Clinical Trials /

Cabozantinib +/- Trastuzumab In Breast Cancer Patients w/ Brain Metastases

NCT02260531

Description:

This research study is evaluating the effectiveness of the drug called cabozantinib (alone or in combination with trastuzumab) as a possible treatment for advanced breast cancer in which the cancer has spread to the brain.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Cabozantinib</span> +/- <span class="go-doc-concept go-doc-intervention">Trastuzumab</span> In <span class="go-doc-concept go-doc-disease">Breast Cancer</span> Patients w/ Brain Metastases

Title

  • Brief Title: Cabozantinib +/- Trastuzumab In Breast Cancer Patients w/ Brain Metastases
  • Official Title: A Phase II Study of Cabozantinib Alone or in Combination With Trastuzumab in Breast Cancer Patients With Brain Metastases
  • Clinical Trial IDs

    NCT ID: NCT02260531

    ORG ID: 14-359

    Trial Conditions

    Breast Cancer

    Brain Tumor - Metastatic

    Trial Interventions

    Drug Synonyms Arms
    Cabozantinib Cometriq ARM 1, ARM 2, ARM 3
    Trastuzumab Herceptin ARM 1

    Trial Purpose

    This research study is evaluating the effectiveness of the drug called cabozantinib (alone
    or in combination with trastuzumab) as a possible treatment for advanced breast cancer in
    which the cancer has spread to the brain.

    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 cabozantinib for your
    specific disease but it has been approved for other uses.

    Few treatments exist for brain metastases from breast cancer. Radiation and surgery are
    generally included as a possible standard of care treatments for this diagnosis.

    In this research study, the investigator are looking at how well cabozantinib works in
    treating breast cancer that has spread to the brain. Cabozantinib has been used in some
    phase I studies and information from those other research studies suggests that cabozantinib
    may help to shrink or stabilize the participant's breast cancer. In addition, information
    from these studies has shown that cabozantinib may pass through the blood brain barrier (a
    protective layer that prevents most large molecules and cells found in the blood from
    entering the brain tissue) and may be an effective treatment for brain metastases.

    If the participant has HER2-positive breast cancer, they will receive trastuzumab in
    addition to cabozantinib. Trastuzumab is an FDA approved drug for the treatment of
    HER2-positive metastatic breast cancer. However, the combination of cabozantinib and
    trastuzumab has not yet been tested. Trastuzumab may help to shrink or stabilize breast
    cancer in combination with cabozantinib. If the participant's breast cancer is
    HER2-negative, they will not receive trastuzumab as part of this clinical trial.

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

    - Cabozantinib (XL184)

    - Trastuzumab (herceptin) (participants with HER2-positive disease only)

    Trial Arms

    Name Type Description Interventions
    ARM 1 Experimental HER2-positive Cabozantinib- orally administered daily per treatment cycle Trastuzumab- IV administered once per cycle MRI- Baseline, Cycle 2 Day 1, and every 2 cycles Magnetic Resonance Angiography (MRA ), Baseline, Cycle 2 Day 1, Cabozantinib, Trastuzumab
    ARM 2 Experimental Hormone receptor-positive (ER+ and/or PR+) Cabozantinib- orally administered daily per treatment cycle MRI- Baseline, Cycle 2 Day 1, and every 2 cycles Magnetic Resonance Angiography (MRA ), Baseline, Cycle 2 Day 1, Cabozantinib
    ARM 3 Experimental Triple negative (ER-, PR-, HER2-) Cabozantinib- orally administered daily per treatment cycle MRI- Baseline, Cycle 2 Day 1, and every 2 cycles Magnetic Resonance Angiography (MRA ), Baseline, Cycle 2 Day 1, Cabozantinib

    Eligibility Criteria

    Inclusion Criteria:

    - Patients must have histologically or cytologically confirmed invasive breast cancer,
    with stage IV disease.

    - New or progressive CNS lesions, as assessed by the patient's treating physician.

