RECRUITING

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

Conditions

HER2-positive Breast Cancer Leptomeningeal Metastasis Leptomeningeal Disease

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2020-12-10

Study Completion:2025-07-29

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04588545

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. * 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.	* 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

Inclusion Criteria

Exclusion 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.
* 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.

* 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

Contacts and Locations

Study Contact

Kamran Ahmed, MD

CONTACT

813-745-8424

kamran.ahmed@moffitt.org

Principal Investigator

Kamran Ahmed, MD

PRINCIPAL_INVESTIGATOR

Moffitt Cancer Center

Study Locations (Sites)

Moffitt Cancer Center

Tampa, Florida, 33612

United States

Northwestern University

Evanston, Illinois, 60208

United States

Collaborators and Investigators

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Kamran Ahmed, MD, PRINCIPAL_INVESTIGATOR, Moffitt Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-12-10

Study Completion Date2025-07-29

Study Record Updates

Study Start Date2020-12-10

Study Completion Date2025-07-29

Terms related to this study

Additional Relevant MeSH Terms

HER2-positive Breast Cancer
Leptomeningeal Metastasis
Leptomeningeal Disease