BATs in Patients With Breast Cancer and Leptomeningeal Metastases

NCT03661424 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 20805
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Breast Cancer Female; Leptomeningeal Metastases

Keywords

Metastatic Breast Cancer; Adoptive Cell Therapy; Armed Activated T-cells; Bispecific Antibodies; Immunotherapy

Outcome Measures

Primary Outcomes (7)

• Types of adverse events (AEs)

  Types of any adverse events or abnormalities of laboratory tests

  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

  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

  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

  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

  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

  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.

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

Secondary Outcomes (11)

• Immune shift: in vitro cytotoxicity assays and/or IFN-y EliSpots against breast cancer cell lines

  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

  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

  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

  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

  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

Study Arms (1)

Test dose then 8 doses HER2 Bi-armed activated T-cells (BATs)

EXPERIMENTAL

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

Interventions

HER2 BATs DRUG

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.

Test dose then 8 doses HER2 Bi-armed activated T-cells (BATs)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Related Publications (2)

• 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.

  PMID: 25688159 BACKGROUND

• 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.

  PMID: 25802762 BACKGROUND

MeSH Terms

Conditions

Meningeal Carcinomatosis; Breast Neoplasms

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Camilo Fadul, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 22, 2018
• First Posted: September 7, 2018
• Study Start: February 26, 2019
• Primary Completion: December 14, 2021
• Study Completion: December 14, 2021
• Last Updated: December 20, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)