Clinical Trials /

Phase II Study of Everolimus Beyond Progression

NCT02269670

Description:

This phase II trial studies how well everolimus and hormone therapy work in treating patients with hormone receptor positive breast cancer that has continued to spread (progressed) or returned after a period of improvement (recurred) on everolimus and exemestane hormone therapy. Everolimus is a chemotherapy drug that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen and progesterone are hormones that can cause the growth of breast cancer cells. Hormone therapy may fight breast cancer by lowering the amount of estrogen and progesterone the body makes. Giving everolimus with a different type of hormone therapy may be an effective treatment for breast cancer in patients who progressed on everolimus with exemestane.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Study of Everolimus Beyond Progression
  • Official Title: Phase II Study of Everolimus Beyond Progression in Postmenopausal Women With Advanced, Hormone Receptor Positive Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: IRB00071229
  • SECONDARY ID: NCI-2014-02092
  • SECONDARY ID: WINSHIP2563-13
  • NCT ID: NCT02269670

Conditions

  • Estrogen Receptor-positive Breast Cancer
  • HER2-negative Breast Cancer
  • Progesterone Receptor-positive Breast Cancer
  • Recurrent Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Stage IV Breast Cancer

Interventions

DrugSynonymsArms
everolimus42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001Treatment (everolimus, hormone therapy)
anastrozoleANAS, Arimidex, ICI-D1033Treatment (everolimus, hormone therapy)
letrozoleCGS 20267, Femara, LTZTreatment (everolimus, hormone therapy)
tamoxifen citrateNolvadex, TAM, tamoxifen, TMXTreatment (everolimus, hormone therapy)
fulvestrantFaslodex, ICI 182,780Treatment (everolimus, hormone therapy)
megestrol acetateBDH 1298, Maygace, Megace, Megestil, NiagestinTreatment (everolimus, hormone therapy)

Purpose

This phase II trial studies how well everolimus and hormone therapy work in treating patients with hormone receptor positive breast cancer that has continued to spread (progressed) or returned after a period of improvement (recurred) on everolimus and exemestane hormone therapy. Everolimus is a chemotherapy drug that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen and progesterone are hormones that can cause the growth of breast cancer cells. Hormone therapy may fight breast cancer by lowering the amount of estrogen and progesterone the body makes. Giving everolimus with a different type of hormone therapy may be an effective treatment for breast cancer in patients who progressed on everolimus with exemestane.

Detailed Description

      PRIMARY OBJECTIVE:

      Progression free survival in patients with advanced or metastatic breast cancer receiving
      everolimus plus hormonal therapy beyond first progression.

      SECONDARY OBJECTIVES:

        1. Clinical benefit rate (sum of stable disease, partial response, complete response).

        2. Response rate (partial response and complete response).

        3. Overall survival.

        4. Safety, side effects and tolerability profile of everolimus.

      OUTLINE:

      Patients receive everolimus orally (PO) daily and a hormone therapy regimen chosen at the
      discretion of the investigator (anastrozole PO daily; letrozole PO daily; tamoxifen citrate
      PO daily; fulvestrant intramuscularly [IM] or PO on days 1, 15, and 29, and then monthly;
      megestrol acetate PO 4 times daily [QID]; or other regimen). Treatment continues in the
      absence of disease progression or unacceptable toxicity.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (everolimus, hormone therapy)ExperimentalPatients receive everolimus PO daily and a hormone therapy regimen chosen at the discretion of the investigator (anastrozole PO daily; letrozole PO daily; tamoxifen citrate PO daily; fulvestrant IM or PO on days 1, 15, and 29, and then monthly; megestrol acetate PO QID; or other regimen). Treatment continues in the absence of disease progression or unacceptable toxicity.
  • everolimus
  • anastrozole
  • letrozole
  • tamoxifen citrate
  • fulvestrant
  • megestrol acetate

Eligibility Criteria

        Inclusion Criteria:

          -  Estrogen (ER) and/or progesterone (PR)-positive at primary diagnosis and at metastatic
             diagnosis where tissue is available (defined as > or = 1% of staining nuclei)

          -  Progressive or recurrent breast cancer defined as disease progression or recurrence
             while on a combination of exemestane with everolimus

          -  Human epidermal growth factor receptor 2 (HER2)/neu-negative breast cancer by standard
             criteria (immunohistochemistry [IHC] < 3+ or fluorescence in situ hybridization [FISH]
             negative if IHC 2+) at primary diagnosis

          -  Histologically confirmed, measurable or evaluable disease; patients should have at
             least one measurable lesion; if applicable, Response Evaluation Criteria in Solid
             Tumors (RECIST) criteria should be used

