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Breast Cancer FemalePhase 1NCT03661424

BATs in Patients With Breast Cancer and Leptomeningeal Metastases

A Phase 1 study testing HER2 BATs in people with Breast Cancer Female and Leptomeningeal Metastases, run by University of Virginia at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
HER2 BATs
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
26 Feb 2019to 14 Dec 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Be willing and able to provide written informed consent for the trial.
  • Participants must be female.
  • Histologically confirmed breast cancer (any Her2, estrogen receptor (ER), or progesterone receptor (PR) expression) with leptomeningeal metastasis (LM) as determined by imaging and/or cerebrospinal fluid (CSF) cytology.
  • 18 years of age or older.
  • Women of reproductive potential must agree to use an effective method of contraception during therapy. Effective methods include intrauterine device (IUD), vasectomy of the male partner, diaphragm with spermicide, cervical cap with spermicide, contraceptive sponge, male or female condom, or hormonal contraceptive.
  • Karnofsky Performance Status (KPS) of ≥60.
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  • Eligible for intraventricular (IVENT) catheter/reservoir placement as determined by neurosurgery.
  • Demonstrate adequate organ function as defined below. All screening labs should be performed within 10 days of confirmation of eligibility.
  • 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

Who cannot join

  • Current severe increased intracranial pressure with clinical or imaging findings suggestive of herniation, status epilepticus, or other serious complications requiring emergency or urgent intervention.
  • Patients who cannot have MRI studies for any reason (intolerance, medical contraindication, etc.).
  • Patients with a history of another malignancy within 1 year of study enrollment with the following exceptions: patients with history of ductal carcinoma in situ (DCIS), squamous cell skin cancers, or other in situ carcinomas are not excluded.
  • Patients with unresolved autoimmune toxicity.
  • Patients with a known disorder that increases the risk of bleeding (e.g., Hemophilia, von Willebrands disease, or clinically significant clotting factor deficiency).
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
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  • Administration of any investigational agents, immunomodulating agents, radiation therapy or chemotherapy for MBC within the 7 days before the 80 mL blood draw to collect cells for study treatment.
  • Has Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) or known active Hepatitis B (e.g. HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Pregnancy or lactation at the time of registration.
  • Psychiatric or addictive disorders or other conditions that in the opinion of the investigator would preclude the patient from complying with the study protocol.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Virginia

    Charlottesville, Virginia, 22908

Other trials in United States

About this study

Official title: A Phase I Study of Anti-CD3 x Anti-Her2/Neu (Her2Bi) Armed Activated T Cells (ATC) in Patients With Breast Cancer Leptomeningeal Metastases

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.

Read the detailed description

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.

Being tested
HER2 BATs
Keywords
Metastatic Breast Cancer, Adoptive Cell Therapy, Armed Activated T-cells, Bispecific Antibodies, Immunotherapy
Medical subject headings
Meningeal Carcinomatosis, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HER2 BATsDrug

    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.

Study groups in NCT03661424
Study groupRoleWhat they receive
Test dose then 8 doses HER2 Bi-armed activated T-cells (BATs)ExperimentalApproximately 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.
Receives: Drug: HER2 BATs

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Types of adverse events (AEs)

    Types of any adverse events or abnormalities of laboratory tests

    Measured: 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.

  2. Frequency of adverse events (AEs)

    Frequency of any adverse events or abnormalities of laboratory tests

    Measured: 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.

  3. Severity of adverse events (AEs)

    Severity of any adverse events or abnormalities of laboratory tests

    Measured: 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.

  4. Timing of onset of adverse events

    Timing of onset of any adverse events or abnormalities of laboratory tests

    Measured: 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.

  5. Duration of adverse events

    Duration of any adverse events or abnormalities of laboratory tests

    Measured: 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.

  6. 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

    Measured: 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.

  7. 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.

    Measured: An average of 4 weeks following blood draw to collect cells for HER2 BATs

Secondary outcomes (11)
  1. 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

    Measured: Blood for immune analysis collected prior to, during and following study treatment (tx) (up to 6 months following study tx).

  2. 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

    Measured: Blood for immune analysis collected prior to, during and following study treatment (tx) (up to 6 months following study tx).

  3. Immune shift: Measurement of cytokine patterns

    Immune shift induced by Her2 BATs as detected by measurement of cytokine patterns

    Measured: Blood for immune analysis collected prior to, during and following study treatment (tx) (up to 6 months following study tx).

  4. Immune shift: Determination of anti-Her2 antibodies

    Immune shift induced by Her2 BATs as detected by determination of anti-Her2 antibodies

    Measured: Blood for immune analysis collected prior to, during and following study treatment (tx) (up to 6 months following study tx).

  5. 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)

    Measured: 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

  6. 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).

    Measured: 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

  7. Objective response rate (ORR)

    Proportion of participants with complete or partial response according to brain and spine MRI

    Measured: Assessed on MRI studies done 9 weeks after first BATs infusion

  8. Progression-free survival (PFS)

    Length of time from study participation initiation through disease progression for each participant

    Measured: From date of first BATs infusion (approximately 4 weeks following eligibility confirmation) until the date of confirmed progression, assessed up to 28 months

  9. Overall survival (OS)

    Length of time from study participation initiation through death or for 2 years following study treatment for each participant

    Measured: Through each participant's death or for 2 years following study treatment

  10. 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.

    Measured: Prior to test dose of study treatment, prior to the 5th and 8th weekly infusions, and 30 days following last infusion

  11. 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.

    Measured: Prior to test dose of study treatment, prior to the 5th and 8th weekly infusions, and 30 days following last infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Sep 2018
  2. Study start26 Feb 2019
  3. Primary completion14 Dec 2021
  4. Study completion14 Dec 2021

Why it stopped: slow study accrual, partially due to pandemic

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03661424
Sponsor's protocol ID
20805
Status last verified
Dec 2022
First submitted
22 Aug 2018
Last updated
20 Dec 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Lum LG, Thakur A, Al-Kadhimi Z, Colvin GA, Cummings FJ, Legare RD, Dizon DS, Kouttab N, Maizel A, Colaiace W, Liu Q, Rathore R. Targeted T-cell Therapy in Stage IV Breast Cancer: A Phase I Clinical Trial. Clin Cancer Res. 2015 May 15;21(10):2305-14. doi: 10.1158/1078-0432.CCR-14-2280. Epub 2015 Feb 16.

    PubMed 25688159
  • Vaishampayan U, Thakur A, Rathore R, Kouttab N, Lum LG. Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients. Prostate Cancer. 2015;2015:285193. doi: 10.1155/2015/285193. Epub 2015 Feb 23.

    PubMed 25802762

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing HER2 BATs in people with Breast Cancer Female and Leptomeningeal Metastases, run by University of Virginia at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 20 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: slow study accrual, partially due to pandemic). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Types of adverse events (AEs) (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.). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03661424, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2022.

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