HER2-CAR T Cells in Treating Patients With Recurrent Brain or Leptomeningeal Metastases

NCT03696030 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 17237NCI-2018-01270
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of HER2-CAR T cells in treating patients with cancer that has spread to the brain or leptomeninges and has come back (recurrent). HER2-CAR T cells delivered into the ventricles of the brain may recognize and kill tumor cells.

Conditions

Malignant Neoplasm; Metastatic Malignant Neoplasm in the Brain; Breast Cancer; Metastatic Malignant Neoplasm in the Leptomeninges; HER2-positive Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Incidence of dose limiting toxicities (DLTs)

  Rate and associated 90% Clopper and Pearson binomial confidence limits (90% CI) will be estimated for participants' experiencing DLTs at the recommended phase 2 dose schedule.

  21 days post T cell infusion

• Number of participants with treatment related adverse events

  Will be as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. Tables will be created to summarize all toxicities and side effects by dose, time post treatment, organ, severity and arm.

  Up to 15 years

Secondary Outcomes (17)

• HER2-CAR T cells cerebrospinal fluid (CSF) and peripheral blood

  Measured over time from baseline through 1 year, the number of measurements is determined by whether or not the participant has progressed (progressed: baseline, 1, 3, 6, and 12 months, not progressed: baseline, 1, 3, 6, 8,10 and 12 months)

• Endogenous B cells in CSF and peripheral blood

  Measured over time from baseline through 1 year, the number of measurements is determined by whether or not the participant has progressed (progressed: baseline, 1, 3, 6, and 12 months, not progressed: baseline, 1, 3, 6, 8,10 and 12 months)

• T cells in CSF and peripheral blood

  Progressed: baseline, 1, 3, 6, and 12 months, not progressed: baseline, 1, 3, 6, 8,10 and 12 months)

• Myeloid cells in CSF and peripheral blood

  Measured over time from baseline through 1 year, the number of measurements is determined by whether or not the participant has progressed (progressed: baseline, 1, 3, 6, and 12 months, not progressed: baseline, 1, 3, 6, 8,10 and 12 months)

• Host immune subsets (e.g. T cell inhibitory/exhaustion markers, activation markers, and effector memory T cells) in CSF and peripheral blood

  Measured over time from baseline through 1 year, the number of measurements is determined by whether or not the participant has progressed (progressed: baseline, 1, 3, 6, and 12 months, not progressed: baseline, 1, 3, 6, 8,10 and 12 months)

Study Arms (2)

Treatment (HER2-CAR T cells) - TCM Central Memory T cell

EXPERIMENTAL

Patients receive HER2-CAR T cells (TCM Central Memory T cell) via intraventricular administration over 5 minutes once weekly for 3 doses in the absence of disease progression or unacceptable toxicity. If patients continue to meet all eligibility criteria, they may receive additional cycles of HER2-CAR T cells at principal investigator's discretion.

Biological: Chimeric Antigen Receptor T-Cell Therapy

Treatment (HER2-CAR T cells) - TN/MEM Naive and Memory T cell

EXPERIMENTAL

Patients receive HER2-CAR T cells (TN/MEM Naive and Memory T cell) via intraventricular administration over 5 minutes once weekly for 3 doses in the absence of disease progression or unacceptable toxicity. If patients continue to meet all eligibility criteria, they may receive additional cycles of HER2-CAR T cells at principal investigator's discretion.

Biological: Chimeric Antigen Receptor T-Cell Therapy

Interventions

Chimeric Antigen Receptor T-Cell Therapy BIOLOGICAL

Given HER2-CAR T cells via intraventricular administration

Also known as: CAR T Infusion, CAR T Therapy, CAR T-cell therapy, Chimeric Antigen Receptor T-cell Infusion

Treatment (HER2-CAR T cells) - TCM Central Memory T cell; Treatment (HER2-CAR T cells) - TN/MEM Naive and Memory T cell

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• SCREENING: Participant has treated brain and/or leptomeningeal metastases that has not recurred OR
• Such participants are eligible to enroll in the study and undergo leukapheresis, but they cannot start treatment with HER2-CAR T cells until there is evidence of tumor progression/recurrence
• SCREENING: Participant has recurrent brain metastases after radiation therapy OR
• SCREENING: Participant has recurrent leptomeningeal metastases after intrathecal chemotherapy OR
• SCREENING: Participant has untreated brain or leptomeningeal metastases and refuses to undergo radiation and/or intrathecal chemotherapy
• Note: Participants with leptomeningeal metastasis (diagnosed by positive CSF cytology or characteristic findings on brain or spine magnetic resonance imaging \[MRI\]) may have concomitant brain metastases, but having both is not required
• SCREENING: Participant must have a Karnofsky performance status (KPS) \>= 70
• SCREENING: Participant must have a life expectancy of \>= 8 weeks
• SCREENING: The effects of HER2-CAR T cells on a developing fetus are unknown. For this reason, women of child-bearing potential must have negative serum pregnancy test and agree to use a reliable form of birth control prior to study entry and for at least two months following duration of study participation. Male research participants must agree to use a reliable form of birth control and not donate sperm during the study and for at least six months afterwards
• SCREENING: Participant has a histologically confirmed cancer which is HER2+, defined as 3+ by immunohistochemistry (IHC) or gene amplification by fluorescence in situ hybridization (FISH)
• SCREENING: Participant must have the ability to understand and the willingness to sign a written informed consent
• ELIGIBILITY TO PROCEED WITH LEUKAPHERESIS: At least 2 weeks must have elapsed since the participant received his/her last dose of prior targeted agents, chemotherapy or radiation; at the PI's discretion, exception can be made for investigational agents that are delivered locally into the CSF
• ELIGIBILITY TO PROCEED WITH LEUKAPHERESIS: Research participant must not require more than 6 mg/day of dexamethasone (or the equivalent dose of another corticosteroid) on the day of leukapheresis
• ELIGIBILITY TO PROCEED WITH LEUKAPHERESIS: Participant must be willing to undergo placement of a catheter for central venous access if s/he does not have adequate peripheral venous access for collection of T cells
• ELIGIBILITY TO PROCEED WITH RICKHAM RESERVOIR PLACEMENT: Creatinine \< 1.6 mg/dL

You may not qualify if:

• Research participants with new symptoms of CHF, cardiomyopathy, myocarditis, MI, or exposure to cardiotoxic medications must have a cardiac consultation, creatinine phosphokinase (CPK), and troponin testing at pre study and as clinically indicated

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator
• California Institute for Regenerative Medicine (CIRM): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Neoplasms; Brain Neoplasms; Meningeal Carcinomatosis; Breast Neoplasms

Interventions

Immunotherapy, Adoptive

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Jana L Portnow

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2018
• First Posted: October 4, 2018
• Study Start: August 31, 2018
• Primary Completion (Estimated): January 24, 2027
• Study Completion (Estimated): January 24, 2027
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

US (1)