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Intrathecal Pertuzumab and Trastuzumab in Patients With New Untreated Asymptomatic or Low Symptomatic Brain Metastasis in HER2 Positive Breast Cancer

NCT02598427

Description:

The purpose of this research study is to determine how well pertuzumab and trastuzumab works in treating breast cancer that has spread to the brain. Pertuzumab and trastuzumab are treatments that stop breast cancer cells from growing abnormally by inhibiting (or blocking) members of a family of proteins that include Human Epidermal Growth Factor Receptor 2 (HER2). Pertuzumab and trastuzumab have been found to be very effective for HER2-positive breast cancer and are FDA approved for treatment of metastatic breast cancer outside of the brain when given through the vein. This suggests that pertuzumab and trastuzumab may help shrink or stabilize HER2-positive breast cancer that has spread to the brain in this research study. In this research study, the investigators are looking to see whether pertuzumab and trastuzumab will work to decrease the size of or stabilize breast cancer that has spread to the brain.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Intrathecal <span class="go-doc-concept go-doc-intervention">Pertuzumab and Trastuzumab</span> in Patients With New Untreated Asymptomatic or Low Symptomatic Brain Metastasis in <span class="go-doc-concept go-doc-biomarker">HER2</span> Positive Breast Cancer

Title

  • Brief Title: Intrathecal Pertuzumab and Trastuzumab in Patients With New Untreated Asymptomatic or Low Symptomatic Brain Metastasis in HER2 Positive Breast Cancer
  • Official Title: Phase I Dose Escalation Trial of Intrathecal Pertuzumab and Trastuzumab in Patients With New Untreated Asymptomatic or Low Symptomatic Brain Metastasis
  • Clinical Trial IDs

    NCT ID: NCT02598427

    ORG ID: Pro00061309

    Trial Conditions

    HER2 Positive Untreated Metastatic Breast Cancer

    Asymptomatic or Low Symptomatic Brain Metastasis in Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Pertuzumab Perjeta Intrathecal Pertuzumab and Trastuzumab
    Trastuzumab Herceptin Intrathecal Pertuzumab and Trastuzumab

    Trial Purpose

    The purpose of this research study is to determine how well pertuzumab and trastuzumab works
    in treating breast cancer that has spread to the brain. Pertuzumab and trastuzumab are
    treatments that stop breast cancer cells from growing abnormally by inhibiting (or blocking)
    members of a family of proteins that include Human Epidermal Growth Factor Receptor 2
    (HER2).

    Pertuzumab and trastuzumab have been found to be very effective for HER2-positive breast
    cancer and are FDA approved for treatment of metastatic breast cancer outside of the brain
    when given through the vein. This suggests that pertuzumab and trastuzumab may help shrink
    or stabilize HER2-positive breast cancer that has spread to the brain in this research
    study.

    In this research study, the investigators are looking to see whether pertuzumab and
    trastuzumab will work to decrease the size of or stabilize breast cancer that has spread to
    the brain.

    Detailed Description

    Intrathecal administration of pertuzumab and trastuzumab will occur via lumbar puncture
    under fluoroscopic guidance by interventional radiology at Duke University Medical Center.
    If pharmacokinetics are needed during the lumbar puncture at that cycle, 3 mL of CSF will be
    collected (a minimum of 2 mL of CSF is needed for PK testing). If pharmacokinetics are not
    needed during the lumbar puncture at that cycle, 3 mL of CSF will be removed to allow for
    injection of an equivalent volume of intrathecal therapy. Once the CSF is removed, the
    intrathecal pertuzumab and trastuzumab will be administered using aseptic technique.

    Patients will be treated using a 3+3 dose-escalation design. Patients will not be accrued to
    the next cohort (dose escalation) until at least one patient on the previous cohort has been
    followed for six weeks. If a dose limiting toxicity (DLT) is seen in a patient then the
    cohort will be expanded by an additional 3 patients to allow for 1 in 6 patients per cohort
    to have a DLT before dose escalation. Dose limiting toxicity will be assessed weekly during
    the first six weeks of the treatment.

