Clinical Trials /

Whole-Brain Radiation Therapy or Stereotactic Radiosurgery With or Without Lapatinib Ditosylate in Treating Patients With Brain Metastasis From HER2-Positive Breast Cancer

NCT01622868

Description:

This randomized phase II trial studies how well whole-brain radiation therapy or stereotactic radiosurgery with or without lapatinib ditosylate works in treating patients with breast cancer that has too many of a protein called human epidermal growth factor receptor 2 (HER2) on its cells and has spread to the brain. Radiation therapy uses high energy x rays to kill tumor cells and shrink tumors. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may kill more tumor cells and cause less damage to normal tissue. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether whole-brain radiation therapy or stereotactic radiosurgery together with lapatinib ditosylate is an effective treatment for brain metastasis from breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Whole-Brain <span class="go-doc-concept go-doc-intervention">Radiation</span> Therapy With or Without <span class="go-doc-concept go-doc-intervention">Lapatinib Ditosylate</span> in Treating Patients With <span class="go-doc-concept go-doc-disease">Brain Metastasis</span> From <span class="go-doc-concept go-doc-biomarker">HER2</span>-Positive <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: Whole-Brain Radiation Therapy With or Without Lapatinib Ditosylate in Treating Patients With Brain Metastasis From HER2-Positive Breast Cancer
  • Official Title: Phase II Randomized Study of Whole Brain Radiotherapy in Combination With Concurrent Lapatinib in Patients With Brain Metastasis From HER2-Positive Breast Cancer: A Collaborative Study of NRG Oncology and KROG
  • Clinical Trial IDs

    NCT ID: NCT01622868

    ORG ID: NCI-2012-01977

    NCI ID: NCI-2012-01977

    Trial Conditions

    HER2/Neu Positive

    Male Breast Carcinoma

    Metastatic Malignant Neoplasm in the Brain

    Recurrent Breast Carcinoma

    Stage IV Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Lapatinib Ditosylate LAPATINIB DITOSYLATE, Tykerb Arm II (lapatinib ditosylate, WBRT)

    Trial Purpose

    This randomized phase II trial studies how well whole-brain radiation therapy (WBRT) with or
    without lapatinib ditosylate works in treating patients with breast cancer that has too many
    of a protein called human epidermal growth factor receptor 2 (HER2) on its cells and has
    spread to the brain. Radiation therapy uses high energy x rays to kill tumor cells.
    Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes
    needed for cell growth. It is not yet known whether radiation therapy together with
    lapatinib ditosylate is an effective treatment for brain metastasis from breast cancer.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To determine if there is a signal for an increase in complete response (CR) rate in the
    brain at 12 weeks post whole-brain radiotherapy (WBRT) as determined by magnetic-resonance
    imaging (MRI) scan of the brain, with the addition of lapatinib (lapatinib ditosylate) to
    WBRT compared to WBRT alone.

    SECONDARY OBJECTIVES:

    I. To evaluate CR rate in the brain at 4 weeks post WBRT as determined by MRI scan of the
    brain, with the addition of lapatinib to WBRT compared to WBRT alone.

    II. To evaluate objective response rate in the brain at 4 and 12 weeks post WBRT as
    determined by MRI scan of the brain, with the addition of lapatinib to WBRT compared to WBRT
    alone.

    III. To evaluate lesion-specific objective response rate (CR + partial response [PR]) at 4
    and 12 weeks post WBRT.

    IV. To evaluate overall response with addition of lapatinib to WBRT compared to WBRT alone.

    V. To evaluate the central nervous system (CNS) progression-free survival (PFS) rate and
    overall survival (OS) rate, with the addition of lapatinib to WBRT compared to WBRT alone.

    VI. To evaluate treatment-related adverse events when adding lapatinib to WBRT compared to
    WBRT alone.

    OUTLINE: Patients are randomized to 1 of 2 treatment arms.

    ARM I: Patients undergo WBRT once daily (QD) 5 days a week for 3 weeks.

    ARM II: Patients receive lapatinib ditosylate orally (PO) QD on days 1-42 and undergo WBRT
    as in Arm I.

    After completion of study treatment, patients are followed up at 4 and 12 weeks and then
    every 12 weeks thereafter.

