Clinical Trials /

T-DM1+Pertuzumab in Pre-OP Early-Stage HER2+ BRCA

NCT02326974

Description:

This research study is studying a combination of drugs as a possible treatment for breast cancer that has tested positive for a protein called HER2. The names of the study interventions involved in this study are: - Trastuzumab emtansine (also called T-DM1) - Pertuzumab

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">T-DM1</span>+<span class="go-doc-concept go-doc-intervention">Pertuzumab</span> in Pre-OP Early-Stage <span class="go-doc-concept go-doc-biomarker">HER2</span>+ BRCA

Title

  • Brief Title: T-DM1+Pertuzumab in Pre-OP Early-Stage HER2+ BRCA
  • Official Title: The Impact of HER2 Heterogeneity on the Treatment of Early-stage HER2-positive Breast Cancer: a Phase II Study of T-DM1 in Combination With Pertuzumab in the Preoperative Setting
  • Clinical Trial IDs

    NCT ID: NCT02326974

    ORG ID: 14-409

    Trial Conditions

    HER-2 Positive Breast Cancer

    Breast Cancer

    Stage II Breast Cancer

    Stage III Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    T-DM1 Kadcyla T-DM1 and Pertuzumab
    Pertuzumab Perjeta T-DM1 and Pertuzumab

    Trial Purpose

    This research study is studying a combination of drugs as a possible treatment for breast
    cancer that has tested positive for a protein called HER2.

    The names of the study interventions involved in this study are:

    - Trastuzumab emtansine (also called T-DM1)

    - Pertuzumab

    Detailed Description

    This research study is a Phase II clinical trial. Phase II clinical trials test the safety
    and effectiveness of an investigational intervention to learn whether the intervention works
    in treating a specific disease. "Investigational" means that the intervention is being
    studied. The FDA (the U.S. Food and Drug Administration) has not approved T-DM1 for
    pre-operative use in breast cancer but it has been approved for other uses in breast cancer.
    The FDA has approved pertuzumab as a pre-operative treatment.

    Trial Arms

    Name Type Description Interventions
    T-DM1 and Pertuzumab Experimental T-DM1 via IV every 3 weeks for 6 doses and Pertuzumab loading dose via IV on Cycle 1 Day 1 followed by maintenance dose via IV every 3 weeks for 6 doses. Excision of tumor/mastectomy of biopsy residual tumor T-DM1, Pertuzumab

    Eligibility Criteria

    Inclusion Criteria:

    - Patients must have HER2-positive Stage II or III histologically confirmed invasive
    carcinoma of the breast. A minimum tumor size of 2 cm determined by physical exam or
    imaging is required.

    - HER-2 positive, confirmed by central testing (Clarient labs): IHC 3+ and/or FISH
    positive based on one of the three following criteria:

    - Single-probe average HER2 copy number6.0 signals/cell OR

    - Dual-probe HER2/CEP17 <2.0 with an average HER2 copy number 6.0 signals/cell OR

    - Dual-probe HER2/CEP17 ratio 2.0

    - ER/PR determination is required.

    - Bilateral breast cancers are allowed if both cancers are HER2-positive.

    - Patients with multifocal or multicentric disease are eligible as long as one area
    meets eligibility criteria.

    - Breast imaging should include the ipsilateral axilla. For subjects with a clinically
    negative axilla, a sentinel lymph node biopsy will be performed either before or
    after preoperative therapy at the discretion of the subject's physicians. For
    subjects with a clinically positive axilla, a needle aspiration, core biopsy or SLN
    procedure will be performed to determine the presence of metastatic disease in the
    lymph nodes.

    - Men and women (with any menopausal status) 18 years of age

    - ECOG performance status 0 or 1

    - Required laboratory values:

    - ANC 1500/mm3

    - Hemoglobin 9 g/dl

    - Platelets 100,000/mm3

    - Serum creatinine < 1.5 X ULN (institutional)

    - Total bilirubin 1.0 X ULN (institutional) For patients with Gilbert syndrome,
    the direct bilirubin should be within the institutional normal range.

    - AST and ALT 1.5x ULN (institutional)

    - Alkaline phosphatase 1.5x ULN (institutional)

    - Documentation of hepatitis B virus (HBV) and hepatitis C virus (HCV) serologies is
    required: this includes hepatitis B surface antigen (HBsAg) and/or total hepatitis B
    core antibody (HBcAb) in addition to HCV antibody testing.

    - Only for patients who test positive for hep B/C virus: PTT/INR < ULN (institutional)

    - Left ventricular ejection fraction (LVEF) 55%

    - Premenopausal women must have a negative serum pregnancy test, including women who
    have had a tubal ligation and for women less than 12 months after the onset of
    menopause.

    - Women of childbearing potential and men with partners of childbearing potential must
    be willing to use one highly effective form of non-hormonal contraception or two
    effective forms of non-hormonal contraception by the patient and/or partner and
    continue its use for the duration of the study treatment and for 7 months after the
    last dose of study treatment.

    - Potent CYP3A4 inhibitors, such as ketoconazole and erythromycin, should be avoided
    during the study treatment period with T-DM1.

    - Excessive alcohol intake should be avoided (occasional use is permitted).

    - Patients with a history of ipsilateral DCIS are eligible.

    - Patients undergoing breast conservation therapy (i.e. lumpectomy) must not have any
    contraindications to radiation therapy.

    - Willing and able to sign informed consent.

    - Willing to provide tissue for research purposes.

    Exclusion Criteria:

    - Pregnant or nursing women due to the teratogenic potential of the study drugs.

    - Active, unresolved infection.

    - Receipt of intravenous antibiotics for infection within 7 days prior to enrollment.

    - Patients with active liver disease, for example, due to hepatitis B virus, hepatitis
    C virus, autoimmune hepatic disorder, or sclerosing cholangitis.

    - Uncontrolled hypertension (systolic >180 mm Hg and/or diastolic >100 mm Hg) or
    clinically significant (i.e. active) cardiovascular disease: cerebrovascular
    accident/stroke or myocardial infarction within 6 months prior to first study
    medication, unstable angina, congestive heart failure (CHF) of New York Heart
    Association (NYHA) Grade II or higher, or serious cardiac arrhythmia requiring
    medication.

    - Significant symptoms (Grade 2) peripheral neuropathy.

    - Other concurrent serious diseases that may interfere with planned treatment,
    including severe pulmonary conditions/illness, uncontrolled infections, uncontrolled
    diabetes.

    - Any prior treatment for the current breast cancer, including chemotherapy, hormonal
    therapy, radiation or experimental therapy.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Pathologic complete response (pCR)

    Secondary Outcome Measures

    Intratumor heterogeneity of HER2 amplification

    Clinical response

    Safety and tolerability of T-DM1 plus pertuzumab assessed by incidence of adverse events which will be reported by term and by maximum grade using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Enrichment for HER2-negativity or HER2 heterogeneity in residual tumors treated with T-DM1 plus pertuzumab preoperative therapy

    Disease-free and overall survival in patient groups defined by HER2 heterogeneity who are treated with T-DM1 plus pertuzumab

    Trial Keywords