NCT01674140|Active Not RecruitingPhase 3ResultsDMC

S1207 Hormone Therapy With or Without Everolimus in Treating Patients With Breast Cancer

Phase III Randomized, Placebo-Controlled Clinical Trial Evaluating the Use of Adjuvant Endocrine Therapy +/- One Year of Everolimus in Patients With High-Risk, Hormone Receptor-Positive and HER2/Neu Negative Breast Cancer

SWOG Cancer Research Network ClinicalTrials.gov

Compare

3 other identifiers

S1207U10CA032102NCI-2012-01995

Study Type

interventional

Target

1,939

Locations

2 countries

Sites

1459

Timeline

RegisteredAug 2012

StartedSep 2013

CompletionJan 2030

Brief Summary

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen citrate, goserelin acetate, leuprolide acetate, anastrozole, letrozole, or exemestane, may fight breast cancer by lowering the amount of estrogen the body makes. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet know whether hormone therapy is more effective when given with or without everolimus in treating breast cancer. PURPOSE: This randomized phase III trial studies how well giving hormone therapy together with or without everolimus work in treating patients with breast cancer.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

1,939

participants targeted

Target at P75+ for phase_3 breast-cancer

Timeline

45mo left

Started Sep 2013

Longer than P75 for phase_3 breast-cancer

Geographic Reach

2 countries

1459 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

16.3 years study duration

Study Progress78%

Sep 2013Jan 2030

First Submitted

Initial submission to the registry

August 24, 2012

Completed

4 days until next milestone

First Posted

Study publicly available on registry

August 28, 2012

Completed

1 year until next milestone

Study Start

First participant enrolled

September 12, 2013

Completed

9.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2022

Completed

1.1 years until next milestone

Results Posted

Study results publicly available

December 20, 2023

Completed

6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2030

Expected

Last Updated

February 10, 2026

Status Verified

January 1, 2026

Enrollment Period

9.2 years

First QC Date

August 24, 2012

Results QC Date

October 25, 2023

Last Update Submit

January 21, 2026

Conditions

Breast Cancer

Keywords

estrogen receptor-positive breast cancerHER2-negative breast cancerstage IA breast cancerstage IB breast cancerstage II breast cancerstage IIIA breast cancerstage IIIB breast cancerstage IIIC breast cancerprogesterone receptor-positive breast cancermale breast cancer

Outcome Measures

Primary Outcomes (1)

Invasive Disease-Free Survival (IDFS)
Time from date of registration to date of first invasive recurrence (local, regional or distant), second invasive primary cancer (breast or not), or death due to any cause. Patients last known to be alive who have not experienced recurrence or second primary cancer are censored at their last contact date. The results were presented as 5-year IDFS estimate.
Up to 5 years post registration

Secondary Outcomes (3)

Overall Survival (OS)
5 years after last accrual
Toxicity Based on Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0, Assessed up to 10 Years.
Every 6 weeks while on protocol therapy. Adverse events (AEs) that occurred during follow up after protocol treatment were reported as late AEs, for every 6 months for the first 2 years and then yearly until 10 years after registration.
Distant Recurrence-Free Survival (DRFS)
5 years after last accrual

Study Arms (2)

Arm I

PLACEBO COMPARATOR

Patients receive an approved endocrine therapy comprising tamoxifen citrate\*, goserelin acetate\*\* or leuprolide acetate\*\*, or an aromatase inhibitor (anastrozole, letrozole, or exemestane) for 2-5 years. Patients also receive a placebo PO daily for 1 year in the absence of disease progression or unacceptable toxicity.

Drug: anastrozoleDrug: exemestaneDrug: goserelin acetateDrug: letrozoleDrug: leuprolide acetateDrug: tamoxifen citrateOther: placebo

Arm II

EXPERIMENTAL

Patients receive an approved endocrine therapy regimen as in arm I. Patients also receive everolimus PO daily for 1 year in the absence of disease progression or unacceptable toxicity.

Drug: anastrozoleDrug: everolimusDrug: exemestaneDrug: goserelin acetateDrug: letrozoleDrug: leuprolide acetateDrug: tamoxifen citrate

