Radiation Therapy Followed by Intrathecal Trastuzumab/Pertuzumab in HER2+ Breast Leptomeningeal Disease
NCT ID: NCT04588545
Last Updated: 2025-11-14
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
39 participants
INTERVENTIONAL
2020-12-10
2026-08-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Radiation Therapy followed by 10 mg Pertuzumab and 80 mg Trastuzumab
Treatment will be initiated with radiation therapy (RT), either whole brain radiation therapy or focal brain/spine radiation therapy. Participants will be treated at dose level 1 of 4 with 10 mg pertuzumab along with 80 mg trastuzumab via Ommaya reservoir over 2-5 minutes. Pertuzumab and trastuzumab will be administered sequentially. Participants will be observed 30 to 60 minutes before commencing the next agent. Participants will be treated twice a week for 4 weeks, once a week for 4 weeks, and then once every 2 weeks.
Radiation Therapy
Participants will receive radiation therapy (RT), either whole brain radiation therapy or focal brain/spine RT. The goal of RT is to palliate symptoms and improve the flow of Intrathecal (IT) therapy through the cerebrospinal fluid (CSF). As such, various RT schedules and targets are permitted. It is expected that the majority of patients will receive WBRT with 30 Gy in 10 fractions. However, shorter fractions of 20 Gy in 5 fractions of WBRT are permitted. In those patients who have more localized leptomeningeal disease in the spine, focal RT in up to 10 fractions may be administered with the exact dose left up to the discretion of the treating radiation oncologist.
Pertuzumab
Participants will be treated at 1 of 4 dose levels of pertuzumab, beginning at 10 mg and increasing up to 80 mg or Maximum Tolerated Dose (MTD).
Trastuzumab
Participants will be treated at a fixed dose of 80 mg trastuzumab.
Radiation Therapy followed by 20 mg Pertuzumab and 80 mg Trastuzumab
Treatment will be initiated with radiation therapy (RT), either whole brain radiation therapy or focal brain/spine radiation therapy. Participants will be treated at dose level 2 of 4 with 20 mg pertuzumab along with 80 mg trastuzumab via Ommaya reservoir over 2-5 minutes. Pertuzumab and trastuzumab will be administered sequentially. Participants will be observed 30 to 60 minutes before commencing the next agent. Participants will be treated twice a week for 4 weeks, once a week for 4 weeks, and then once every 2 weeks.
Radiation Therapy
Participants will receive radiation therapy (RT), either whole brain radiation therapy or focal brain/spine RT. The goal of RT is to palliate symptoms and improve the flow of Intrathecal (IT) therapy through the cerebrospinal fluid (CSF). As such, various RT schedules and targets are permitted. It is expected that the majority of patients will receive WBRT with 30 Gy in 10 fractions. However, shorter fractions of 20 Gy in 5 fractions of WBRT are permitted. In those patients who have more localized leptomeningeal disease in the spine, focal RT in up to 10 fractions may be administered with the exact dose left up to the discretion of the treating radiation oncologist.
Pertuzumab
Participants will be treated at 1 of 4 dose levels of pertuzumab, beginning at 10 mg and increasing up to 80 mg or Maximum Tolerated Dose (MTD).
Trastuzumab
Participants will be treated at a fixed dose of 80 mg trastuzumab.
Radiation Therapy followed by 40 mg Pertuzumab and 80 mg Trastuzumab
Treatment will be initiated with radiation therapy (RT), either whole brain radiation therapy or focal brain/spine radiation therapy. Participants will be treated at dose level 3 of 4 with 40 mg pertuzumab along with 80 mg trastuzumab via Ommaya reservoir over 2-5 minutes. Pertuzumab and trastuzumab will be administered sequentially. Participants will be observed 30 to 60 minutes before commencing the next agent. Participants will be treated twice a week for 4 weeks, once a week for 4 weeks, and then once every 2 weeks.
Radiation Therapy
Participants will receive radiation therapy (RT), either whole brain radiation therapy or focal brain/spine RT. The goal of RT is to palliate symptoms and improve the flow of Intrathecal (IT) therapy through the cerebrospinal fluid (CSF). As such, various RT schedules and targets are permitted. It is expected that the majority of patients will receive WBRT with 30 Gy in 10 fractions. However, shorter fractions of 20 Gy in 5 fractions of WBRT are permitted. In those patients who have more localized leptomeningeal disease in the spine, focal RT in up to 10 fractions may be administered with the exact dose left up to the discretion of the treating radiation oncologist.
Pertuzumab
Participants will be treated at 1 of 4 dose levels of pertuzumab, beginning at 10 mg and increasing up to 80 mg or Maximum Tolerated Dose (MTD).
Trastuzumab
Participants will be treated at a fixed dose of 80 mg trastuzumab.
Radiation Therapy followed by 80 mg Pertuzumab and 80 mg Trastuzumab
Treatment will be initiated with radiation therapy (RT), either whole brain radiation therapy or focal brain/spine radiation therapy. Participants will be treated at dose level 4 of 4 with 80 mg pertuzumab along with 80 mg trastuzumab via Ommaya reservoir over 2-5 minutes. Pertuzumab and trastuzumab will be administered sequentially. Participants will be observed 30 to 60 minutes before commencing the next agent. Participants will be treated twice a week for 4 weeks, once a week for 4 weeks, and then once every 2 weeks.
Radiation Therapy
Participants will receive radiation therapy (RT), either whole brain radiation therapy or focal brain/spine RT. The goal of RT is to palliate symptoms and improve the flow of Intrathecal (IT) therapy through the cerebrospinal fluid (CSF). As such, various RT schedules and targets are permitted. It is expected that the majority of patients will receive WBRT with 30 Gy in 10 fractions. However, shorter fractions of 20 Gy in 5 fractions of WBRT are permitted. In those patients who have more localized leptomeningeal disease in the spine, focal RT in up to 10 fractions may be administered with the exact dose left up to the discretion of the treating radiation oncologist.
Pertuzumab
Participants will be treated at 1 of 4 dose levels of pertuzumab, beginning at 10 mg and increasing up to 80 mg or Maximum Tolerated Dose (MTD).
Trastuzumab
Participants will be treated at a fixed dose of 80 mg trastuzumab.
Interventions
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Radiation Therapy
Participants will receive radiation therapy (RT), either whole brain radiation therapy or focal brain/spine RT. The goal of RT is to palliate symptoms and improve the flow of Intrathecal (IT) therapy through the cerebrospinal fluid (CSF). As such, various RT schedules and targets are permitted. It is expected that the majority of patients will receive WBRT with 30 Gy in 10 fractions. However, shorter fractions of 20 Gy in 5 fractions of WBRT are permitted. In those patients who have more localized leptomeningeal disease in the spine, focal RT in up to 10 fractions may be administered with the exact dose left up to the discretion of the treating radiation oncologist.
Pertuzumab
Participants will be treated at 1 of 4 dose levels of pertuzumab, beginning at 10 mg and increasing up to 80 mg or Maximum Tolerated Dose (MTD).
Trastuzumab
Participants will be treated at a fixed dose of 80 mg trastuzumab.
Eligibility Criteria
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Inclusion Criteria
And/or patients with HER2 positive cells in the cerebral spinal fluid.
* Participants may have concomitant brain metastases
* Cerebrospinal fluid (CSF) sampling is required to document LMD if not documented by MRI. Participants are still eligible CSF is negative but LMD disease is documented on MRI
* Life expectancy greater than 8 weeks
* Consent to pretreatment tumor biopsy or retrieval of archival tissue
* Normal renal (creatinine \<1.5 × upper limit of normal \[ULN\]), liver (bilirubin \< 1.5 × ULN, transaminases \<3.0 × ULN, except in known hepatic disease, wherein may be \<5 × ULN) and blood counts (white blood cells ≥2.5, neutrophils ≥1000, platelets ≥75,000, hemoglobin ≥8)
* LVEF \>50%
* KPS \>/= 60
* Patients with surgery within 14 days should have recovered from all effects of the surgery and be cleared by their surgeon
* There is no limit on prior systemic or IT therapies
* Must be willing to have an Ommaya reservoir placed and a candidate for an Ommaya reservoir placement
* Women of childbearing potential and sexually active males must commit to the use of effective contraception while on study. Contraception methods should start a minimum of 14 days before the first administration of study drug and continue for the duration of study treatment and for at least 7 months after the last dose of study treatment.
* Ability to sign informed consent.
* Patients may continue treatment with IV trastuzumab, pertuzumab, or other HER2-directed, hormonal, or chemotherapeutic agents if controlling systemic disease and leptomeningeal metastases that developed while on these therapies. In addition, at time of systemic progression, patients may start additional agents at the discretion of the treating physician according to criteria per protocol.
Exclusion Criteria
* Cannot be on systemic agents (chemotherapy) that have Central Nervous System (CNS) penetration (temozolomide, carmustine, lomustine, etoposide, capecitabine, carboplatin, vinorelbine, bevacizumab, irinotecan, and topotecan) unless they develop or have progressive or persistent leptomeningeal metastases while on these agent(s). See protocol for additional information regarding systemic therapies.
* Major surgery or significant traumatic injury that has not been recovered from 14 days before the initiation of study drug
* Symptomatic lung disease resulting in shortness of breath at rest
* Women who are pregnant or breastfeeding
* History of serious adverse event to any of the study drugs or study drug components
* Whole Body Radiation Therapy (WBRT) is not allowed while patients receive IT trastuzumab/pertuzumab; however, focal stereotactic or palliative RT is allowed
* Significant medical or psychiatric illness that would interfere with compliance and ability to tolerate treatment as outlined in the protocol
18 Years
ALL
No
Sponsors
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Genentech, Inc.
INDUSTRY
H. Lee Moffitt Cancer Center and Research Institute
OTHER
Responsible Party
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Principal Investigators
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Kamran Ahmed, MD
Role: PRINCIPAL_INVESTIGATOR
Moffitt Cancer Center
Locations
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Moffitt Cancer Center
Tampa, Florida, United States
Northwestern University
Evanston, Illinois, United States
Countries
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Central Contacts
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Facility Contacts
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Priya Kumthekar, MD
Role: primary
Related Links
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Moffitt Cancer Center's Clinical Trials Website
Other Identifiers
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ML41590
Identifier Type: OTHER
Identifier Source: secondary_id
MCC-20487
Identifier Type: -
Identifier Source: org_study_id