Clinical Trials /

Palbociclib in Treating Patients With Metastatic HER-2 Positive Breast Cancer With Brain Metastasis

NCT02774681

Description:

The purpose of this study is to evaluate if the study drug palbociclib has anti-tumor activity against the breast cancer that has spread to the brain and also to determine the overall radiographic response rate in the CNS. Palbociclib is an anti-cancer medication that has been shown to stop cancer cells from growing. It has been approved in hormone positive breast cancer, along with other hormone therapies and has been found to be effective. The preclinical studies suggest that the drug may also have activity in other types of breast cancer, such as HER2 positive breast cancer. The purpose of this study is to see if the study drug is effective in patients with brain metastasis, who have HER2-positive breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Palbociclib</span> in Treating Patients With Metastatic <span class="go-doc-concept go-doc-biomarker">HER-2</span> Positive or <span class="go-doc-concept go-doc-keyword">Triple-Negative</span> Breast Cancer With <span class="go-doc-concept go-doc-disease">Brain Metastasis</span>

Title

  • Brief Title: Palbociclib in Treating Patients With Metastatic HER-2 Positive or Triple-Negative Breast Cancer With Brain Metastasis
  • Official Title: A Phase II Single Arm Study of Palbociclib in Patients With Metastatic HER2-Positive and Triple Negative Breast Cancer With Brain Metastasis
  • Clinical Trial IDs

    NCT ID: NCT02774681

    ORG ID: NU 15B08

    NCI ID: STU00202582

    Trial Conditions

    Breast Carcinoma Metastatic in the Brain

    Estrogen Receptor Negative

    HER2/Neu Negative

    HER2/Neu Positive

    Progesterone Receptor Negative

    Recurrent Breast Carcinoma

    Stage IV Breast Cancer

    Triple-Negative Breast Carcinoma

    Trial Interventions

    Drug Synonyms Arms
    Palbociclib Ibrance, PD-0332991, PD-332991 Treatment (palbociclib)

    Trial Purpose

    The purpose of this study is to evaluate if the study drug palbociclib has anti-tumor
    activity against the breast cancer that has spread to the brain and also to determine the
    overall radiographic response rate in the CNS. Palbociclib is an anti-cancer medication that
    has been shown to stop cancer cells from growing. It has been approved in hormone positive
    breast cancer, along with other hormone therapies and has been found to be effective. The
    preclinical studies suggest that the drug may also have activity in other types of breast
    cancer, such as triple negative and HER2 positive breast cancer. The purpose of this study
    is to see if the study drug is effective in patients with brain metastasis, who have triple
    negative and HER2-positive breast cancer.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To determine the radiographic response rate in the central nervous system (CNS) in
    patients with TNBC and HER2-positive breast cancer who have brain metastasis treated with
    palbociclib.

    SECONDARY OBJECTIVES:

    I. To determine the progression-free survival (PFS) and overall survival (OS) in patients
    with TNBC and HER2-positive breast cancer who have brain metastasis treated with
    palbociclib.

    II. To determine time to CNS progression in patients with TNBC and HER2-positive breast
    cancer who have brain metastasis treated with palbociclib.

    III. To determine systemic overall response rate (ORR) in patients with TNBC and
    HER2-positive breast cancer who have brain metastasis treated with palbociclib.

    IV. To determine the safety and tolerability of palbociclib in patients with TNBC and
    HER2-positive breast cancer.

    TERTIARY OBJECTIVES:

    I. To evaluate circulating tumor deoxyribonucleic acid (DNA) at baseline, 2 month and 4
    months; particularly to assess cyclin D1 aberrations, and if this is predictive of
    responses.

    II. To evaluate genomic landscape of available CNS and non-CNS tumors, and describe any
    discordance.

    III. To evaluate cognitive function and quality of life at baseline, 2 and 4 months in
    patients receiving palbociclib.

    OUTLINE:

    Patients receive palbociclib orally (PO) daily on days 1-21. Courses repeat every 28 days in
    the absence of disease progression or unacceptable toxicity. Patients with HER2 positive
    breast cancer may also receive trastuzumab intravenously (IV) as standard of care
    concurrently with palbociclib.

    After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months, and
    then every 6 months for up to 3 years.

    Trial Arms

    Name Type Description Interventions
    Treatment (palbociclib) Experimental Patients receive palbociclib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with HER2 positive breast cancer may also receive trastuzumab IV over 30-90 minutes every 3 weeks. Palbociclib

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically confirmed triple negative or HER2-positive metastatic breast cancer
    (estrogen and progesterone receptor 0%, HER-2 3+ by immunohistochemistry (IHC); if
    IHC score of 2, fluorescence in situ hybridization (FISH) ratio must be greater than
    2.0; if FISH less than 2.0, HER2 copy number must be greater than 6; NOTE: Brain
    lesions are not required to have pathologic confirmation

    - Patients should not have received > 2 lines of chemotherapy for metastatic disease

    - Patients must have a life expectancy of at least 12 weeks at the time of registration

    - Eastern Cooperative Oncology Group (ECOG) performance status >= 2

    - Measurable disease in the brain, defined as at least 1 lesion measuring >= 5 mm on
    imaging at the time of registration