Interventions

anastrozoleDRUG

Given orally

Also known as: Arimidex

Arm IArm II

everolimusDRUG

Given PO

Also known as: Afinitor

Arm II

exemestaneDRUG

Given orally

Also known as: Aromasin

Arm IArm II

goserelin acetateDRUG

Given subcutaneously or intramuscularly

Also known as: Zoladex

Arm IArm II

letrozoleDRUG

Given orally

Also known as: Femara

Arm IArm II

leuprolide acetateDRUG

Given subcutaneously or intramuscularly

Also known as: Lupron

Arm IArm II

tamoxifen citrateDRUG

Given PO

Also known as: nolvadex

Arm IArm II

placeboOTHER

Given PO

Arm I

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Patients must have a histologically confirmed diagnosis of invasive breast carcinoma with positive estrogen (ER)- and/or progesterone-receptor (PR) status, and negative human epidermal growth factor receptor (HER)2, for whom standard adjuvant endocrine therapy is planned * ER and PR positivity must be assessed according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines as either ER or PR ≥ 1% positive nuclear staining * HER2 test result negativity must be assessed as per ASCO/CAP 2013 guidelines using IHC, ISH or both. HER2 is negative if a single test (or all tests) performed in a tumor specimen show: 1. IHC negative (0 or 1+) 2. ISH negative using single probe or dual probe. If IHC is 2+, evaluation for gene amplification (ISH) must be performed and the ISH must be negative; ISH is not required if IHC is 0 or 1+. HER2 equivocal is not eligible. * Patients must not have metastatic breast cancer (stage IV disease); patients with multifocal, multicentric, and synchronous bilateral, and primary inflammatory breast cancers are allowed * Multifocal disease is defined as more than one invasive cancer \< 2 cm from the largest lesion within the same breast quadrant * Multicentric disease is defined as more than one invasive cancer ≥ 2 cm from the largest lesion within the same breast quadrant or more than one lesion in different quadrants * Synchronous bilateral disease is defined as invasive breast cancer with positive lymph nodes (axillary or intramammary) in at least one breast, diagnosed within 30 days of each other * Patients must be high risk by belonging to one of the following risk groups: * Completion of adjuvant chemotherapy and pathologically negative axillary nodes, and a tumor measuring ≥ 2 cm in greatest diameter, and an Oncotype DX® recurrence score (RS) \> 25 (completed as standard of care). Patients with micrometastases as the only nodal involvement (pN1mi) are eligible, and will be categorized as node-negative. * Completion of adjuvant chemotherapy, and pathologically 1-3 positive lymph nodes, and either an Oncotype DX® RS \> 25 (screened via S1007 or otherwise) or tumor tissue with pathological Grade III following local practice. If Oncotype DX is done, then RS must be \> 25. If the test is not done, but the patient has Grade III disease then the patient is eligible and Oncotype DX does not need to be performed. * Completion of adjuvant chemotherapy and pathologically 4 or more positive lymph nodes. * Completion of neoadjuvant chemotherapy and 1 or more positive nodes pathologically determined prior to or after chemotherapy * Patients must have completed either breast-conserving surgery or total mastectomy, with negative margins and appropriate axillary staging; a negative margin is defined as no evidence of tumor or ductal carcinoma in situ (DCIS) at the line of resection; additional operative procedures may be performed to obtain clear margins * Patients who had breast-conserving surgery must have completed whole-breast radiation; use of regional nodal-basin radiation will be at the discretion of the investigator according to institutional guidelines * Patients with ≥ 4 positive lymph nodes must have completed breast/chest wall and nodal-basin radiation therapy according to standard-of-care guidelines before randomization; omission of radiation therapy is not allowed in this high-risk population of patients * Patients must be registered no sooner than 21 days after completion of radiation therapy and must have recovered (≤ grade 1) from any of the effects of radiation * Patients must have undergone axillary staging by sentinel-node biopsy or axillary lymph node dissection (ALND) * For patients with 1-3 positive lymph nodes, sentinel-node biopsy alone is allowed provided that the patient completed either whole-breast or chest-wall radiation and the primary tumor is \< 5 cm * All patients with ≥ 4 positive lymph nodes must have completed ALND (with or without prior sentinel-node biopsy) PATIENT CHARACTERISTICS: * Absolute Neutrophil Count ≥ 1,500/mL * Hemoglobin ≥ 9 g/dL * Platelet count ≥ 100,000/mL * Bilirubin ≤ 1.5 mg/dL (≤ 3.0 mg/dL if due to Gilbert syndrome) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 times institutional upper limit of normal (IULN) * Alkaline phosphatase ≤ 1.5 times IULN * Serum creatinine level ≤ IULN * Fasting cholesterol ≤ 300 mg/dL and triglycerides ≤ 2.5 times IULN; patients may be on lipid-lowering agents to reach these values * 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 previously diagnosed with diabetes must not have uncontrolled diabetes (defined as a hemoglobin \[Hg\] A1C \> 7% within 28 days prior to registration) * Patients known to be human immunodeficiency virus (HIV) positive may be enrolled if baseline CD4 count is \> 500 cells/mm³ and they are not taking anti-retroviral therapy * Patients with known hepatitis are not eligible * Patients must not have any known uncontrolled, underlying pulmonary disease * Patients must be able to take oral medications * Patients may not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of blinded drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) * Patients must not be pregnant or nursing * Women/men of reproductive potential must have agreed to use an effective non-hormonal contraceptive method during and for 8 weeks after completion of study therapy * In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; corresponding procedures for men include castration, vasectomy, and barrier-contractive devices * If at any point a previously celibate patient chooses to become heterosexually active during the protocol therapy, he/she is responsible for beginning contraceptive measures * 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 PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Patients must have completed standard neoadjuvant or adjuvant chemotherapy prior to randomization; completion of chemotherapy will be determined by the treating oncologist, but should include a minimum of 4 cycles (a cycle of weekly paclitaxel is considered 3 doses); patients must be registered within 42 weeks after the last dose of chemotherapy; patients may have started endocrine therapy at any time after the diagnosis of the current breast cancer * Patients must not be receiving or planning to receive trastuzumab * Concurrent bisphosphonate therapy is allowed * Patients must not have prior exposure to mTOR inhibitors (rapamycin, everolimus, temsirolimus, deforolimus) * Patients must not have prior treatment with any investigational drug within the preceding 28 days and must not be planning to receive any other investigational drug for the duration of the study * Patients must not be planning to receive any other anticancer drug for the duration of the study * 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 must not have received immunization with an attenuated live vaccine (e.g., intranasal influenza, measles, mumps, and rubella \[MMR\], oral polio, varicella, zoster, yellow fever, and Bacillus Calmette-Guérin \[BCG\] 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 cytochrome P450 3A4 (CYP3A4) inhibitors and/or CYP3A4 inducers

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

National Cancer Institute (NCI)collaborator
SWOG Cancer Research Networklead

Study Sites (1459)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC