Clinical Trials /

Trastuzumab Emtansine in Treating Older Patients With Human Epidermal Growth Factor Receptor 2-Positive Stage I-III Breast Cancer

NCT02414646

Description:

This phase II trial studies how well trastuzumab emtansine works in treating older patients with human epidermal growth factor receptor 2 (HER2)-positive stage I-III breast cancer. HER2 is a protein found on the surface of cancer cells that helps them to grow and spread. Trastuzumab emtansine may kill cancer cells by binding to HER2-positive on the surface of the tumor cells and blocking their ability grow and spread.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Trastuzumab Emtansine</span> in Treating Older Patients With Human Epidermal Growth Factor Receptor 2-Positive Stage I-III <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: Trastuzumab Emtansine in Treating Older Patients With Human Epidermal Growth Factor Receptor 2-Positive Stage I-III Breast Cancer
  • Official Title: Adjuvant Ado-Trastuzumab Emtansine (T-DM1) for Older Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02414646

    ORG ID: RU011301I

    NCI ID: NCI-2015-00468

    Trial Conditions

    Estrogen Receptor Negative

    HER2 Positive Breast Carcinoma

    Progesterone Receptor Negative

    Stage IB Breast Cancer

    Stage IIA Breast Cancer

    Stage IIB Breast Cancer

    Stage IIIA Breast Cancer

    Stage IIIC Breast Cancer

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    This phase II trial studies how well trastuzumab emtansine works in treating older patients
    with human epidermal growth factor receptor 2 (HER2)-positive stage I-III breast cancer.
    HER2 is a protein found on the surface of cancer cells that helps them to grow and spread.
    Trastuzumab emtansine may kill cancer cells by binding to HER2-positive on the surface of
    the tumor cells and blocking their ability grow and spread.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. Invasive disease-free survival (IDFS), defined as absence of all of the following:
    Ipsilateral invasive breast cancer recurrence, regional invasive breast cancer recurrence,
    distant recurrence, death attributable to any cause, contralateral invasive breast cancer,
    or second non-breast invasive cancer. Note: In-situ events are not included.

    SECONDARY OBJECTIVES:

    I. Overall survival (OS). II. Recurrence-free survival (RFS). III. Adverse events. IV.
    Cardiac function/adverse events. V. Site of first recurrence.

    TERTIATRY OBJECTIVES:

    I. The associations of adverse events and outcomes with each of the following will be
    examined: Geriatric assessment (GA), patient reported outcomes (Patient-Reported Outcomes
    Version of the Common Terminology Criteria for Adverse Event [PRO-CTCAE]), quality of life
    (QOL), and biomarkers of aging.

    II. To determine whether clinician-reported CTCAEs are more accurate when PRO-CTCAE data are
    shared with the patient and clinician.

    OUTLINE:

    Patients receive trastuzumab emtansine intravenously (IV) over 30-90 minutes on day 1.
    Treatment repeats every 21 days for 17 courses in the absence of disease progression or
    unacceptable toxicity.

    After completion of study treatment, patients are followed up at 6-12 months and then yearly
    for 4 years.

    Trial Arms

    Name Type Description Interventions
    Treatment (trastuzumab emtansine) Experimental Patients receive trastuzumab emtansine IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 17 courses in the absence of disease progression or unacceptable toxicity.

    Eligibility Criteria

    Inclusion Criteria:

    - HER2-positive disease, defined as immunohistochemistry (IHC) 3+ or amplification by
    fluorescent in situ hybridization (FISH) (HER2/chromosome 17 centromere [CEP17] ratio
    >= 2 or an average of >= 6 HER2 gene copies per nucleus) confirmed by Central
    Pathology Review (Mayo Clinic Rochester) prior to patient being registered to begin
    protocol therapy

    - NOTE: ductal carcinoma in situ (DCIS) components should not be counted in the
    determination of HER2 status

    - Stage I-III breast cancer with the following criteria met:

    - If node-negative or if node status unknown (because it was not assessed), tumor
    must be > 2 cm (T2 or T3 tumor) or have higher-risk T1c disease (defined as
    tumor > 1 cm and estrogen receptor [ER]-negative and progesterone-receptor [PR]
    negative); if some ER/PR staining is present, ER and PR negative are defined as
    being positive in < 10% cells (per local pathology read)

