Everolimus Combined With Anti-estrogen Therapy in Hormone-Receptor-Positive HER-2 Negative Advanced Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Everolimus; Exemestane; Tamoxifen; Fulvestrant; Anastrozole; Letrozole; Toremifine
Intervention description: Anti-estrogen therapy; Anti-estrogen therapy; Anti-estrogen therapy; Anti-estrogen therapy; Anti-estrogen therapy; Anti-estrogen therapy
Intervention MeSH terms: Tamoxifen; Everolimus; Letrozole; Fulvestrant; Anastrozole; Exemestane
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ER-Positive Breast Cancer; HER2-Negative Breast Cancer; everolimus; anti-estrogen therapy; PR-Positive Breast Cancer; Afinitor

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologic diagnosis of unresectable, locally recurrent or MBC.

          2. ER and/or PR-positive tumors with staining by immunohistochemistry (IHC) based on the
             most recent biopsy.

          3. 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.

          4. 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.

          5. 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.

          6. 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).

          7. 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.

          8. Adequate hematologic, hepatic and renal function.

          9. 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).

         10. Age ≥ 18 years.

         11. ECOG Performance Status score of 0-2.

         12. Life expectancy of ≥ 12 weeks.

        Exclusion Criteria:

          1. Previous therapy or known intolerance/hypersensitivity with any approved or
             investigational mTOR inhibitor (e.g., temsirolimus, everolimus, sirolimus).

          2. Patients who are ≤21 days after their most recent chemotherapy and have not recovered
             from side effects.

          3. 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.

          4. 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.

          5. 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.

          6. 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.

          7. Patients receiving immunization with attenuated live vaccines within 1 week of study
             entry or during study period.

        NOTE: There are additional inclusion/exclusion criteria. The study center will determine
        patient eligibility and respond to any questions.