon 97701
?
mi
from
Bend, OR
Click here to add this to my saved trials
Beverly, Massachusetts 01915
?
mi
from
Beverly, MA
Click here to add this to my saved trials
Billings, Montana 59101
?
mi
from
Billings, MT
Click here to add this to my saved trials
Billings, Montana 59101
?
mi
from
Billings, MT
Click here to add this to my saved trials
?
mi
from
Boise, ID
Click here to add this to my saved trials
1501 North Oakland Drive
Bolivar, Missouri 65613
417-326-7200
Central Care Cancer Center at Carrie J. Babb Cancer Center Cancer treatment often requires a...
?
mi
from
Bolivar, MO
Click here to add this to my saved trials
915 Highland Blvd
Bozeman, Montana 59715
(406) 414-5000
Bozeman Deaconess Hospital Bozeman Deaconess Hospital is a Joint Commission certified, licensed Level III trauma...
?
mi
from
Bozeman, MT
Click here to add this to my saved trials
Branson, Missouri 65616
?
mi
from
Branson, MO
Click here to add this to my saved trials
Bridgeport, Connecticut 06610
?
mi
from
Bridgeport, CT
Click here to add this to my saved trials
Bristol, Tennessee 37620
?
mi
from
Bristol, TN
Click here to add this to my saved trials
?
mi
from
Bristol, TN
Click here to add this to my saved trials
?
mi
from
Burbank, CA
Click here to add this to my saved trials
Burlington, Massachusetts 01805
?
mi
from
Burlington, MA
Click here to add this to my saved trials
?
mi
from
Butte, MT
Click here to add this to my saved trials
211 Saint Francis Drive
Cape Girardeau, Missouri 63701
?
mi
from
Cape Girardeau, MO
Click here to add this to my saved trials
Centralia, Illinois 62801
?
mi
from
Centralia, IL
Click here to add this to my saved trials
505 S Plummer Ave
Chanute, Kansas 66720
(620) 431-7580
Cancer Center of Kansas, PA - Chanute Dr. H.E. Hynes founded Cancer Center of Kansas,...
?
mi
from
Chanute, KS
Click here to add this to my saved trials
272 Hospital Rd
Chillicothe, Ohio 45601
740-779-7500
Adena Regional Medical Center Since 1895, Adena Health System has remained focused on its commitment...
?
mi
from
Chillicothe, OH
Click here to add this to my saved trials
Cincinnati, Ohio 45220
?
mi
from
Cincinnati, OH
Click here to add this to my saved trials
?
mi
from
Clackamas, OR
Click here to add this to my saved trials
9280 SE Sunnybrook Blvd #100
Clackamas, Oregon 97015
(503) 513-3300
Clackamas Radiation Oncology Center State-of-the-art technology and compassionate care come together at Clackamas Radiation Oncology...
?
mi
from
Clackamas, OR
Click here to add this to my saved trials
18101 Lorain Avenue
Cleveland, Ohio 44111
216.476.7000
Cleveland Clinic Cancer Center at Fairview Hospital Fairview Hospital is a 488-bed hospital located at...
?
mi
from
Cleveland, OH
Click here to add this to my saved trials
2049 E 100th St
Cleveland, Ohio 44106
(216) 444-2200
Cleveland Clinic Foundation The Cleveland Clinic (formally known as The Cleveland Clinic Foundation) is a...
?
mi
from
Cleveland, OH
Click here to add this to my saved trials
Clinton, North Carolina 28328
?
mi
from
Clinton, NC
Click here to add this to my saved trials
Cody, Wyoming 82414
?
mi
from
Cody, WY
Click here to add this to my saved trials
Coeur d'Alene, Idaho 83814
?
mi
from
Coeur d'Alene, ID
Click here to add this to my saved trials
?
mi
from
Columbus, OH
Click here to add this to my saved trials
Columbus, Ohio 43213
?
mi
from
Columbus, OH
Click here to add this to my saved trials
3100 Plaza Properties Blvd
Columbus, Ohio 43219
(614) 383-6000
The Mark H. Zangmeister Center At The Zangmeister Center, we appreciate that our patients have...
?
mi
from
Columbus, OH
Click here to add this to my saved trials
Columbus, Ohio 43222
?
mi
from
Columbus, OH
Click here to add this to my saved trials
Corona, California 92879
?
mi
from
Corona, CA
Click here to add this to my saved trials
?
mi
from
Dayton, OH
Click here to add this to my saved trials
?
mi
from
Dayton, OH
Click here to add this to my saved trials
Dayton, Ohio 45428
?
mi
from
Dayton, OH
Click here to add this to my saved trials
9000 N. Main St.
Dayton, Ohio 45415
(937) 734-6784
Samaritan North Health Center Good Samaritan Hospital (GSH) is passionate about providing the most recent...
?
mi
from
Dayton, OH
Click here to add this to my saved trials
Dearborn, Michigan 48124
?
mi
from
Dearborn, MI
Click here to add this to my saved trials
Decatur, Illinois 62526
?
mi
from
Decatur, IL
Click here to add this to my saved trials
2300 N Edward St
Decatur, Illinois 62526
(217) 876-8121
Decatur Memorial Hospital An American flag bearing only 48 stars waved above Decatur Memorial Hospital...
?
mi
from
Decatur, IL
Click here to add this to my saved trials
?
mi
from
Decatur, IL
Click here to add this to my saved trials
DeKalb, Illinois 60115
?
mi
from
DeKalb, IL
Click here to add this to my saved trials
Detroit, Michigan 48236
?
mi
from
Detroit, MI
Click here to add this to my saved trials
Detroit, Michigan 48202
?
mi
from
Detroit, MI
Click here to add this to my saved trials
2020 Central Ave
Dodge City, Kansas 67801
(620) 227-2488
Cancer Center of Kansas, PA - Dodge City Dr. H.E. Hynes founded Cancer Center of...
