Clinical Trials /

NECTAR Everolimus Plus Cisplatin in Triple (-) Breast Cancer

NCT01931163

Description:

RATIONALE: Everolimus plus Cisplatin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: The purpose of this study is to test how effective combining Cisplatin chemotherapy with Everolimus is in treating subjects with triple negative breast cancer who have residual disease after chemotherapy.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

NECTAR <span class="go-doc-concept go-doc-intervention">Everolimus</span> Plus <span class="go-doc-concept go-doc-intervention">Cisplatin</span> in Triple (-) <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: NECTAR Everolimus Plus Cisplatin in Triple (-) Breast Cancer
  • Official Title: Neoadjuvant Phase II Study Of Everolimus Plus Cisplatin In Triple Negative Breast Cancer Patients With Residual Disease After Standard Chemotherapy
  • Clinical Trial IDs

    NCT ID: NCT01931163

    ORG ID: CRAD001 JUST213

    NCI ID: 0513-0062

    Trial Conditions

    Breast Cancer

    Triple Negative Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Everolimus RAD001, Afinitor Everolimus

    Trial Purpose

    RATIONALE: Everolimus plus Cisplatin may stop the growth of tumor cells by blocking some of
    the enzymes needed for cell growth and by blocking blood flow to the tumor.

    PURPOSE: The purpose of this study is to test how effective combing a Cisplatin
    chemotherapy with Everolimus is in treating subjects with residual triple negative breast
    cancer, who have already received chemotherapy prior to surgery.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Everolimus Experimental Cisplatin 20 mg/m2 IV infusion over 60 minutes, weekly (Days 1, 8, 15) x 4 cycles Everolimus 10mg by mouth daily Everolimus

    Eligibility Criteria

    Inclusion Criteria:

    1. Female patients 18 years of age.

    2. Clinical/pathological documentation of residual disease after neo-adjuvant therapy.

    3. Patients with synchronous bilateral cancers are eligible only if:

    Index cancer is triple-negative, defined as ER-, PR-, and HER2-.

    4. HER2 negative tumors. HER2 negativity must be confirmed by one of the following:

    - FISH-negative (FISH ratio <2.2), or

    - IHC 0-1+, or

    - IHC 2-3+ AND FISH-negative (FISH ratio <2.2).

    5. Estrogen receptor negative and progesterone receptor negative (<10% staining by IHC
    for estrogen receptor and progesterone receptor).

    6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

    7. Adequate hematologic function, defined by:

    - Absolute neutrophil count 2 >1000/mm3

    - Platelet count 100,000/mm3

    - Hemoglobin >9 g/dL

    8. Adequate liver function, defined by:

    - AST and ALT 2.5 x the upper limit of normal (ULN)

    - Total bilirubin 1.5 x ULN (unless the patient has grade 1 bilirubin elevation
    due to Gilbert's disease or a similar syndrome involving slow conjugation of
    bilirubin).

    9. Adequate renal function, defined by:

    Serum creatinine 1.5 x ULN

    10. Complete staging work-up 24 weeks prior to initiation of study treatment with
    computed tomography (CT) scans of the chest and abdomen/pelvis (abdomen/pelvis
    preferred; abdomen accepted), a CT scan of the head or MRI of the brain (if
    symptomatic), and either a positron emission tomography (PET) scan or a bone scan.

    11. Adequate cardiac function, defined by a left ventricular ejection fraction (LVEF)
    value of >50% (or normal per institutional guidelines) by MUGA scan or echocardiogram
    (ECHO).

    12. Patients with previous history of invasive cancers (including breast cancer) are
    eligible if definitive treatment was completed more than 5 years prior to initiating
    current study treatment, and there is no evidence of recurrent disease.

    13. Women of childbearing potential must have a negative serum or urine pregnancy test
    performed within 7 days prior to start of treatment. If a woman becomes pregnant or
    suspects she is pregnant while participating in this study, she must agree to inform
    her treating physician immediately.

    14. Patient must be accessible for treatment and follow-up.

    15. Women of childbearing potential must agree to use an acceptable method of birth
    control to avoid pregnancy for the duration of study treatment, and for 3 months
    thereafter.

    16. Able to swallow and retain oral medication.

    17. Patient must be willing to undergo breast biopsies as required by the study protocol.

    18. All patients must be able to understand the investigational nature of the study and
    give written informed consent prior to study entry.

    Exclusion Criteria:

    1. Women who are pregnant or breastfeeding.

    2. History of previously treated ductal carcinoma in situ (DCIS) is acceptable.

    3. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
    resection of the stomach or small bowel.

    4. Known intolerance or hypersensitivity to Everolimus or other rapamycin analogs (e.g.
    sirolimus, temsirolimus);

    5. Previous cancer (with the exception of non-melanoma skin cancer or cervical carcinoma
    in situ) in the past 5 years.

    6. Patients who have any severe and/or uncontrolled medical conditions such as:

    1. unstable angina pectoris, symptomatic congestive heart failure, myocardial
    infarction 6 months prior to start of Everolimus, serious uncontrolled cardiac
    arrhythmia, or any other clinically significant cardiac disease

    2. Symptomatic congestive heart failure of New York heart Association Class III or
    IV

    3. active (acute or chronic) or uncontrolled severe infection, liver disease such
    as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e.
    quantifiable HBV-DNA and/or positive HbsAg, quantifiable HCV-RNA),

    4. known severely impaired lung function (spirometry and DLCO 50% or less of normal
    and O2 saturation 88% or less at rest on room air),

    5. active, bleeding diathesis;

    7. Patients may not receive any other investigational or anti-cancer treatments while
    participating in this study.

    8. Concurrent severe, uncontrolled infection or intercurrent illness including, but not
    limited to, ongoing or active infection, or psychiatric illness/social situations
    that would limit compliance with study requirements.

    9. Mental condition that would prevent patient comprehension of the nature of, and risk
    associated with, the study.

    10. Inability to comply with study and/or follow-up procedures.

    11. 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, BCG, yellow fever, varicella and TY21a typhoid vaccines;

    12. Known history of HIV seropositivity;

    13. Women of child-bearing potential (WOCBP), defined as all women physiologically
    capable of becoming pregnant, unless they are using highly effective methods of
    contraception during dosing of study treatment. Highly effective contraception
    methods include combination of any two of the following (a+b or a+c or b+c):

    1. Use of oral, injected or implanted hormonal methods of contraception or;

    2. Placement of an intrauterine device (IUD) or intrauterine system (IUS);

    3. Barrier methods of contraception: condom or occlusive cap (diaphragm or
    cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository;

    4. Total abstinence or;

    5. Male/female sterilization. Women are considered post-menopausal and not of
    child-bearing potential if they have had 12 months of natural (spontaneous)
    amenorrhea with an appropriate clinical profile (e.g. age appropriate, history
    of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or
    without hysterectomy) or tubal ligation at least six weeks prior to treatment.
    In the case of oophorectomy alone, only when the reproductive status of the
    woman has been confirmed by follow up hormone level assessment is she considered
    not of child-bearing potential.

    14. Chronic treatment with corticosteroids or other immunosuppressive agents. Topical or
    inhaled corticosteroids are allowed;

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    tumor response

    Secondary Outcome Measures

    Trial Keywords