Clinical Trials /

Neoadj ph 2 AI Plus Everolimus in Postmenopausal Women w/ ER Pos/HER2 Neg, Low Risk Score

NCT02236572

Description:

The purpose of this study is to see whether adding everolimus to hormone treatment before breast surgery will increase the chances of shrinking the breast cancer in those patients with hormone-responsive breast cancer and a lower Oncotype DX® Recurrence Score ( 25 or less), compared to prior experience with hormone therapy alone. Everolimus is a drug currently approved for use by the United States Food and Drug administration (FDA) for the treatment of patients with advanced or metastatic kidney or breast cancer. Everolimus is considered investigational for non-metastatic breast cancer patients.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neoadj ph 2 AI Plus Everolimus in Postmenopausal Women w/ ER Pos/HER2 Neg, Low Risk Score
  • Official Title: A Neoadjuvant Phase II Trial of Aromatase Inhibitors in Combination With Everolimus in Postmenopausal Women With Hormone Receptor Positive/HER2 Negative Breast Cancers With Low and Intermediate Risk (< 25) Oncotype Dx Recurrence Scores

Clinical Trial IDs

  • ORG STUDY ID: 1405013982
  • NCT ID: NCT02236572

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
EverolimusAromatase Inhibitor plus Everolimus

Purpose

The purpose of this study is to see whether adding everolimus to hormone treatment before breast surgery will increase the chances of shrinking the breast cancer in those patients with hormone-responsive breast cancer and a lower Oncotype DX® Recurrence Score ( 25 or less), compared to prior experience with hormone therapy alone. Everolimus is a drug currently approved for use by the United States Food and Drug administration (FDA) for the treatment of patients with advanced or metastatic kidney or breast cancer. Everolimus is considered investigational for non-metastatic breast cancer patients.

Detailed Description

      This is a single arm open-labeled neoadjuvant phase II clinical trial evaluating everolimus
      in combination with an aromatase inhibitor in postmenopausal women with hormone receptor
      positive/HER2 negative breast cancers with low and intermediate risk (< 25) Recurrence Scores
      by Oncotype Dx.
    

Trial Arms

NameTypeDescriptionInterventions
Aromatase Inhibitor plus EverolimusExperimentalAromatase inhibitor plus everolimus by mouth daily for 26 weeks
  • Everolimus

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have a histologically confirmed diagnosis of hormone receptor positive,
             HER2 negative invasive breast carcinoma.

          -  Tumors must be estrogen and/or progesterone receptor positive according to ASCO/CAP
             2010 guidelines as either ER or PR ≥ 1% positive nuclear staining by
             immunohistochemistry. Estrogen and/or progesterone receptor results by Oncotype Dx
             will not be accepted.

          -  Tumors must be HER2 negative as defined according to ASCO/CAP 2013, as HER2 0 - 1+ by
             IHC or non-amplified FISH or CISH. If HER2 IHC is 2+, FISH/CISH must be performed and
             must not be positive (must be a ratio of < 2), but otherwise FISH/CISH is not required
             if IHC is 0 or 1+ by institutional standards.

          -  Patients must not have had prior ipsilateral breast-conserving surgery or total
             mastectomy and be eligible for neoadjuvant treatment.

          -  Clinical Stage II-IIIC (T2-4 N0-3 M0) by mammogram, ultrasound or MRI

          -  Baseline Oncotpye Dx recurrence score < 25.

          -  Staging studies with a CT scan of the chest and abdomen and bone scan, or a PET/CT is
             required for clinical stage III, and are considered optional for stage II breast
             cancers.

          -  Patients with multifocal, multicentric and synchronous bilateral breast cancers are
             allowed:

               -  Multifocal disease is defined as more than one invasive cancer < 2 cm from the
                  largest lesion within the same breast quadrant.

               -  Multicentric disease is defined as more than one invasive cancer ≥ 2 cm from the
                  largest lesion within the same breast quadrant or more than one lesion in
                  different quadrants.

               -  Synchronous bilateral disease is defined as invasive breast cancer in both
                  breasts, diagnosed within 30 days of each other.

               -  In patients with multicentric or bilateral invasive breast cancers, all sampled
                  lesions must be hormone receptor-positive and HER2-negative. Any lesion measuring
                  > 1 cm must have an Oncotype Dx and the score must be < 25. Lesions less than 1
                  cm in size are not required to have an Oncotype Dx. One lesion (typically the
                  largest) should be designated as the target lesion for which clinical and
                  radiographic response to the neoadjuvant therapy will be judged.

               -  Patients with a hormone receptor-positive, HER2-negative invasive cancer that
                  meets study criteria may have ductal carcinoma in situ in another quadrant of the
                  same breast or in the contralateral breast even if the DCIS is hormone
                  receptor-negative.

          -  Patients must have adequate bone marrow function, as defined by peripheral granulocyte
             count of ≥ 1,500/mL, hemoglobin ≥ 9 g/dL and a platelet count ≥ 100,000/ mL within 28
             days prior to registration.