          -  Life expectancy > 6 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

          -  Absolute neutrophil count (ANC) > 1,500/µL

          -  Platelets ≥ 100,000/µL

          -  Hemoglobin > 10 g/dL

          -  Creatinine ≤ 1.5 x upper limit of normal (ULN)

          -  Bilirubin ≤ 1.5 x ULN

          -  International normalized ratio ≤ 1.3 (or ≤ 3 on anticoagulants)

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2 x UNL unless
             related to primary disease

          -  Signed informed consent

          -  Adequate birth control

          -  Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5
             x ULN; NOTE: in case one or both of these thresholds are exceeded, the patient can
             only be included after initiation of appropriate lipid lowering medication

        Exclusion Criteria:

          -  Prior treatment with everolimus other than in combination with hormonal therapy for
             treatment of breast cancer or prior treatment with another mammalian target of
             rapamycin (mTOR) inhibitor (sirolimus, temsirolimus) for any indication

          -  HER2 positive disease as defined by 3+ IHC or positive FISH (both in primary and
             metastatic sites)

          -  Active infection: temperature > 100 Fahrenheit (F), fever of unknown origin, active
             symptoms or signs of infection as defined by the investigator

          -  Uncontrolled central nervous system metastases

          -  Life-threatening, visceral metastases

          -  Pregnant or lactating women

          -  Prior chemotherapy within the last 4 weeks

          -  Prior radiation therapy within the last 4 weeks; prior radiation therapy to indicator
             lesion (unless objective disease recurrence or progression within the radiation portal
             has been documented since completion of radiation)

          -  Concomitant malignancies or previous malignancies within the last 5 years, with the
             exception of adequately treated basal or squamous cell carcinoma of the skin or
             carcinoma in situ of the cervix

          -  History of significant cardiac disease, cardiac risk factors or uncontrolled
             arrhythmias

          -  Hypersensitivity to trial medications (everolimus)

          -  Emotional limitations, which the investigator judges could limit the patient's ability
             to follow up and comply with study procedures

          -  Patients receiving chronic, systemic treatment with corticosteroids or another
             immunosuppressive agent

          -  Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN

          -  Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent
             hepatitis

          -  A known history of human immunodeficiency virus (HIV) seropositivity

          -  Impairment of gastrointestinal function or gastrointestinal disease that may
             significantly alter the absorption of EVEROLIMUS (e.g., ulcerative disease,
             uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel
             resection)

          -  Patients with an active, bleeding diathesis

          -  Female patients who are pregnant or breast feeding, or adults of reproductive
             potential who are not using effective birth control methods; if barrier contraceptives
             are being used, these must be continued throughout the trial by both sexes; hormonal
             contraceptives are not acceptable as a sole method of contraception; (women of
             childbearing potential must have a negative urine or serum pregnancy test within 7
             days prior to administration of EVEROLIMUS)

          -  Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs,
             resulting in dyspnea at rest

          -  Taking any of the following agents:

               -  Chronic treatment with systemic steroids or another immunosuppressive agent (use
                  of steroids as part of management of everolimus toxicities will be allowed)

               -  Live vaccines

               -  Patients who have received live attenuated vaccines within 1 week of start of
                  everolimus and during the study; patient should also avoid close contact with
                  others who have received live attenuated vaccines; examples of live attenuated
                  vaccines include intranasal influenza, measles, mumps, rubella, oral polio,
                  bacillus Calmette-Guérin (BCG), yellow fever, varicella and TY21a typhoid
                  vaccines

               -  Drugs or substances known to be inhibitors or inducers of the isoenzyme
                  cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate (partial response plus complete response) using RECIST
Time Frame:Up to 2 years
Safety Issue:
Description:Measured at different time points, e.g. 8, 16, and 24 weeks, and will be summarized as percentage of stable disease, complete remission or partial remission along with 95% confidence interval.

Secondary Outcome Measures

Measure:Clinical benefit rate (response rate plus stable disease)
Time Frame:Up to 2 years
Safety Issue:
Description:Measured at different time points and summarized as a percentage along with 95% confidence interval.
Measure:Overall survival (OS)
Time Frame:From the initiation of alternate hormonal treatment in combination with everolimus to time of death from any cause, assessed up to 2 years
Safety Issue:
Description:The median OS and survival rate at different time points for this study will be estimated by Kaplan-Meier method along with 95% confidence interval.
Measure:Incidence of adverse events assessed using Common Terminology Criteria for Adverse Events version 4.0
Time Frame:Up to 2 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Emory University

Last Updated

September 29, 2017