Breast Cancer, Leptomeningeal Disease
Conditions
Brief summary
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).
Interventions
BIOLOGICALcDC1 Vaccine
Autologous peptide-pulsed cDC1 vaccine administered intrathecally.
DRUGTrastuzumab
150 mg intrathecal weekly for HER2-positive participants.
DRUGNivolumab
50 mg intrathecal every 2 weeks for HER2-negative participants.
Sponsors
H. Lee Moffitt Cancer Center and Research Institute
United States Department of Defense
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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. * Coincident brain or spinal cord metastases are allowed if these are stable and do not require local therapy at the time of enrollment. Individuals with previously treated stable brain metastases are eligible to participate. * Stereotactic radiosurgery (SRS) and/or prior radiotherapy is permitted ≥2 weeks before the initial dendritic cell (DC) vaccine dose. A follow-up brain MRI should be obtained before the DC vaccine to determine the stability of the lesions. An interval of at least 2 weeks after the end of brain radiation or surgical resection of brain lesions or cytotoxic, targeted, immune, or investigational agent is required. * Must be ≥18 years of age on the day of signing the consent. * Life expectancy of ≥8 weeks. * Demonstrate adequate organ function as defined in Table 5. All screening labs should be performed within 14 days of treatment initiation. * Ability to understand and the willingness to sign a written informed consent document. * Corticosteroids at doses equivalent to ≤4 mg of dexamethasone daily or equivalent for symptom control are acceptable. This should be minimized when possible. * If the disease has progressed on current treatment before consent, patients may continue current systemic cancer therapies by PI discretion see Section 7.7.5 (Systemic Therapies Allowed) and Section 5.2, 1 and 2 (
Exclusion criteria
). * 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. * Patient must be able to tolerate MRIs of brain with contrast for routine disease assessments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Run-In: Maximum Tolerated Dose (MTD) | Up to 28 days | MTD of IT cDC1s combined with IT trastuzumab for HER2+ patients or with IT nivolumab for HER2- patients. |
| Phase 2: Median Overall Survival | Up to 1 year | Median survival from initiation of study treatment. |
| Phase 2: One-Year Survival Rate | Up to 1 year | Proportion of participants alive at one year after treatment initiation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Up to 1 year | 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) | Up to 1 Year | 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. |
Countries
United States
Contacts
CONTACTJulianne Hardesty
PRINCIPAL_INVESTIGATORPeter Forsyth, MD
Moffitt Cancer Center
Outcome results
None listed