Clinical Trials /

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

NCT02291913

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Everolimus Combined With Anti-estrogen Therapy in Hormone-Receptor-Positive HER-2 Negative Advanced Breast Cancer
  • Official Title: Phase II Open Label Study of Everolimus in Combination With Anti-estrogen Therapy in Hormone Receptor-Positive HER2-Negative Advanced Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: SCRI BRE 212
  • NCT ID: NCT02291913

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
EverolimusAfinitoreverolimus
Exemestaneeverolimus
Tamoxifeneverolimus
Fulvestranteverolimus
Anastrozoleeverolimus
Letrozoleeverolimus
Toremifineeverolimus

Purpose

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.

Detailed Description

      This is a multi-centered, open-labeled, Phase II study on metastastic breast cancer (MBC).
      The patient population includes locally recurrent or MBC patients with cytologically or
      histologically confirmed hormone receptor-positive breast cancer who have demonstrated
      disease progression on prior anti-estrogen therapy or therapies. Investigators propose to
      evaluate the efficacy of Everolimus in patients with ER-positive (estrogen receptor-positive)
      metastatic breast cancer who have progressed on anti-estrogen therapy. Forty-six (46)
      patients are planned for enrollment in the trial.
    

Trial Arms

NameTypeDescriptionInterventions
everolimusExperimentalEverolimus 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.
  • Everolimus
  • Exemestane
  • Tamoxifen
  • Fulvestrant
  • Anastrozole
  • Letrozole
  • Toremifine

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:up to 3 years
Safety Issue:
Description:All patients who received at least 1 cycle of study treatment and had at least 1 post-baseline assessment will be evaluable. PFS defined as the time from Day 1 of study drug administration to disease progression as defined by RECIST (Response Evaluation Criteria in Solid Tumors) v1.1 criteria, or death on study.

Secondary Outcome Measures

Measure:Number of patients with Adverse Events (AEs) as a Measure of Safety and Tolerability
Time Frame:approximately 1 year from first treatment
Safety Issue:
Description:Assessments will be made through analysis of the reported incidence of treatment-emergent AEs.
Measure:Overall Response Rate (ORR)
Time Frame:every 8 weeks until discontinuation, estimated 1 year from first treatment
Safety Issue:
Description:The proportion of patients with observed complete response (CR) or partial response (PR) according to RECIST v1.1 criteria.
Measure:Clinical Benefit Rate (CBR)
Time Frame:approximately 1 year from first treatment
Safety Issue:
Description:The proportion of patients with CR + PR + Stable Disease (SD) x 6 months
Measure:Duration of Response (DOR)
Time Frame:every 8 weeks until discontinuation, estimated 1 year from first treatment
Safety Issue:
Description:Defined as time from first date of response (CR or PR) to disease progression or death as defined by RECIST v1.1 criteria.
Measure:Overall Survival
Time Frame:up to 3 years from first treatment
Safety Issue:
Description:Defined as from Day 1 of study drug administration to date of death due to any cause.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:SCRI Development Innovations, LLC

Trial Keywords

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

Last Updated

January 31, 2018