    Patients will be treated weekly for the first six weeks and then every 3 weeks (q21 days).
    Once the maximum tolerated dose is reached, an additional 12 patients will be enrolled in
    the cohort at the maximum tolerated dose. The maximum number of enrolled patients is 36.
    Dosing is as follows: Cohort 1 - 80mg IT trastuzumab, 10mg IT pertuzumab, cohort 2 - 80mg IT
    trastuzumab, 20mg IT pertuzumab, cohort 3 - 80mg IT trastuzumab, 40mg IT pertuzumab, cohort
    4 - 80mg IT trastuzumab, 80mg IT pertuzumab. If the lowest dose level is found to be too
    toxic, the trial will stop without finding a maximum tolerated dose.

    Trial Arms

    Name Type Description Interventions
    Intrathecal Pertuzumab and Trastuzumab Experimental Four cohorts will enroll in a dose escalation of pertuzumab and a consistent dose of trastuzumab. The cohorts will be assigned as follows: Cohort: Intrathecal Dose: 10mg pertuzumab, 80mg trastuzumab 20mg pertuzumab, 80mg trastuzumab 40mg pertuzumab, 80mg trastuzumab 80mg pertuzumab, 80mg trastuzumab Pertuzumab, Trastuzumab

    Eligibility Criteria

    Inclusion Criteria:

    - HER2 positive by 2013 ASCO-CAP guidelines (IHC 3+ and/or FISH positive; IHC 2+ HER2
    patients are eligible with reflex FISH positive testing with the ratio 2.0) breast
    cancer patients with single untreated asymptomatic or minimally symptomatic brain
    metastasis by MRI.

    - Patients can have previous brain metastasis that was completely surgically resected
    if the previously resected lesion is at least 1 cm from target lesion(s) for this
    study. The location of the previous resection cavity is determined by the
    post-resection MRI.

    - Patients can have previous brain metastasis that was treated with stereotactic
    radiosurgery (SRS) if the previously treated lesion is at least 1cm from the target
    lesion(s) for this study. The location of the previous SRS treatment location is
    determined by the SRS MRI.

    - Patients can be on steroids as long as the dose has been stable for 7 days

    - No limitations on prior systemic or intrathecal therapies.

    - There are no restrictions on systemic therapy at enrollment. For further details
    regarding systemic therapy, see the "Concurrent Systemic Therapy" section in 5.0.

    - Women of childbearing potential must commit to contraceptive use while enrolled on
    the trial and continue using contraceptive for at least 7 months post study drug
    administration.

    - Life expectancy > 8 weeks

    - Laboratory criteria: normal renal function: creatinine < 1.5 x upper limit of normal
    (ULN)), liver function: bilirubin < 1.5 x ULN, transaminases < 2 x ULN, except in
    known hepatic disease, wherein may be < 5 x ULN, and blood counts: WBC 2.0,
    Neutrophils 1500, platelets 100,000, Hemoglobin 10.

    - LVEF (left ventricular ejection fraction) 50%

    - Karnofsky performance status (KPS) > 50

    - Age > 18 years

    - Patients must have the ability to give informed consent.

    - Patients must have a signed informed consent form prior to enrollment on study.

    - Negative serum pregnancy test for pre-menopausal women and women within 12 months
    from the onset of menopause.

    Exclusion Criteria:

    - No seizures, focal weakness of any extremity (by neurologic exam), or stroke symptoms
    in the past month.

    - No history of prior whole brain radiation.

    - No history of lumbar surgery or other pre-existing spinal conditions that would
    preclude frequent, safe, reliable lumbar punctures.

    - No history of serious cardiac arrhythmia or EF < 50%.

    - Systemic sites of disease need to be stable on systemic therapy based on the most
    recent (within 12 weeks) staging scans.

    - Radiation while on study is not allowed EXCEPT to a localized region for pain
    control.

    - No history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ
    of the cervix) unless the patient has been in remission and off all other cancer
    therapy for at least 3 years.

    - Patients should have no significant psychiatric illness or medical illness that would
    preclude the ability to comply with the protocol.

    - Patients may not be pregnant or breastfeeding.

    - No known hypersensitivity to trastuzumab or pertuzumab.

    - Symptomatic intrinsic lung disease or extensive tumor involvement in the lungs
    resulting in dyspnea at rest.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Safety as measured by adverse events

    Maximum tolerated dose as measure by dose limiting toxicity

    Secondary Outcome Measures

    Response rate as measured by brain MRI

    Trial Keywords

    Breast Cancer

    HER2 Positive

    HER2+

    Brain Metastases

    Metastatic Breast Cancer

    Intrathecal Treatment

    Lumbar Puncture

    Pertuzumab

    Trastuzumab

    Advanced Breast Cancer

    Duke University