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
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.
Description
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.
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
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…
Interventions
- RadiationRadiation 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.
- DrugPertuzumab
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).
- DrugTrastuzumab
Participants will be treated at a fixed dose of 80 mg trastuzumab.
Locations (2)
- Moffitt Cancer CenterTampa, Florida
- Northwestern UniversityEvanston, Illinois