NCT04588545
Radiation Therapy Followed by Intrathecal Trastuzumab/Pertuzumab in HER2+ Breast Leptomeningeal Disease
Active, Not Recruiting
PHASE1Ages 18+InterventionalTreatmentH. Lee Moffitt Cancer Center and Research InstituteInvestigator-initiated
~33 participants
Updated 2026-05-26 on ClinicalTrials.gov
What's tested:Radiation TherapyPertuzumabTrastuzumab
At a glance
Recruiting sites
0 of 2 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Phase 1: Maximum Tolerated Dose (MTD) of Intrathecal (IT) pertuzumab in combination with IT trastuzumab
Measured over Up to 12 weeks per dosing cohort
+1 more outcome measured
Conditions
Where it's being run
2 sites across 2 statesFlorida1
Illinois1
Study leadership
- Kamran Ahmed, MD · PRINCIPAL_INVESTIGATOR · Moffitt Cancer Center
Who to contact
This trial hasn't published a contact. View it on ClinicalTrials.gov
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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.
Exclusion
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
What this trial measures
- Phase 1: Maximum Tolerated Dose (MTD) of Intrathecal (IT) pertuzumab in combination with IT trastuzumabUp 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.
- Phase 2: Overall Survival (OS)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.