Radiation Therapy Followed by Intrathecal Trastuzumab/Pertuzumab in HER2+ Breast Leptomeningeal Disease
Phase I/II Study of Radiation Therapy Followed by Intrathecal Trastuzumab/Pertuzumab in the Management of HER2+ Breast Leptomeningeal Disease
H. Lee Moffitt Cancer Center and Research Institute
39 participants
Dec 10, 2020
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria15
- 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 Criteria8
- 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
Interventions
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.
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).
Participants will be treated at a fixed dose of 80 mg trastuzumab.
Locations(2)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT04588545