    Trial Arms

    Name Type Description Interventions
    Arm I (WBRT) Experimental Patients undergo WBRT QD 5 days a week for 3 weeks.
    Arm II (lapatinib ditosylate, WBRT) Experimental Patients receive lapatinib ditosylate PO QD on days 1-42 and undergo WBRT as in Arm I. Lapatinib Ditosylate

    Eligibility Criteria

    Inclusion Criteria:

    - Pathologically (histologically or cytologically) proven diagnosis of invasive breast
    cancer

    - HER2-overexpressing breast cancer (3+ staining by immunohistochemistry or HER2 gene
    amplification by fluorescent in situ hybridization [FISH] or silver in situ
    hybridization [SISH] >= 2.0)

    - At least 1 measurable, unirradiated parenchymal brain metastasis within 21 days prior
    to study entry; the minimum size as measured on T1-weighted gadolinium-enhanced MRI
    must be as follows according to the number of brain metastases:

    - For a single solitary lesion the size must be >= 10 mm

    - For 2 or more lesions, the size of at least 2 of the lesions must be >= 5 mm

    - Patients may also have the following provided the size requirements above are
    met:

    - Progressive parenchymal brain metastasis following stereotactic
    radiosurgery for 1-3 brain metastases, with at least 1 new measurable
    lesion

    - Progressive parenchymal brain metastasis following surgical resection of
    1-3 brain metastases, with at least 1 measurable brain lesion

    - History/physical examination within 21 days prior to study entry

    - Karnofsky performance status >= 60% within 21 days prior to study entry

    - Able to swallow and retain oral medication (note: for patients unable to swallow
    tablets, an oral suspension preparation is acceptable)

    - Absolute neutrophil count (ANC) >= 1,200 cells/mm^3

    - Platelets >= 70,000 cells/mm^3

    - Hemoglobin >= 8.0 g/dL (note: the use of transfusion or other intervention to achieve
    hemoglobin [Hgb] >= 8.0 g/dL is acceptable)

    - Creatinine < 1.5 times institutional upper limit of normal

    - Bilirubin < 1.5 times institutional upper limit of normal

    - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 times
    institutional upper limit of normal with or without liver metastasis

    - Patient must provide study specific informed consent prior to study entry

    - Women of childbearing potential must have a negative serum pregnancy test within 21
    days prior to study entry

    - Sexually active women of childbearing potential and sexually active men must practice
    adequate contraception during therapy and for 12 months after protocol treatment
    completion

    - Prior lapatinib is allowed as long as the last dose received was > 21 days prior to
    study entry and provided the patient has not received it at any time after the
    diagnosis of brain metastasis

    Exclusion Criteria:

    - Prior WBRT

    - Prior radiation therapy (RT) (any site) with concurrent lapatinib defined as 1 or
    more days on which the patient received both radiation therapy and lapatinib on the
    same day

    - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
    infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
    arrhythmia, or psychiatric illness/social situations that would limit compliance with
    study requirements

    - Prior invasive malignancy (except non-melanomatous skin cancer, curatively resected
    thyroid papillary carcinoma, and invasive and non-invasive cancers related to the
    breast cancer) unless disease free for a minimum of 3 years

    - Leptomeningeal disease

    - Prior radiotherapy to the region of the study cancer that would result in overlap of
    radiation therapy fields except patients who have progressed following stereotactic
    radiosurgery for 1-3 brain metastases, with at least one new lesion

    - Severe, active co-morbidity, defined as follows:

    - Unstable angina and/or congestive heart failure requiring hospitalization within
    the last 6 months

    - Transmural myocardial infarction within the last 6 months

    - Acute bacterial or fungal infection requiring intravenous antibiotics at the
    time of study entry

    - Chronic obstructive pulmonary disease exacerbation or other respiratory illness
    requiring hospitalization or precluding study therapy at the time of study entry

    - Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
    hepatic or biliary disease that is acute or currently active or that requires
    antiviral therapy (with the exception of patients with Gilbert's syndrome,
    asymptomatic gallstones, liver metastases, or stable chronic liver disease per
    investigator assessment)

    - History of left ventricular ejection fraction (LVEF) below institutional normal
    unless repeated and within institutional normal range within 90 days of study
    entry

    - Grade 2 or greater rash of any cause at time of study entry

    - Grade 2 or greater diarrhea of any cause at time of study entry

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    CR rate in the brain measured by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 based on MRI scan of the brain

    Secondary Outcome Measures

    CNS PFS

    CR rate in the brain measured using revised RECIST version 1.1 based on MRI scan of the brain

    Incidence of treatment-related toxicity as measured by Common Terminology Criteria for Adverse Events version 4

    Lesion-specific ORR (CR + PR)

    Lesion-specific ORR (CR + PR)

    Objective response rate (ORR) (CR + PR) measured using RECIST version 1.1 based on MRI scan of the brain

    ORR (CR + PR) measured using RECIST version 1.1 based on MRI scan of the brain

    OS

    Overall response (CR, PR, or stable disease [SD])

    PFS

    Trial Keywords