    - If patients are on corticosteroids, they must have been on a stable or decreasing
    dose >= 5 days prior to obtaining their baseline gadolinium (Gd)-magnetic resonance
    imaging (MRI) of brain; this MRI is to be obtained within 28 days of registration;
    NOTE: If patient needs escalation of steroids prior to therapy, or are on unstable
    doses of steroids they are not eligible

    - Patients who underwent neurosurgery (NSGY) or stereotactic radiosurgery (SRS) to a
    brain lesion must have a new measureable lesion; NOTE: SRS may be done to a lesion
    that will not be used for response evaluation and should be done > 2 weeks prior to
    registration; any NSGY procedure must have been completed > 3 weeks prior to
    registration

    - Patients must not have received systemic therapy within 2 weeks of initiating
    palbociclib; NOTE: For the HER2-positive cohort, patients on trastuzumab can remain
    on the drug; no break or washout period required; however, lapatinib,
    ado-trastuzumab-emtansine, and pertuzumab are prohibited and a minimum wash out
    period of 2 weeks is required

    - Patients must exhibit adequate bone marrow, liver, and renal function, within 14 days
    prior to registration, defined as:

    - Absolute neutrophil count (ANC) >= 1,000/mm^3 (growth factor support is
    permitted)

    - Platelets >= 100,000/mm^3 (may be reached by transfusion)

    - Hemoglobin >= 10 gm/dl (may be reached by transfusion)

    - Glutamate pyruvate transaminase (GPT)/glutamate oxaloacetate transaminase (GOT)
    < 3 x upper limit of normal (ULN) (or < 5 x ULN in case of liver metastasis)

    - Bilirubin < 3 x ULN (or < 5 x ULN in case of liver metastasis)

    - Creatinine < 1.5 x ULN

    - Females of child-bearing potential (FOCBP) and males must agree to use adequate
    contraception prior to study entry, for the duration of study participation, and for
    2 weeks following completion of therapy; should a female patient become pregnant or
    suspect she is pregnant while participating in this study, she should inform her
    treating physician immediately; likewise, if the female partner of a male patient
    becomes pregnant while participating in this study, he should inform his treating
    physician immediately; NOTE: A FOCBP is any woman (regardless of sexual orientation,
    having undergone a tubal ligation, or remaining celibate by choice) who meets the
    following criteria:

    - Has not undergone a hysterectomy or bilateral oophorectomy

    - Has had menses at any time in the preceding 12 consecutive months (and therefore
    has not been naturally postmenopausal for > 12 months)

    - Female patients must have a negative urine pregnancy test within 7 days prior to
    registration; if urine test is positive, it should be followed by serum pregnancy
    test

    - Patients must sign an informed consent prior to registration and before undergoing
    any study-specific procedures indicating that they are aware of the investigational
    nature of this study

    - Patient must have the ability to swallow and retain oral medication

    - Patient must have the ability to comply with all study requirements

    Exclusion Criteria:

    - Any uncontrolled neurological symptom attributed to CNS metastasis

    - Brain metastasis must not be impending herniation or other significant vasogenic
    edema requiring increasing steroid doses; lesions must not have frank hemorrhage

    - Patients with leptomeningeal disease are not eligible for participation

    - Any significant medical illnesses or infection that, in the investigator's opinion,
    cannot be adequately controlled with appropriate therapy or would compromise the
    patient's ability to tolerate this therapy are not eligible for participation

    - Known human immunodeficiency virus (HIV) positive status

    - Known active hepatitis B and/or C

    - Previous treatment with palbociclib

    - Patients who have a history of allergic reactions attributed to compounds of similar
    chemical or biologic composition to palbociclib are not eligible; AND/OR patients who
    have had prior exposure to compounds of similar chemical or biologic composition to
    palbociclib are not eligible hypersensitivity to any component of palbociclib are not
    eligible for participation

    - Patients being treated with any other experimental agents/clinical trials are not
    eligible for participation; if the patient is on any investigational agent, a
    wash-out period of minimum 2 weeks prior to registration is mandatory for the patient
    to be eligible for the study

    - Patients who are on any prohibited medication; a wash-out period of minimum 2 weeks
    prior to registration is mandatory for the patient to be eligible for the study

    - Inability to swallow capsules, malabsorption syndrome or gastrointestinal disease
    that severely affects the absorption of study drugs, major resection of the stomach
    or small bowel, or gastric bypass procedure

    - Patients who have an uncontrolled intercurrent illness including, but not limited to
    any of the following, are not eligible:

    - Ongoing or active infection requiring systemic treatment

    - Symptomatic congestive heart failure

    - Unstable angina pectoris

    - Cardiac arrhythmia: except atrial fibrillation (AF) and supraventricular
    tachycardia (SVT) that are controlled by medication

    - Psychiatric illness/social situations that would limit compliance with study
    requirements

    - Any other illness or condition that the treating investigator feels would
    interfere with study compliance or would compromise the patient's safety or
    study endpoints

    - Female patients who are pregnant or nursing are not eligible

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Radiographic response rate in the CNS in patients with TNBC and HER2- positive breast cancer who have brain metastasis treated with palbociclib

    Secondary Outcome Measures

    Incidence of Adverse Events

    Overall Survival (OS)

    Progression Free Survival (PFS)

    Overall Response Rate (ORR)

    Time to CNS progression

    Trial Keywords