    - For patients who have received prior cranial radiation, no increase in corticosteroid
    dose in the week prior to the baseline brain MRI

    - Discontinued prior therapy (with the exception of trastuzumab for patients with HER2+
    breast cancer)

    - Recovery to baseline or Grade 1 CTCAE v.4.0 from toxicities related to any prior
    treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive
    therapy;

    - The subject has an ECOG performance status of 0 or 1

    - Patients must have normal organ and marrow function and laboratory values as follows
    within 4 days before the first dose of cabozantinib

    - Sexually active subjects (men and women) must agree to use medically accepted barrier
    methods of contraception (e.g., male or female condom) during the course of the study
    and for 4 months after the last dose of study drug(s)

    - Subjects of childbearing potential must not be pregnant at screening.

    - Patients on bisphosphonates may continue receiving bisphosphonate therapy during
    study. Patients wanting to initiate bisphosphonate therapy may do so.

    - The subject has had an assessment of all known disease sites eg, by computerized
    tomography (CT) scan, magnetic resonance imaging (MRI), bone scan as appropriate,
    within 28 days before the first dose of cabozantinib

    Exclusion Criteria:

    - The subject has received cabozantinib or another c-Met inhibitor (please note ARQ 197
    is not considered a MET inhibitor for purposes of this study given data to suggest it
    inhibits tubulin)

    - The subject has uncontrolled, significant intercurrent or recent illness

    - Leptomeningeal disease as the only site of CNS involvement

    - Known contraindication to MRI with gadolinium contrast, such as cardiac pacemaker,
    shrapnel, or ocular foreign body

    - More than 2 seizures over the last 4 weeks prior to study entry

    - Grade 1 or higher CNS hemorrhage on baseline brain MRI, or history of grade 2 or
    higher CNS hemorrhage within 12 months

    - The subject has tumor in contact with, invading or encasing any major blood vessels

    - The subject has evidence of tumor invading the GI tract (esophagus, stomach, small or
    large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor
    within 28 days before the first dose of cabozantinib

    - The subject requires concomitant treatment, in therapeutic doses, with
    anticoagulants. Low dose aspirin ( 81 mg/day), low-dose warfarin ( 1 mg/day), and
    prophylactic LMWH are permitted.

    - The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test
    1.3 the laboratory ULN within 7 days before the first dose of cabozantinib.

    - Inability to swallow intact tablets

    - Diagnosis of another malignancy within 2 years before the first dose of cabozantinib,
    except for superficial skin cancers, or localized, low grade tumors deemed cured and
    not treated with systemic therapy

    - Subjects with clinically relevant ongoing complications from prior radiation therapy
    are not eligible

    - The subject is known to be positive for the human immunodeficiency virus (HIV)

    - Subjects with clinically relevant ongoing complications from prior surgery are not
    eligible

    - QTcF > 500 msec on average of screening EKGs performed within 28 days of first dose
    of cabozantinib. Three EKGs must be performed at screening. If the average of these
    three consecutive results for QTcF is > 500 msec, the subject is ineligible.

    - Active infection requiring IV antibiotics at Day 1 of cycle 1

    - No prior lapatinib within 7 days prior to initiation of protocol treatment

    - Previously identified allergy or hypersensitivity to components of the cabozantinib
    formulations

    - The subject requires chronic concomitant treatment with strong CYP3A4 inducers

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    CNS Objective Response Rate

    Secondary Outcome Measures

    CNS Objective Response Rate

    CNS Objective Response Rate

    CNS Objective Response Rate

    ORR in non-CNS

    Progression Free Survival Rate

    Clinical benefit rate

    First Progression Rate (CNS versus non-CNS)

    Overall Survival (OS) Rate

    Participants will be grouped as to whether or not their tumor has amplified Met

    To evaluate the incidence of c-Met amplified circulating tumor cells at baseline

    To evaluate potential plasma biomarkers of cabozantinib when given in combination with trastuzumab

    To assess vascularity of CNS tumors, through descriptive analysis as a composite of tumor vessel size, cerebral blood volume, cerebral blood flow, perfusion, and diffusion before and after exposure to cabozantinib by research MRIs

    To assess the number of participants with Adverse Events

    Trial Keywords

    Metastatic breast cancer and brain metastases

    HER-2 Positive Breast Cancer

    ER-Positive PR-Positive HER-2 Negative Breast Cancer

    ER-Negative PR-Negative HER2-Negative Breast Cancer