    - If node-positive (N1-N3), T1mi, T1a, T1b, T1c, T2, or T3 tumors are eligible

    - Definition of node-negative disease (when node status known): if the
    patient has had a negative sentinel node biopsy and/or a negative axillary
    dissection, then the patient is determined to be node-negative; axillary
    nodes with single cells or tumor clusters =< 0.2 mm by either hematoxylin
    and eosin (H&E) or IHC will be considered node-negative; any axillary lymph
    node with tumor clusters between 0.02 and 0.2 cm is considered a
    micrometastasis; patients with a micrometastasis are eligible; an axillary
    dissection is not required to be performed in patients with a positive
    sentinel node and management of the axilla will be left up to the treating
    provider; in cases where the specific pathologic size of lymph node
    involvement is subject to interpretation, the principal investigator will
    make the final determination as to eligibility; in these special
    situations, the investigator must document this approval in the patient
    medical record

    - ER/PR determination assays performed by IHC methods according to the local
    institution standard protocol

    - Standard chemotherapy/trastuzumab declined by patient OR patient is deemed by
    physician for any reason to not be a candidate for standard therapy (i.e. patient
    and/or provider choose not to pursue standard trastuzumab-based chemotherapy regimen
    because of concerns related to toxicity or patient preference)

    - For patients with bilateral breast cancers, each cancer individually meets criteria
    for enrollment OR the contralateral cancer does not meet criteria for adjuvant
    chemotherapy (i.e. small, node-negative, ER+, low grade cancer present
    contralaterally)

    - All tumor removed by either a modified radical mastectomy or a segmental mastectomy
    (lumpectomy)

    - NOTE: management of axillary lymph nodes is up to the treating provider;
    however, all surgical margins should be clear of invasive cancer or DCIS (i.e.,
    no tumor on ink); the local pathologist must document negative margins of
    resection in the pathology report; if all other margins are clear, a positive
    posterior (deep) margin is permitted, provided the surgeon documents that the
    excision was performed down to the pectoral fascia and all tumor has been
    removed; likewise, if all other margins are clear, a positive anterior
    (superficial; abutting skin) margin is permitted provided the surgeon documents
    that all tumor has been removed

    - =< 90 days from the patient's most recent breast surgery for this breast cancer

    - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2

    - Baseline ejection fraction >= 50% by multi gated acquisition scan (MUGA) scan or
    echocardiogram performed =< 60 days prior to registration

    - Absolute neutrophil count (ANC) >= 1500/mm^3

    - Platelet count >= 100,000/mm^3

    - Hemoglobin > 9.0 g/dL

    - Total bilirubin =< 1.5 x upper limit of normal (ULN)

    - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper
    limit of normal (ULN)

    - Alkaline phosphatase =< 2.5 x ULN

    - International normalized ratio (INR) < 1.5 x ULN for institution unless patient is on
    planned therapy with anticoagulants (i.e., warfarin) with higher target planned; in
    those cases, INR up to 3.5 is acceptable

    - Partial thromboplastin time (PTT) < 1.5 x ULN for institution unless patient is on
    planned therapy with heparin or heparin-like products

    - Life expectancy > 5 years

    - Willing to employ adequate and appropriate birth control if applicable

    - NOTE: This study is for patients aged 65 and older and most female patients will
    have entered menopause by this time; however patients should not become pregnant
    while on this study; pre-menopausal women need to use birth control while on
    this study and women should not breastfeed a baby while on this study; any man
    treated on this study will also need to use contraception if his partner is a
    premenopausal female; patients should check with their health care provider
    about what kind of birth control methods to use and how long to use them

    - Negative urine or serum pregnancy test done =< 7 days prior to
    registration/randomization, for women of childbearing potential only

    - NOTE: in the rare case that a woman enrolling on study is of childbearing
    potential, a pregnancy test is required prior to enrollment on study

    - Able to provide informed written consent

    - Willing to return to consenting institution for follow-up (during the active
    monitoring phase of the study)

    - Willing to provide blood samples for mandatory correlative research purposes

    Exclusion Criteria:

    - Evidence of metastatic disease

    - NOTE: patients will not require baseline staging positron emission tomography
    (PET) or computed tomography (CT) chest, abdomen, pelvis or bone scan to rule
    out metastatic disease prior to enrollment; any staging scans will be ordered at
    the treating provider's discretion; if metastatic disease is found on any
    staging studies done, patients will not be eligible for enrollment

    - Locally advanced tumors at diagnosis (T4), including tumors fixed to the chest wall,
    peau d'orange, skin ulcerations/nodules, or clinical inflammatory changes (diffuse
    brawny cutaneous induration with an erysipeloid)

    - Any T1a/T1b/T1c tumor that is node-negative/node-unknown AND ER OR PR positive

    - Positive hepatitis B (hepatitis B surface antigen and antibody) and/or hepatitis C
    (hepatitis C antibody test) as indicated by serologies conducted =< 3 months prior to
    starting study if liver function tests are outside of the normal institutional range

    - NOTE: patients with hepatitis B or C serologies indicating active infection
    without known active disease must meet the eligibility requirements for ALT,
    AST, total bilirubin, INR, PTT, and alkaline phosphatase on at least two
    consecutive occasions, separated by at least 1 week

    - Active liver disease, for example, due to autoimmune hepatic disorder, or sclerosing
    cholangitis

    - Significant cardiac disease or risk factors as indicated by MUGA or echocardiogram
    performed =< 60 days prior to registration

    - NOTE: patients are excluded from this study if there is a history of significant
    cardiac disease, cardiac risk factors or uncontrolled arrhythmias, symptomatic
    congestive heart failure, unstable angina pectoris, cardiac arrhythmia,
    including, but not limited to, the following:

    - Any prior myocardial infarction (asymptomatic changes on electrocardiogram
    [EKG] suggestive of old myocardial infarction [MI] is not an exclusion)

    - Documented congestive heart failure (CHF)

    - Current use of any therapy specifically for CHF

    - Current uncontrolled hypertension (diastolic > 100 mmHg or systolic > 200
    mmHg)

    - Clinically significant pericardial effusion

    - Co-morbid systemic illnesses or other severe concurrent disease which, in the
    judgment of the investigator, would make the patient inappropriate for entry into
    this study or interfere significantly with the proper assessment of safety and
    toxicity of the prescribed regimens

    - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
    infection or psychiatric illness/social situations that would limit compliance with
    study requirements

    - Currently receiving any other investigational agent which would be considered as a
    treatment for the primary neoplasm

    - Concurrent second malignancy or past malignancy with > 30% estimated risk of relapse
    in next 5 years; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the
    cervix; NOTE: if there is a history or prior malignancy, patient must not be
    receiving active treatment for this malignancy cancer

    - Any prior treatment with T-DM1 (trastuzumab emtansine) or any trastuzumab therapy

    - Any neoadjuvant chemotherapy

    - > 4 weeks of tamoxifen therapy, or other hormonal therapy, for adjuvant therapy for
    this malignancy

    - NOTE: if the patient has received < 4 weeks of such therapy but is still
    receiving it at the time of entry into the study, patient must temporarily stop
    the therapy; the therapy can re-start only after 12 weeks of T-DM1 has been
    administered

    - History of exposure at any time to the following cumulative doses of anthracyclines:

    - Doxorubicin or liposomal doxorubicin > 500 mg/m^2

    - Epirubicin > 900 mg/m^2

    - Mitoxantrone >120 mg/m^2

    - Another anthracycline, or more than one anthracycline used in a cumulative dose
    exceeding the equivalent of doxorubicin 500 mg/m^2

    - History of intolerance (including grade 3 or 4 infusion reactions) to murine proteins

    - History of previous invasive breast cancer =< 5 years

    - NOTE: history of DCIS, lobular carcinoma in situ (LCIS) is allowed

    Minimum Eligible Age: 65 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Invasive Disease Free Survival rate (IDFS)

    Secondary Outcome Measures

    Overall Survival (OS)

    Recurrence-free survival

    Incidence of adverse events

    Cardiac dysfunction defined as incidence of symptomatic left ventricular systolic dysfunction, cardiac death, and incidence of decrease in ejection fraction by at least 10 percentage points below baseline or to below 50%

    Site of first recurrence

    Trial Keywords