A Phase 1 interventional study of HER2 BATs in Breast Cancer Female and Leptomeningeal Metastases, sponsored by University of Virginia. Terminated at 1 site in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-12-20.
Sponsored by University of Virginia · Phase 1, Interventional, and Treatment
This study uses bi-specific antibody (HER2Bi) armed activated T-cells (HER2 BATs) to target breast cancer cells that have metastasized to the membranes surrounding the brain and spinal cord. This is known as leptomeningeal metastases. Two doses will be evaluated in order to determine a safe dose.
Study treatment includes a test dose of HER2 BATs followed by 8 weekly infusions of HER2 BATs at the assigned dose level. Before, during and after study treatment, participants will be monitored objectively by brain MRIs and clinically through physical and neurological exams, and blood and cerebrospinal fluid will be collected to evaluate immune responses.
Once subjects are determined eligible, white blood cells (lymphocytes) are collected via leukapheresis procedure approximately 3 to 4 weeks prior to the first BATs infusion. The white blood cells, specifically T cells, are then mixed with two proteins in order to activate the cells to multiply.
After approximately 14 days in culture, the activated T cells are coated with OKT3 and trastuzumab/Herceptin (HER2Bi), and washed to remove excess Herceptin in order to produce bispecific antibody armed T cells (BATs). Cells are then frozen and stored until scheduled to be infused.
Up to 2 weeks following leukapheresis, participants will undergo surgery to place the catheter/reservoir into the lateral ventricle of the brain to allow intraventricular administration of HER2 BATs and a chemotherapy agent methotrexate. A few weeks later, participants will receive the intraventricular methotrexate in order to control disease while the BATs product is being manufactured. About 4-5 weeks following the leukapheresis and at least 7 days after receiving methotrexate, study treatment will begin with a test dose of HER2 BATs. If this dose is well tolerated by the participant, she will then receive 8 weekly doses of HER2 BATs at the assigned dose level.
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's enrollment of 3 is below the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →University of Virginia is the lead sponsor of 653 studies on the registry; 134 are open to participants now.
Of its 60 completed or terminated interventional studies of FDA-regulated products, 41 (68%) have results posted.
Counted across the registry records on this site, refreshed daily.
Absolute lymphocyte count ≥ 500/mm3 Absolute neutrophil count ≥ 1000/mcL Platelets ≥ 100,000 / mnL Hemoglobin ≥ 8 g/dL BUN ≤ 1.5 x upper limit of normal (ULN) Serum creatinine within the normal limits OR measured or calculated creatinine clearance ≥ 60 mL/min 1.73m2 Serum total bilirubin ≤ 2 x ULN OR AST (SGOT) and ALT (SGPT) ≤ 5 x ULN Albumin ≥ 2.5 mg/dL
Exclusion Criteria:
Approximately 4 weeks following registration and blood collection, participants are given a test dose of HER2 BATs followed by 8 weekly infusions. Infusions are given intraventricularly.
Drug: HER2 BATs
A test dose (1 million cells) of HER2 BATs (at one of the two dose levels: 5 million cells or 10 million cells per infusion) followed by 8 weekly infusions of Her2 BATs delivered into the ventricle of the brain. Infusions are delivered weekly over 8 weeks with brain MRIs prior to first infusion and following the eighth infusion. Blood will be drawn for immune evaluation before during and after study treatment.
Types of adverse events (AEs)
Types of any adverse events or abnormalities of laboratory tests
Time frame: For each participant, AEs will be collected from the time of the first protocol-related procedure through 30 days following last infusion of BATs. SAEs considered related to study treatment will also be collected following this period.
Frequency of adverse events (AEs)
Frequency of any adverse events or abnormalities of laboratory tests
Time frame: For each participant, AEs will be collected from the time of the first protocol-related procedure through 30 days following last infusion of BATs. SAEs considered related to study treatment will also be collected following this period.
Severity of adverse events (AEs)
Severity of any adverse events or abnormalities of laboratory tests
Time frame: For each participant, AEs will be collected from the time of the first protocol-related procedure through 30 days following last infusion of BATs. SAEs considered related to study treatment will also be collected following this period.
Timing of onset of adverse events
Timing of onset of any adverse events or abnormalities of laboratory tests
Time frame: For each participant, AEs will be collected from the time of the first protocol-related procedure through 30 days following last infusion of BATs. SAEs considered related to study treatment will also be collected following this period.
Duration of adverse events
Duration of any adverse events or abnormalities of laboratory tests
Time frame: For each participant, AEs will be collected from the time of the first protocol-related procedure through 30 days following last infusion of BATs. SAEs considered related to study treatment will also be collected following this period.
