Clinical Trials /

Talazoparib Before Standard Therapy in Treating Patients With Invasive, BRCA-Mutated Breast Cancer

NCT02282345

Description:

This phase II trial studies the side effects of talazoparib when given before standard therapy in treating patients with breast cancer that has spread to nearby healthy tissue and has a mutation in a breast cancer, early onset (BRCA) gene. Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth, and may be especially effective in patients with BRCA mutations. It is not yet known whether adding talazoparib before standard treatment is safe in treating patients with BRCA mutated breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Neoadjuvant BMN673 for Patients With a BRCA Deleterious <span class="go-doc-concept go-doc-keyword">Mutation</span>

Title

  • Brief Title: Neoadjuvant BMN673 for Patients With a BRCA Deleterious Mutation
  • Official Title: A Pilot Study of BMN673 as a Neoadjuvant Study in Patients With a Diagnosis of Invasive Breast Cancer and a Deleterious BRCA Mutation
  • Clinical Trial IDs

    NCT ID: NCT02282345

    ORG ID: 2014-0045

    NCI ID: NCI-2015-00335

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    BMN 673 Talazoparib tosylate BMN 673

    Trial Purpose

    The goal of this clinical research study is to learn if BMN 673 can help to control breast
    cancer that has a BRCA mutation. The safety of BMN 673 will also be studied.

    Detailed Description

    Study Drug Administration:

    Each study cycle is 28 days.

    If you are found to be eligible to take part in this study, you will take BMN 673 capsules
    by mouth 1 time each day at about the same time every morning.

    You will be given a study drug diary to write down what time you take BMN 673 and if you
    miss or vomit any doses. You will return your completed study drug diary and study drug
    bottles with any unused study drug to each study visit.

    If you have side effects, the study doctor may decide to lower your study drug dose or have
    you stop taking the drug. You may be able to restart the study drug at the same or a lower
    dose. The study doctor will discuss this with you.

    On the days that you have study visits, you will take your dose of study drug at the clinic.
    Do not take your dose of study drug at home on these days.

    Study Visits:

    On Day 1 of all cycles:

    - You will have a physical exam.

    - Blood (about 1 tablespoon) will be drawn for routine tests.

    Every week, blood (about 1 tablespoon) will be drawn for routine tests. If the study doctor
    approves it, you may not have to return to the clinic on Days 8 and 15 of Cycle 2. You may
    have these blood draws done at a local laboratory and have the results sent to the study
    doctor. Your study doctor will discuss this with you.

    On Days 1, 8, and 22 of Cycle 1 and Day 22 of Cycle 2, blood (about 1-2 tablespoons) will be
    drawn for biomarker, PGt, and proteomic testing.

    On Day 1 of Cycle 2, you will have an ultrasound of your breast(s) to check the status of
    the disease.

    After your last dose of Cycle 2:

    - You will have a physical exam.

    - Blood (about 1 tablespoon) will be drawn for routine tests.

    - You will have an ultrasound of your breast(s) to check the status of the disease.

    - You will have a core biopsy or an image-guided FNA to check the status of the disease
    and for biomarker, PGt, and proteomic testing.

    After Cycle 2, you will receive chemotherapy and/or have surgery to remove the tumor as part
    of the standard of care for the disease. You will be given a separate consent form that
    describes this procedure and its risks. During the surgery, some of the tissue that is
    removed will be collected to check the status of the disease and for biomarker, PGt, and
    proteomic testing. After the surgery, you may be called by the study doctor to ask how you
    are doing. This call should last about 10 minutes.

    Cell lines will be created using your collected tissue. Cell lines are blood or tissue
    cells that are grown in a laboratory or in research animals.

    Xenograft models will be created using your collected tissue. A xenograft is taking a
    graft of tissue from one donor and transplanting it into another. For this
    study, we will take a graft of your tissue and transplant it into a mouse to help us better
    understand BRCA mutations.

    Length of Treatment:

    You will receive up to 2 cycles of study drug. 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.

    Your participation on the study will be over after the surgery.

    This is an investigational study. BMN 673 is not FDA-approved or commercially available.
    It is currently being used for research purposes only. The study doctor can explain how the
    study drug is designed to work.

    Up to 20 participants will be enrolled in this study. All will take part at MD Anderson.