?
mi
from
Dodge City, KS
Click here to add this to my saved trials
1500 East Duarte Road
Duarte, California 91010
626-256-HOPE (4673)
City of Hope National Medical Center City of Hope is dedicated to making a difference...
?
mi
from
Duarte, CA
Click here to add this to my saved trials
Edmonds, Washington 98026
?
mi
from
Edmonds, WA
Click here to add this to my saved trials
Effingham, Illinois 62401
?
mi
from
Effingham, IL
Click here to add this to my saved trials
700 West Central
El Dorado, Kansas 67042
(316) 889-0099
Cancer Center of Kansas, PA - El Dorado Dr. H.E. Hynes founded Cancer Center of...
?
mi
from
El Dorado, KS
Click here to add this to my saved trials
Federal Way, Washington 98002
?
mi
from
Federal Way, WA
Click here to add this to my saved trials
302 Kensington Ave
Flint, Michigan 48503
(810) 762-8490
Genesys Hurley Cancer Institute Bringing the most advanced cancer treatment services, technologies and programs available...
?
mi
from
Flint, MI
Click here to add this to my saved trials
555 East Cheves Street
Florence, South Carolina 29506
843-777-2000
McLeod Regional Medical Center McLeod Health, a regional presence and predominant healthcare organization, is dedicated...
?
mi
from
Florence, SC
Click here to add this to my saved trials
Fort Scott, Kansas 66701
(620) 223-8589
Cancer Center of Kansas - Fort Scott Dr. H.E. Hynes founded Cancer Center of Kansas,...
?
mi
from
Fort Scott, KS
Click here to add this to my saved trials
Gaffney, South Carolina 29341
?
mi
from
Gaffney, SC
Click here to add this to my saved trials
Gig Harbor, Washington 98335
?
mi
from
Gig Harbor, WA
Click here to add this to my saved trials
?
mi
from
Gig Harbor, WA
Click here to add this to my saved trials
298 Washington St
Gloucester, Massachusetts 01930
(978) 283-4000
Addison Gilbert Hospital Addison Gilbert Hospital is a full service, 58-bed medical/surgical acute care facility....
?
mi
from
Gloucester, MA
Click here to add this to my saved trials
2700 Wayne Memorial Dr
Goldsboro, North Carolina 27534
(919) 736-1110
Wayne Memorial Hospital Wayne Memorial Hospital, an affiliate of Wayne Health Corporation, is home to...
?
mi
from
Goldsboro, NC
Click here to add this to my saved trials
Goldsboro, North Carolina 27534
?
mi
from
Goldsboro, NC
Click here to add this to my saved trials
Great Falls, Montana 59405
?
mi
from
Great Falls, MT
Click here to add this to my saved trials
835 Sweitzer St
Greenville, Ohio 45331
(937) 548-1141
Wayne Hospital Stretching back to our roots nearly 100 years ago, Wayne HealthCare has always...
?
mi
from
Greenville, OH
Click here to add this to my saved trials
Greer, South Carolina 29651
?
mi
from
Greer, SC
Click here to add this to my saved trials
Grosse Pointe, Michigan 48230
?
mi
from
Grosse Pointe, MI
Click here to add this to my saved trials
Hartford, Connecticut 06105
?
mi
from
Hartford, CT
Click here to add this to my saved trials
Helena, Montana 59601
?
mi
from
Helena, MT
Click here to add this to my saved trials
Hendersonville, North Carolina 28971
?
mi
from
Hendersonville, NC
Click here to add this to my saved trials
Hendersonville, North Carolina 28792
?
mi
from
Hendersonville, NC
Click here to add this to my saved trials
Hendersonville, North Carolina 28791
?
mi
from
Hendersonville, NC
Click here to add this to my saved trials
1319 Punahou St
Honolulu, Hawaii 96826
(808) 983-6000
Kapiolani Medical Center for Women and Children Hawai‘i Pacific Health is an integrated health care...
?
mi
from
Honolulu, HI
Click here to add this to my saved trials
Honolulu, Hawaii 96813
?
mi
from
Honolulu, HI
Click here to add this to my saved trials
321 N Kuakini St
Honolulu, Hawaii 96817
(808) 531-8521
Oncare Hawaii Inc-Kuakini OnCare Hawaii is a Certified PROVENGE® Treatment Center. PROVENGE (sipuleucel-T) is the...
?
mi
from
Honolulu, HI
Click here to add this to my saved trials
2226 Liliha St. Ste B-204
Honolulu, Hawaii 96817
808.536.4888
OnCare Hawaii-Liliha OnCare Hawaii is a Certified PROVENGE® Treatment Center. PROVENGE (sipuleucel-T) is the only...
?
mi
from
Honolulu, HI
Click here to add this to my saved trials
888 S King St
Honolulu, Hawaii 96813
(808) 522-4000
Straub Clinic And Hospital Founded in 1921, Straub Clinic & Hospital is a fully integrated...
?
mi
from
Honolulu, HI
Click here to add this to my saved trials
Honolulu, Hawaii 96813
?
mi
from
Honolulu, HI
Click here to add this to my saved trials
Honolulu, Hawaii 96813
?
mi
from
Honolulu, HI
Click here to add this to my saved trials
800 W. Laurel
Independence, Kansas 67301
620-331-4099
Cancer Center of Kansas-Independence Dr. H.E. Hynes founded Cancer Center of Kansas, P. A. in...
?
mi
from
Independence, KS
Click here to add this to my saved trials