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

Registration Number
NCT01674140
Lead Sponsor
SWOG Cancer Research Network
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.

Detailed Description

OBJECTIVES:

Primary

* To compare whether the addition of one year of everolimus (10 mg daily) to standard adjuvant endocrine therapy improves invasive disease-free survival (IDFS) in patients with high-risk, hormone-receptor (HR)-positive, and human epidermal growth factor receptor (HER)2-negative breast cancer.

Secondary

* To compare whether the addition of one year of everolimus to standard adjuvant endocrine therapy improves overall survival (OS) and distant recurrence-free survival (DRFS) in this patient population.

* To evaluate the safety, toxicities, and tolerability of one year of everolimus in combination with standard adjuvant endocrine therapy and to compare it with standard adjuvant endocrine therapy plus placebo in this patient population.

* To determine whether the benefit of one year of everolimus use in addition to standard adjuvant endocrine therapy varies by recurrence score (RS), nodal status, or other commonly used prognostic factors.

* To evaluate adherence to 1-year treatment of everolimus in comparison to placebo in addition to standard adjuvant endocrine therapy in this patient population.

* To collect specimens in order to evaluate biomarkers of therapeutic efficacy. (exploratory)

OUTLINE: This is a multicenter study. Patients are stratified according to risk level (node-negative and recurrence score \[RS\] \> 25 in the primary tumor, and a tumor measuring ≥ 2 cm in greatest diameter treated with adjuvant therapy vs 1-3 positive lymph nodes and RS \> 25 treated with adjuvant therapy vs ≥ 4 positive lymph nodes \[any RS value\] treated with adjuvant therapy vs ≥ 4 positive lymph nodes \[any RS value\] prior to or after neoadjuvant chemotherapy). Patients are randomized to 1 of 2 treatment arms.

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

* Arm II: 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.

NOTE: \*Men receive tamoxifen citrate PO for 5 years.

NOTE: \*\*Goserelin acetate or leuprolide acetate is given if patient is or becomes postmenopausal.

Blood and tissue samples are collected for biomarker studies.

After completion of study treatment, patients are followed up every 6 months for 2 years and then yearly thereafter for 10 years.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
1939
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm IIleuprolide acetatePatients 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.
Arm IIgoserelin acetatePatients 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.
Arm Igoserelin acetatePatients 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.
Arm Itamoxifen citratePatients 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.
Arm IplaceboPatients 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.
Arm Ileuprolide acetatePatients 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.
Arm IItamoxifen citratePatients 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.
Arm IIanastrozolePatients 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.
Arm IIeverolimusPatients 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.
Arm IanastrozolePatients 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.
Arm IexemestanePatients 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.
Arm IIexemestanePatients 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.
Arm IletrozolePatients 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.
Arm IIletrozolePatients 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.
Primary Outcome Measures
NameTimeMethod
Invasive Disease-Free Survival (IDFS)Up to 5 years post registration

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.

Secondary Outcome Measures
NameTimeMethod
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.

Toxicity based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Only adverse events that are possibly, probably, or definitely related to study drug are reported.

Overall Survival (OS)5 years after last accrual

Time from date of registration to date of death due to any cause. Patients last known to be alive are censored at their last contact date. The results were presented as 5-year OS estimate.

Distant Recurrence-Free Survival (DRFS)5 years after last accrual

Time from date of registration to date of invasive distant disease recurrence, second invasive primary cancer (breast or not) or death due to any cause. Patients last known to be alive who have not experienced distant recurrence, or second primary cancer are censored at their last contact date. The results were presented as 5-year DRFS estimate.

Trial Locations

Locations (1448)

University of Alabama at Birmingham Cancer Center

🇺🇸

Birmingham, Alabama, United States

Anchorage Associates in Radiation Medicine

🇺🇸

Anchorage, Alaska, United States

Anchorage Radiation Therapy Center

🇺🇸

Anchorage, Alaska, United States

Alaska Breast Care and Surgery LLC

🇺🇸

Anchorage, Alaska, United States

Alaska Oncology and Hematology LLC

🇺🇸

Anchorage, Alaska, United States

Alaska Regional Hospital

🇺🇸

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

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University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States

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