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NCT Number: NCT04588545

Radiation Therapy Followed by Intrathecal Trastuzumab/Pertuzumab in HER2+ Breast Leptomeningeal Disease

The purpose of this study is to find out if radiation therapy followed by intrathecal trastuzumab and pertuzumab is safe and will result in improved survival in HER2 positive breast cancer which has metastasized to the leptomeninges.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

HER2-positive Breast Cancer Central Nervous System Neoplasms Leptomeningeal Disease Leptomeningeal Metastasis Meningeal Carcinomatosis Meningeal Neoplasms Neoplasms Neoplasms by Site Nervous System Diseases Nervous System Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Moffitt Cancer Center, Tampa, Florida, United States

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About this study

The study is designed as a prospective, single-arm, nonrandomized, open-label, phase I/II trial of radiation therapy (RT) followed by intrathecal (IT) trastuzumab/pertuzumab in the management of HER2+ breast leptomeningeal disease (LMD). Treatment will be initiated with RT, whole brain RT (WBRT) and/or focal brain/spine RT followed by IT trastuzumab/pertuzumab.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Confirmation of HER2 positivity. All patients with HER2+ cancers will be allowed to enroll if they have leptomeningeal disease (LMD). Patients may be IHC 3+ and/or FISH-positive. IHC 2+ HER2 patients are eligible with reflex FISH-positive testing with the ratio ≥2.0.

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

  • Current or prior participation in a study of an investigational agent or investigational device within 2 weeks of the first dose of study treatment
  • 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

Treatment and study plan

radiation therapy

Radiation

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

Drug

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

Drug

Participants will be treated at a fixed dose of 80 mg trastuzumab.

Primary outcomes

  1. Phase 1: Maximum Tolerated Dose (MTD) of Intrathecal (IT) pertuzumab in combination with IT trastuzumab

    Time frame: Up to 12 weeks per dosing cohort

    MTD will be determined by testing increasing doses or pertuzumab beginning at 10 mg increasing to 20 mg, 40 mg and 80 mg, along with a fixed dose of 80 mg Trastuzumab.

  2. Phase 2: Overall Survival (OS)

    Time frame: 1 year after study enrollment

    1 year Overall Survival (OS), defined as the time between the date of study enrollment and the date of death due to any cause.

Secondary outcomes

  1. Response Rate

    Time frame: Up to 1 year

    All patients included in the study will be assessed for response to treatment. Each patient will be assigned one of the following categories: 1) Complete Response,2) Partial Response, 3) Stable Disease, 4) Progressive Disease, 5) Early death due to disease, 6) Early death due to toxicity 7)Early death due to unknown cause. Participants in categories 4 through 6 would be considered as failing to respond to treatment.

  2. Progression Free Survival (PFS)

    Time frame: Up to 1 year

    PFS measured from the date of first treatment to the date of first observation of Progressive Disease (PD), nonreversible neurologic progression, or death due to any cause

Sponsors and collaborators

Lead sponsor

H. Lee Moffitt Cancer Center and Research Institute

Other

Collaborators

  • Genentech, Inc.

Registry information

Official study title

Phase I/II Study of Radiation Therapy Followed by Intrathecal Trastuzumab/Pertuzumab in the Management of HER2+ Breast Leptomeningeal Disease

Important dates

Study start
2020
Primary completion
2027
Study completion
2027
First posted
Oct 19, 2020
Registry last updated
May 26, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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