Everolimus Combined With Anti-estrogen Therapy in Hormone-Receptor-Positive HER-2 Negative Advanced Breast Cancer

NCT02291913 | Completed Phase 2 Results FDA Drug

• 1 other identifier: SCRI BRE 212
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 8

Brief Summary

Many patients with ER-positive or PR-positive breast cancer are treated with endocrine therapy. Although most ER/PR-positive tumors initially respond to hormonal therapy, patients often experience disease progression. Everolimus, in combination with exemestane, has shown activity in endocrine-resistant disease. This study will evaluate the efficacy of Everolimus+ anti-estrogen therapy in patients with ER-positive metastatic breast cancer who have progressed after receiving anti-estrogen therapy.

Conditions

Breast Cancer

Keywords

ER-Positive Breast Cancer; HER2-Negative Breast Cancer; everolimus; anti-estrogen therapy; PR-Positive Breast Cancer; Afinitor

Outcome Measures

Primary Outcomes (1)

• Median Progression Free Survival (PFS)

  PFS is defined as the time from Day 1 of study drug administration to disease progression as defined by RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1 criteria, or death on study. Participants who are alive and free from disease progression will be censored at the date of last radiologic tumor assessment. Participants who receive non-protocol therapy (subsequent therapy) prior to incurring an event will be censored at the date of last tumor assessment prior to the start of subsequent therapy. Participants who do not have a post-baseline tumor assessment will be censored at the date of first treatment (Day 1).

  up to 3 years

Secondary Outcomes (5)

• Number of Patients With Adverse Events (AEs) as a Measure of Safety and Tolerability

  Up to 20 months

• Number of Patients With an Objective Response (CR or PR) Also Called the Overall Response Rate (ORR).

  every 8 weeks until discontinuation, up to 20 months

• Number of Participants With CR, PR, or 6 Months of SD Also Called Clinical Benefit Rate (CBR)

  Up to 20 months

• Median Time From First Occurrence of CR or PR to Disease Progression or Death Also Called Duration of Response (DOR)

  every 8 weeks until discontinuation, up to 20 months

• Median Overall Survival (OS)

  up to 3 years from first treatment

Study Arms (1)

everolimus

EXPERIMENTAL

Everolimus will be administered at a dose of 10 mg PO daily combined with any one of the following anti-estrogen therapies on which the patient most recently progressed (tamoxifen, fulvestrant, anastrozole, letrozole, exemestane, toremifine, or LHRH agonists in conjunction with anti-estrogen therapy). Anti-estrogen therapy will be administered at the US Food and Drug Administration (FDA) prescribed doses.

Drug: Everolimus; Drug: Exemestane; Drug: Tamoxifen; Drug: Fulvestrant; Drug: Anastrozole; Drug: Letrozole; Drug: Toremifine

Interventions

Everolimus DRUG

Also known as: Afinitor

everolimus

Exemestane DRUG

Anti-estrogen therapy

everolimus

Tamoxifen DRUG

Anti-estrogen therapy

everolimus

Fulvestrant DRUG

Anti-estrogen therapy

everolimus

Anastrozole DRUG

Anti-estrogen therapy

everolimus

Letrozole DRUG

Anti-estrogen therapy

everolimus

Toremifine DRUG

Anti-estrogen therapy

everolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic diagnosis of unresectable, locally recurrent or MBC.
• ER and/or PR-positive tumors with staining by immunohistochemistry (IHC) based on the most recent biopsy.
• Only 1 previous chemotherapy regimen for MBC. Patients progressing while receiving adjuvant endocrine therapy or progressing \<12 months from completion of adjuvant endocrine therapy are eligible.
• Progressed on anti-estrogen therapy (tamoxifen, fulvestrant, anastrozole, letrozole, exemestane, toremifine, or LHRH agonists in conjunction with anti-estrogen therapy) defined as:
• Recurrence while on, or within 12 months of end of anti-estrogen therapy for early stage breast cancer, or
• Progression while on, or within one month of anti-estrogen therapy for locally advanced or metastatic breast cancer.
• Note: No washout for anti-estrogen therapy required. Anti-estrogen therapy does not have to be the last treatment prior to study entry.
• Post-menopausal or pre/peri-menopausal women on tamoxifen. LHRH agonists may be used to render ovarian suppression with postmenopausal ranges of estradiol or FSH per institutional guidelines.
• HER2-negative breast cancer, defined as follows:
• Fluorescent In Situ Hybridization (FISH)-negative (FISH ratio \<2.0), or
• IHC 0-1+, or
• IHC 2-3+ AND FISH-negative (FISH ratio \<2.0).
• Measureable disease as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 or evaluable bone lesions, lytic or mixed, in absence of measureable disease by RECIST criteria.
• Adequate hematologic, hepatic and renal function.
• International normalized ratio (INR) ≤1.5 or prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits (WNL) of the institution (if patient is not on anti-coagulation therapy).

You may not qualify if:

• Previous therapy or known intolerance/hypersensitivity with any approved or investigational mTOR inhibitor (e.g., temsirolimus, everolimus, sirolimus).
• Patients who are ≤21 days after their most recent chemotherapy and have not recovered from side effects.
• Use of an investigational drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of everolimus. For investigational drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the investigational drug and administration of everolimus is required.
• Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤28 days or limited field radiation for palliation ≤7 days for metastatic disease prior to first dose of everolimus or has not recovered from side effects of such therapy.
• Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if there is no evidence of central nervous system (CNS) disease progression, and at least 2 weeks have elapsed since treatment. Patients are not permitted to receive enzyme inducing anti-epileptic drugs (EIAEDs) during the study and should not be receiving chronic corticosteroid therapy for CNS metastases.
• Patients with known active hepatitis B (HBV) or hepatitis C (HCV) infection. Patients with risk factors for hepatitis must have HBV DNA and HCV RNA testing by PCR, and are ineligible if these tests are positive.
• Patients receiving immunization with attenuated live vaccines within 1 week of study entry or during study period.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Novartis: collaborator

Study Sites (8)

Florida Cancer Specialists-South

Fort Myers, Florida, 33916, United States

Location

Memorial Cancer Center

Hollywood, Florida, 33021, United States

Location

Woodlands Medical Specialists

Pensacola, Florida, 32503, United States

Location

Florida Cancer Specialists-East

West Palm Beach, Florida, 33401, United States

Location

Hope Cancer Center

Terre Haute, Indiana, 47802, United States

Location

Tennessee Oncology

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

Center for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Everolimus; exemestane; Tamoxifen; Fulvestrant; Anastrozole; Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Director, Regulatory Science
• Organization: Sarah Cannon Development Innovations

CANN.InnovationsMedical@sarahcannon.com

844-710-6157

Study Officials

• Denise A. Yardley, MD

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2014
• First Posted: November 17, 2014
• Study Start: December 18, 2014
• Primary Completion: January 31, 2019
• Study Completion: January 31, 2019
• Last Updated: February 17, 2020
• Results First Posted: February 17, 2020

Record last verified: 2020-02

Locations

US (8)