Clinical Trials /

Phase II Short-term Adjuvant Therapy and Biomarker Studies With Targeted Agents in Women With Estrogen Receptor Negative Breast Cancer

NCT01471106

Description:

The goal of this clinical research study is to learn if dasatinib can help prevent breast cancer from developing in the unaffected breast. Dasatinib is designed to decrease the activity of one or more proteins that are responsible for the uncontrolled growth of tumor cells. This is an investigational study. Dasatinib is FDA approved and commercially available for the treatment of leukemia. Its use in breast cancer patients in investigational. Up to 66 patients will take part in this multicenter study. Up to 60 will be enrolled at MD Anderson.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Phase II Short-term Adjuvant Therapy and Biomarker Studies With Targeted Agents in Women With Estrogen Receptor Negative <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: Phase II Short-term Adjuvant Therapy and Biomarker Studies With Targeted Agents in Women With Estrogen Receptor Negative Breast Cancer
  • Official Title: Phase II Short-term Adjuvant Therapy and Biomarker Studies With Targeted Agents in Women With Estrogen Receptor Negative Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT01471106

    ORG ID: 2010-0794

    NCI ID: NCI-2012-00037

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Dasatinib BMS-354825, Sprycel Group 1: Dasatinib 40 mg, Group 2: Dasatinib 80 mg

    Trial Purpose

    The goal of this clinical research study is to learn if dasatinib can help prevent breast
    cancer from developing in the unaffected breast.

    Dasatinib is designed to decrease the activity of one or more proteins that are responsible
    for the uncontrolled growth of tumor cells.

    Detailed Description

    Study Drug Administration:

    If you are found to be eligible to take part in this study, you will be randomly assigned
    (as in the flip of a coin) to 1 of 3 study groups:

    - If you are in Group 1, you will take dasatinib 40mg once a day by mouth with water.

    - If you are in Group 2, you will take dasatinib 80mg once a day by mouth with water.

    - If you are in Group 3, you will not receive dasatinib.

    You will be given a study drug diary to complete. In the diary, you will record when you
    take the study drug.

    Study Visits:

    At Month 1:

    - Blood (about 2 tablespoons) will be drawn for routine tests.

    - You will be asked about any drugs you may be taking and side effects you may be having.

    - Your drug diary will be reviewed.

    At Month 2 you will be called by a nurse and asked about any drugs you are taking and side
    effects you may be having. You will also be asked to review your drug diary. This call will
    take about 20 minutes

    At Month 3 (or if you leave the study early):

    - You will have a fine needle aspirate (FNA) of the breast for biomarker testing.
    Biomarkers are found in the blood/tissue and may be related to your reaction to the
    study drug.

    - Blood (about 2-3 tablespoons) will be drawn for biomarker testing.

    - You will be asked about any drugs you may be taking and side effects you may be having.

    - Your drug diary will be reviewed.

    Length of Study:

    You may remain on study for up to 3 months. You will no longer be able to take the study
    drug if the disease gets worse, if intolerable side effects occur, or if you are unable to
    follow study directions.

    This is an investigational study. Dasatinib is FDA approved and commercially available for
    the treatment of leukemia. Its use in breast cancer patients in investigational.

    Up to 66 patients will take part in this multicenter study. Up to 60 will be enrolled at MD
    Anderson.

    Trial Arms

    Name Type Description Interventions
    Group 1: Dasatinib 40 mg Experimental Dasatinib 40 mg by mouth once a day for 3 months (+/- 7 days), At the end of the 3 months (+/- 7 days) participants undergo a repeat FNA and blood collection for the same marker analyses. Dasatinib
    Group 3: No Dasatinib No Intervention No treatment control group. At the end of the 3 months (+/- 7 days) participants undergo a repeat FNA and blood collection for the same marker analyses.
    Group 2: Dasatinib 80 mg Experimental Dasatinib 80 mg by mouth once a day for 3 months (+/- 7 days). At the end of the 3 months (+/- 7 days) participants undergo a repeat FNA and blood collection for the same marker analyses. Dasatinib

    Eligibility Criteria

    Inclusion Criteria:

    1. Histological confirmation of ER negative breast carcinoma, stage I, II, or III

    2. Completed all adjuvant therapy including (if indicated) endocrine, trastuzumab,
    radiation therapy

    3. At least 18 years of age.

    4. Female: A female is eligible to enter and participate in the study if she is of: a.
    Non-childbearing potential (i.e., women with functioning ovaries who have a current
    documented tubal ligation or hysterectomy, or women who are post-menopausal); or b.
    Childbearing potential (i.e., women with functioning ovaries and no documented
    impairment of oviductal or uterine function that would cause sterility. This category
    includes women with oligomenorrhoea (severe), women who are perimenopausal, and young
    women who have begun to menstruate), has a negative serum pregnancy test at
    screening, and agrees to one of the following where considered acceptable to the
    local IRB/IEC: Double-barrier contraception (condom with spermicidal jelly, foam
    suppository, or film; diaphragm with spermicide; or male condom and diaphragm).
    Abstinence from sexual intercourse from 2 weeks prior to administration of the
    investigational product, throughout the active study treatment period.

    5. (Continued from above) Male partner who is sterile prior to the female subject's
    entry into the study and is the sole sexual partner for that female subject. Any
    intrauterine device (IUD). Barrier methods including diaphragm or condom with a
    spermicide.

    6. Able to swallow and retain oral medication.

    7. ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2.

    8. Provided written informed consent.

    9. Adequate bone marrow function: Hemoglobin >/= 9 gm/dL. Absolute granulocyte count
    >/= 1,500/mm^3 (1.5 x 10^9/L). Platelets >/= 75,000/mm^3 (100 x 10^9/L).

    10. Serum creatinine < 1.4 mg/dL or calculated creatinine clearance (CrCl) >/= 30 mL/min

    11. Total bilirubin </= 1.5 times the upper limit of the reference range

    12. Aspartate and alanine transaminase (AST or ALT) </= 2 times the upper limit of the
    reference range.

    13. Patients must have a baseline ECG with QTcF within the normal range within 28 days
    prior to registration.

    14. Normal mammogram of unaffected breast within 12 months prior to study entry.

    Exclusion Criteria:

    1. Unwillingness to undergo RPFNA.

    2. Contraindication to RPFNA including breast implant(s), bilateral radiation,
    anticoagulation.

    3. Concurrent medical condition that would increase drug toxicity: Pleural or
    pericardial effusion, coagulation or platelet function disorder, ongoing or recent
    (less than 3 months gastrointestinal bleeding)

    4. Uncontrolled angina, congestive heart failure, MI (within last 6 months), congenital
    long QT syndrome, history of clinically significant ventricular arrhythmia, prolonged
    QTcF interval on pre-entry EKG (greater than normal range)

    5. Hypokalemia or hypomagnesemia if it cannot be corrected

    6. Is a pregnant or lactating female.

    7. Has evidence of recurrent or metastatic (Stage IV) breast cancer.

    8. Is considered medically unfit for the study by the investigator as a result of the
    medical interview, physical exam, or screening investigations.

    9. Has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to
    dasatinib

    10. Has received treatment with any investigational drug in the previous 4 weeks.

    11. Has received chemotherapy, immunotherapy, biologic therapy or endocrine therapy
    within the past 12 weeks.

    12. Is currently receiving oral steroid treatment (inhaled steroids are permitted)

    13. Oral estrogen, progesterone, testosterone therapy within last 3 months.

    14. Concomitant Medications, consider the following prohibitions (Drugs must be
    discontinued for 7 days prior to starting protocol therapy): Drugs that are generally
    accepted to have a risk of causing Torsades de Pointes including : quinidine,
    procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide erythromycins,
    clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide,
    cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone,
    halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine. The concomitant
    use of H2 blockers or proton pump inhibitors with dasatinib is not recommended. The
    use of antacids should be considered in place of H2 blockers or proton pump
    inhibitors in patients receiving dasatinib therapy. Patient agrees to discontinue St.
    John's Wort while receiving dasatinib therapy

    15. Patient may not be receiving any prohibited CYP3A4 inhibitors

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Change in Ki-67 in Breast Tissue of High-Risk Women

    Secondary Outcome Measures

    Trial Keywords

    Breast Cancer

    Estrogen Receptor Negative Breast Cancer

    Biomarker studies

    Ki-67

    Dasatinib

    BMS-354825

    Sprycel