          -  Patients must have adequate hepatic function obtained within 28 days prior to
             registration and documented by all of the following:

               -  Bilirubin ≤ 1.5 mg/dL (or ≤ 3.0 mg/dL if due to Gilbert's Syndrome)

               -  ALT and AST ≤ 1.5 x Institutional Upper Limit of Normal (IULN)

               -  Alkaline phosphatase ≤ 1.5 x IULN

          -  Patients must have adequate renal function with serum creatinine level ≤ IULN within
             28 days prior to registration.

          -  Patients must have a fasting cholesterol ≤ 300 mg/dl OR ≤7.75 mmol/L and triglycerides
             ≤ 2.5 x IULN obtained within 28 days prior to registration. Patients may be on lipid
             lowering agents to reach these values.

          -  Patients must have a ECOG performance status of 0-2.

          -  Patients must be able to take oral medications.

          -  Postmenopausal women (women are considered post-menopausal and not of child-bearing
             potential if they are > 18 years of age and have had 12 months of natural
             (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate,
             history of vasomotor symptoms or biochemically postmenopausal by estradiol and FSH
             levels) prior to enrollment, or have had surgical bilateral oophorectomy (with or
             without hysterectomy) prior to registration. Medical ovarian suppression with LHRH
             agonists to render a patient postmenopausal will not be acceptable.

             16. Patients or their legally authorized representative must be informed of the
             investigational nature of this study and must sign and give written informed consent
             prior to any screening procedures in accordance with institutional and federal
             guidelines.

        Exclusion Criteria:

          -  Patients must not have inflammatory breast cancer (T4d) and must not have metastatic
             breast cancer (Stage IV disease).

          -  Patients must not have prior exposure to mTOR inhibitors (e.g. rapamycin, everolimus,
             sirolimus, temsirolimus, deforolimus).

          -  Patients must not have prior treatment with any investigational drug within the
             preceding 28 days and must not be planning to receive any other investigational drug
             for the duration of the study.

          -  Patient may not have any impairment of gastrointestinal function or gastrointestinal
             disease that may significantly alter the absorption of the drug (e.g. ulcerative
             disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small
             bowel resection).

          -  Uncontrolled diabetes mellitus as defined by HbA1c >8% within 28 days prior to
             registration despite adequate therapy.

          -  Patients who have any severe and/or uncontrolled cardiac disease within ≤ 6 months
             prior to start of everolimus, including: unstable angina pectoris, Symptomatic
             congestive heart failure of New York heart Association Class III or IV, myocardial
             infarction, serious uncontrolled cardiac arrhythmia, or any other clinically
             significant cardiac disease

          -  Patients must not have an organ allograft or other history of immune compromise.

          -  Patients must not be receiving chronic, systemic treatment with corticosteroids or
             other immunosuppressive agent. Topical or inhaled corticosteroids are allowed.

          -  Patients must not have a known history of HIV seropositivity

          -  Patients must not have a known diagnosis of hepatitis B or C. Patients with the
             following risk factors must have hepatitis screening pre-treatment:

               -  Blood transfusions prior to 1990

               -  Current or prior IV drug users

               -  Current or prior dialysis

               -  Household contact with a hepatitis B or C patient

               -  Current or prior high-risk sexual activity

               -  History of jaundice.

          -  Patients must not have any known uncontrolled underlying pulmonary disease or severely
             impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation
             88% or less at rest on room air),

          -  Active (acute or chronic) or uncontrolled severe infection.

          -  Patients who have received live attenuated vaccines within 1 week of start of
             Everolimus, or have plans to receive such vaccination while on protocol treatment.
             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, BCG, yellow fever, varicella and TY21a typhoid vaccines;

          -  Patients who are currently part of or have participated in any clinical investigation
             with an investigational drug within 1 month prior to dosing;

          -  Patients must not have taken within 14 days prior to registration , be taking, nor
             plan to take while on protocol treatment, strong CYP3A4 inhibitors, and/or CYP3A4
             inducers.

          -  Patients with active bleeding diathesis.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Achievement of a PEPI score of 0 following neoadjuvant treatment with everolimus and an aromatase inhibitor
Time Frame:up to 26 weeks
Safety Issue:
Description:(PEPI) preoperative endocrine prognostic index. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and estrogen receptor status of the surgical specimen. An HR in the range of 1-2 receives one risk point; a HR in the 2-2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each patient is the sum of all the risk points accumulated from the four factors in the model.

Secondary Outcome Measures

Measure:Participant ability to tolerate study treatment with minimal side effects
Time Frame:assessed up to 30 days after completion of study treatment
Safety Issue:
Description:Adverse events that begin or worsen after informed consent will be recorded. Adverse event monitoring should be continued for at least 30 days following the last dose of treatment.

Details

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

Trial Keywords

  • Postmenopausal
  • ER-positive, PR-positive, HER2-negative
  • Low and intermediate risk

Last Updated

March 6, 2017