Relationship to study therapy of any adverse events or abnormalities of laboratory tests as determined by CTCAE v5.0 will be assessed based on protocol-defined relationships of definitely, probably, possibly, unlikely and unrelated to study therapy.
Relationship to study therapy of any adverse events or abnormalities of laboratory tests
Time frame: For each participant, AEs will be collected from the time of the first protocol-related procedure through 30 days following last infusion of BATs. SAEs considered related to study treatment will also be collected following this period.
Number of participants achieving at least 80% of the planned HER2 BATs dose.
If at least 80% of the planned dose of cells cannot be produced for 3 consecutive participants at a designated dose level, that dose level will be considered not feasible.
Time frame: An average of 4 weeks following blood draw to collect cells for HER2 BATs
Immune shift: in vitro cytotoxicity assays and/or IFN-y EliSpots against breast cancer cell lines
Immune shift induced by Her2 BATs as detected by in vitro cytotoxicity assays and/or IFN-γ EliSpots against breast cancer cell lines
Time frame: Blood for immune analysis collected prior to, during and following study treatment (tx) (up to 6 months following study tx).
Immune shift: Phenotyping of activating and regulatory immune cells
Immune shift induced by Her2 BATs as detected by phenotyping of activating and regulatory immune cells
Time frame: Blood for immune analysis collected prior to, during and following study treatment (tx) (up to 6 months following study tx).
Immune shift: Measurement of cytokine patterns
Immune shift induced by Her2 BATs as detected by measurement of cytokine patterns
Time frame: Blood for immune analysis collected prior to, during and following study treatment (tx) (up to 6 months following study tx).
Immune shift: Determination of anti-Her2 antibodies
Immune shift induced by Her2 BATs as detected by determination of anti-Her2 antibodies
Time frame: Blood for immune analysis collected prior to, during and following study treatment (tx) (up to 6 months following study tx).
Correlation of clinical and immune response characteristics to progression-free survival
Correlation individually and by heatmap analysis of imaging, pathology, clinical, and immune response characteristics to progression free survival (PFS)
Time frame: Blood collected prior to, during and following study treatment (tx) (up to 6 months following study tx). Clinical characteristics and imaging prior to and after study tx through 1st progression
Correlation of clinical and immune response characteristics to overall survival
Correlation individually and by heatmap analysis of imaging, pathology, clinical, and immune response characteristics to overall survival (OS).
Time frame: Blood for immune analysis collected prior to, during and after study treatment (tx) (up to 6 months following study tx). Clinical characteristics and imaging prior to and after study tx through 1st progression
Objective response rate (ORR)
Proportion of participants with complete or partial response according to brain and spine MRI
Time frame: Assessed on MRI studies done 9 weeks after first BATs infusion
Progression-free survival (PFS)
Length of time from study participation initiation through disease progression for each participant
Time frame: From date of first BATs infusion (approximately 4 weeks following eligibility confirmation) until the date of confirmed progression, assessed up to 28 months
Overall survival (OS)
Length of time from study participation initiation through death or for 2 years following study treatment for each participant
Time frame: Through each participant's death or for 2 years following study treatment
MD Anderson Symptom Inventory for Spinal Tumors (MDASI - SP)
The MDASI- SP is a 24 item questionnaire that focuses on symptoms related to spinal tumors. For each potential symptom, there is an eleven-point scale where 0 is "Not Present" and 10 is "As Bad As You Can Imagine" so the minimum score would be 0 and the maximum score would be 240. For a subset of questions, the scale measures how much the symptoms interfered with other parts of life and the scale ranges from symptoms that "Did Not Interfere" (0) to those that "Interfered Completely" (10). Lower scores indicate fewer/less severe/less interfering symptoms and higher scores indicate more/more severe/more interfering symptoms.
Time frame: Prior to test dose of study treatment, prior to the 5th and 8th weekly infusions, and 30 days following last infusion
MD Anderson Symptom Inventory for Brain Tumors (MDASI- BT)
The MDASI- BT is a 28 item questionnaire that focuses on symptoms related to brain tumors. For each potential symptom, there is an eleven-point scale where 0 is "Not Present" and 10 is "As Bad As You Can Imagine" so the minimum score would be 0 and the maximum score would be 280. For a subset of questions, the scale measures how much the symptoms interfered with other parts of life and the scale ranges from symptoms that "Did Not Interfere" (0) to those that "Interfered Completely" (10). Lower scores indicate fewer/less severe/less interfering symptoms and higher scores indicate more/more severe/more interfering symptoms.
Time frame: Prior to test dose of study treatment, prior to the 5th and 8th weekly infusions, and 30 days following last infusion
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