The purpose of this study is to learn about the effects of the study treatment, Dendritic Cell Vaccine (DCV), in combination with trastuzumab or nivolumab to confirm the highest dose of the study treatment that can be given safely to participants with Breast Cancer (BC) with Leptomeningeal Disease (LMD).
Histologically or cytologically confirmed diagnosis of BC by ASCO/CAP guidelines (Wolff et al, 2018), or radiographically definite LMD from BC.
Trial participants must have a diagnosis of LMD. They must have the presence of malignant cells in the CSF (CSF+; note now cytology is considered diagnostic of LMD if the cytology is read as positive or suspicious; [Chamberlain et al., 2017] OR characteristic radiographic abnormalities of LMD). Signs and symptoms of LMD in and of themselves are not sufficient for inclusion.
Patients must have an ECOG performance scale of ≤2.
Proton cranial spinal RT OR cranial spinal RT using IMRT are the preferred modalities of RT to treat LMD if possible, before study. At least WBRT is required for participation.
Patients with systemic disease are eligible and will be managed as detailed in Section 7.7.5.
Pregnancy test: negative serum or urine pregnancy test at screening for women of childbearing potential. Must be repeated once a month during treatment.
Contraception: Highly effective contraception for both male and female subjects throughout the study, and for the following specified durations after the last treatment administration as follows: highly effective contraception must be used by males for at least 90 days after the last treatment administration, if the risk of conception exists, to cover the spermatogenesis Cycle, and at least 5 months after the last dose of nivolumab or 7 months after the last dose of trastuzumab for females.
The patient has an Ommaya reservoir or equivalent device that allows routine access to CSF and administration of DC1s.
Sequential
cDC1 Vaccine
Biological/VaccineAutologous peptide-pulsed cDC1 vaccine administered intrathecally.
Trastuzumab
Drug150 mg intrathecal weekly for HER2-positive participants.
Nivolumab
Drug50 mg intrathecal every 2 weeks for HER2-negative participants.
Safety Run-In: Maximum Tolerated Dose (MTD)
MTD of IT cDC1s combined with IT trastuzumab for HER2+ patients or with IT nivolumab for HER2- patients.
Phase 2: Median Overall Survival
Median survival from initiation of study treatment.
Phase 2: One-Year Survival Rate
Proportion of participants alive at one year after treatment initiation.
Progression Free Survival (PFS)
Progression-free survival is defined as the time from first study treatment (Cycle 1 Day 1) until documented disease progression or death from any cause, whichever occurs first.
Objective Response Rate (ORR)
The proportion of participants achieving an objective response during study treatment. Response in leptomeningeal/CNS disease will be assessed using Response Assessment in Neuro-Oncology Leptomeningeal Metastases (RANO-LM) criteria, and response in non-CNS/systemic disease will be assessed using RECIST version 1.1 criteria.
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H. Lee Moffitt Cancer Center and Research Institute
Lead sponsor
United States Department of Defense
Collaborator