    Trial Arms

    Name Type Description Interventions
    BMN 673 Experimental BMN 673 administered by mouth at 1 mg per day for a total of 2 cycles before participants proceed to the standard of care therapy of the treating physician's choice. Each cycle will consist of 28 days. BMN 673

    Eligibility Criteria

    Inclusion Criteria:

    1. Signed written informed consent

    2. Histologically confirmed primary invasive adenocarcinoma of the breast with the size
    of the primary tumor being at least 1 cm on imaging by either mammography, ultrasound
    or breast MRI

    3. Negative HER-2/neu- disease defined as patients with FISH ratio <2.0 or <6.0 HER2
    gene copies per nucleus, and IHC staining scores of 0, 1+, or 2+.

    4. No prior treatment for primary invasive adenocarcinoma of the breast such as
    irradiation, chemotherapy, hormonal therapy, immunotherapy, investigational therapy
    or surgery. Subjects receiving hormone replacement treatment (HRT) are eligible if
    this therapy is discontinued at least 2 weeks before starting study therapy.
    Treatment for DCIS is allowed, such as surgery, hormonal therapy and radiotherapy.

    5. ECOG performance status of 0-1

    6. Baseline MUGA or echocardiogram scans with LVEF of > 50%.

    7. Patient must have adequate organ function as determined by the following laboratory
    values: a. ANC>/=1,500 /uL b. Platelets >/=100,000 / uL c. Hgb >/= 9 g/dL d.
    Creatinine clearance >50 ml/min e. Total bilirubin </= 1.5 X ULN f. ALT and AST < 2.5
    X ULN

    8. Men or women 18 years of age or older.

    9. Women of childbearing potential (WOCBP) must be using an adequate method of
    contraception to avoid pregnancy throughout the study and for up to 8 weeks after the
    last dose of investigational product in such a manner that the risk of pregnancy is
    minimized. For the purposes of this study, WOCBP will be considered 12 months without
    menstruation. Men on study also must be using contraception.

    10. Negative serum or urine pregnancy test for women within 72 hours of receiving the
    first dose of the study medication for women of childbearing potential as per
    institutional guidelines.

    11. Identified deleterious mutation in BRCA 1 or 2 genes ( this does not include variants
    of uncertain significance).

    12. Eligible to receive standard of care chemotherapy and/or surgery based upon standard
    practices or institutional guidelines.

    Exclusion Criteria:

    1. Women who are pregnant (including positive pregnancy test at enrollment or prior to
    study drug administration) or breast-feeding.

    2. Disease free of prior malignancy for < 5 years with the exception of curatively
    treated basal carcinoma of the skin or carcinoma in situ of the cervix.

    3. Any other previous antitumor therapies for the current cancer event. Treatment for
    DCIS is allowed, such as surgery, hormonal therapy and radiotherapy.

    4. Has had major surgery within 21 days before Cycle 1 Day 1

    5. Gastrointestinal tract disease or defect with associated malabsorption syndrome

    6. Uncontrolled inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)

    7. Myocardial infarction within 6 months before starting therapy, symptomatic congestive
    heart failure (New York Heart Association > class II), unstable angina, or unstable
    cardiac arrhythmia requiring medication

    8. Serious intercurrent infections or non-malignant medical illness that are
    uncontrolled or the control of which may be jeopardized by this therapy

    9. Psychiatric disorders or other conditions rendering the subject incapable of
    complying with the requirements of the protocols

    10. Unable to take oral medications

    11. Known to be human immunodeficiency virus positive

    12. Known active hepatitis C virus, or known active hepatitis B virus

    13. Concurrent disease or condition that would interfere with study participation or
    safety, such as any of the following: Active, clinically significant infection
    either grade > 2 by National Cancer Institute (NCI) Common Terminology Criteria for
    Adverse Events (CTCAE) v4.03 or requiring the use of parenteral anti-microbial agents
    within 14 days before Day 1 of study drug Clinically significant bleeding diathesis
    or coagulopathy, including known platelet function disorders Non-healing wound,
    ulcer, or bone fracture

    14. Known hypersensitivity to any of the components of BMN 673

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Toxicity of Using BMN 673 Prior to Initiating Standard Neoadjuvant Therapies

    Secondary Outcome Measures

    Clinical Response to BMN 673

    Trial Keywords

    Breast cancer

    BRCA deleterious mutation

    Invasive adenocarcinoma of the breast

    BMN 673

    Talazoparib tosylate