Clinical Trials /

Phase II Trial of EVEROLIMUS ± Trastuzumab in Hormone-Refractory Metastatic Breast Cancer

NCT00912340

Description:

This phase II trial studies how well everolimus with or without trastuzumab works in treating patients with breast cancer that has not responded to hormone therapy and has spread from where it started to other places in the body. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. Giving everolimus and adding trastuzumab at the time of disease progression may be an effective treatment for breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Trial of EVEROLIMUS ± Trastuzumab in Hormone-Refractory Metastatic Breast Cancer
  • Official Title: Phase II Trial of EVEROLIMUS ± Trastuzumab in Hormone-Refractory Metastatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: IRB00012495
  • SECONDARY ID: WCI1524-08
  • NCT ID: NCT00912340

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
EverolimusAfinitor, RAD001Everolimus, trastuzumab
TrastuzumabHerceptinEverolimus, trastuzumab

Purpose

This phase II trial studies how well everolimus with or without trastuzumab works in treating patients with breast cancer that has not responded to hormone therapy and has spread from where it started to other places in the body. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. Giving everolimus and adding trastuzumab at the time of disease progression may be an effective treatment for breast cancer.

Detailed Description

      Breast cancer is the most common type of invasive cancer in women, with more than 1 million
      cases and almost 600,000 deaths occurring worldwide annually. Breast cancer that has spread
      to other parts of the body (metastasized) is usually not curable. Patients with a type of
      metastatic breast cancer that has hormone receptors on the surface of the cancer cells are
      usually treated with the drug tamoxifen, which interferes with the function of these hormone
      receptors. However, the average survival time for these patients remains at around 36 months.

      In patients who no longer respond to tamoxifen (hormone-refractory breast cancer), the cancer
      drug trastuzumab (Herceptin), which acts on a protein called human epidermal growth factor
      receptor 2 (HER2), may have some activity. In addition, studies suggest that the drug
      everolimus, which acts on a pathway within cancer cells that is important for growth of the
      tumor, may make the cancer cells more sensitive to treatment with trastuzumab. Thus, the two
      drugs may act together to increase their anti-cancer potential.
    

Trial Arms

NameTypeDescriptionInterventions
Everolimus, trastuzumabExperimentalPatients receive 10 mg everolimus PO daily and continue to receive their most recent hormone therapy. Patients achieving disease progression receive 8 mg/kg trastuzumab IV over 30-90 minutes once every 3 weeks in combination with everolimus and hormone therapy.
  • Everolimus

Eligibility Criteria

        Inclusion Criteria:

        Patients will be included in the study based on the following criteria:

          -  Hormone-refractory metastatic breast cancer defined as disease progression within 6
             months from starting most recent hormonal therapy

          -  At least one line of endocrine therapy in the metastatic setting

          -  Candidate for hormonal therapy (ER and/or progestin receptor [PR]-positive at primary
             diagnosis and at metastatic diagnosis where tissue is available)

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

          -  Must have a biopsy in the metastatic setting with HER2 expression of 1+ or 2+ by IHC

          -  If biopsy of metastatic lesion is performed prior to study entry, HER2 expression by
             IHC must be 1+ or 2+

          -  Histologically confirmed, measurable or evaluable disease; if disease is measurable,
             Response Evaluation Criteria In Solid Tumors (RECIST) criteria should be used

          -  Life expectancy > 6 months

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

          -  Adequate bone marrow function as indicated by the following:

               -  Absolute neutrophil count (ANC) > 1500/µL

               -  Platelets ≥ 100,000/µL

               -  Hemoglobin > 10 g/dL

          -  Adequate renal function, as indicated by creatinine ≤ 1.5x upper limit of normal (ULN)

          -  Adequate liver function, as indicated by bilirubin ≤ 1.5x ULN

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

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2x ULN 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:

        Patients will be excluded from the study based on the following criteria:

          -  Prior treatment with trastuzumab or other HER2-directed therapies or with an mammalian
             target of rapamycin (mTOR) inhibitor within 12 months of study entry (when cancer was
             not definitely hormone refractory)

          -  HER2 0 or 3+ by IHC on pre-treatment biopsy of metastatic lesion (if performed)

          -  Active infection

          -  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

          -  Ejection fraction < 50% or below the lower limit of the institutional normal range,
             whichever is lower

          -  Hypersensitivity to trial medications

          -  Emotional limitations

          -  Prior treatment with any investigational drug within the preceding 4 weeks

          -  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 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)

          -  Patients who have received prior treatment with an mTOR inhibitor (sirolimus,
             temsirolimus, 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

               -  Live vaccines

               -  Drugs or substances known to be inhibitors or inducers of the isoenzyme
                  cytochrome P450, family 3, subfamily A (CYP3A)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate
Time Frame:Every 6 to 12 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Clinical benefit, progression-free survival
Time Frame:Every 6 to 12 weeks
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Emory University

Trial Keywords

  • Breast Cancer

Last Updated

December 1, 2017