Clinical Trials /

cMet CAR RNA T Cells Targeting Breast Cancer

NCT01837602

Description:

An open-label, clinical trial of autologous cMet redirected T cells administered intratumorally (IT) in patients with breast cancer. Fifteen evaluable patients will be enrolled in stepwise fashion. Step 1 will enroll patients with metastatic breast cancer refractory to at least 1 standard therapy, step 2 will include newly diagnosed patients with operable triple negative breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: cMet CAR RNA T Cells Targeting Breast Cancer
  • Official Title: Clinical Trial of Autologous cMet Redirected T Cells Administered Intratumorally in Patients With Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: UPCC 13111, 813858
  • NCT ID: NCT01837602

Conditions

  • Metastatic Breast Cancer
  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
cMet RNA CAR T cellscMet positive breast cancer patients

Purpose

An open-label, clinical trial of autologous cMet redirected T cells administered intratumorally (IT) in patients with breast cancer. Fifteen evaluable patients will be enrolled in stepwise fashion. Step 1 will enroll patients with metastatic breast cancer refractory to at least 1 standard therapy, step 2 will include newly diagnosed patients with operable triple negative breast cancer.

Detailed Description

      This study is designed to determine the safety and feasibility of intratumoral administration
      of autologous T cells that have had genetic material transferred into the cell to redirect
      them to target breast cancer cells rather than their usual target. Eligible subjects will
      have metastatic breast cancer refractory to at least one standard therapy or to newly
      diagnosed with operable triple negative breast cancer.
    

Trial Arms

NameTypeDescriptionInterventions
cMet positive breast cancer patientsExperimentalMetastatic breast cancer patients with an accessible tumor (cutaneous, subcutaneous, or superficial) and/or a palpable adenopathy/mass, with ≥ 30% tumor cells expressing cMet as demonstrated on immunohistochemical analysis . The intensity for cMet IHC should be greater than or equal to 1+. The targeted tumor must be accessible (i.e. is not near a great vessel or the spinal cord) and can be surgically excised or biopsied.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Step 1 subjects only: metastatic breast cancer patients with an accessible tumor
                 (cutaneous, subcutaneous, or superficial) and/or palpable adenopathy/mass. The
                 targeted tumor is accessible (i.e. is not near a great vessel or the spinal cord) and
                 can be surgically excised or biopsied.
    
              -  Step 2 subjects only: Newly diagnosed, operable, triple negative breast cancer, i.e.
                 ER/PR-negative, her2/neu-negative, with tumor size between 2 - 3 cm (T2) as measured
                 by either clinical breast exam, mammogram, ultrasound or MRI, with or without
                 ipsilateral axilla node involvement (N0 or N1).
    
              -  cMet expression in ≥ 30% tumor cells as demonstrated on immuno-histochemistry analysis
                 of archival slides. The intensity for cMet IHC should be greater than or equal to 1+.
                 Punch biopsy or percutaneous core biopsy may be offered to Cohort 1 patients. To
                 establish eligibility for patients in step 1, archival tumor tissues from any
                 previously biopsied metastatic tumor deposit may be used for IHC staining. The
                 metastatic tumor nodule to be targeted for IT injection may not necessarily be the
                 same as previously biopsied metastatic site.
    
              -  Age > 18 years old
    
              -  Baseline Eastern Cooperative Oncology Group (ECOG) Clinical Performance Status 0 or 1
    
              -  Adequate hematologic function:
    
            WBC > 3.0 Plt > 75,000 Hgb > 10 g/dl Adequate renal function defined as serum creatinine <
            1.5 times upper limit of normal
    
            - Adequate hepatic function defined as: Total bilirubin < 1.5 times upper limit of normal,
            and ALT and AST < 2.5 times upper limit of normal
    
              -  Women of child bearing potential must have a negative pregnancy test (blood or urine)
                 and agree to use appropriate contraception from study screen through the duration of
                 the trial. Men must agree to use appropriate contraception from IT injection through
                 the duration of the trial.
    
              -  Signed and dated written informed consent.
    
            Exclusion Criteria:
    
              -  Step 1 subjects only: Targeted tumor near a great vessel or spinal cord
    
              -  Step 2 subjects only: Women already undergoing neoadjuvant chemotherapy to treat their
                 primary triple negative breast cancer
    
              -  Step 1 and 2 subjects:Positive for HIV-1/HIV-2
    
              -  Active hepatitis B or hepatitis C infection
    
              -  The anticipated use of the following within 2 weeks prior to apheresis and prior to
                 planned IT T-cell injection:
    
            Immunosuppressive drugs Cytotoxic chemotherapy (See Section 5.7 for complete details)
            Systemic glucocorticoids (steroid prep due to dye allergies prior to staging scans or use
            in anti-emetic prophylaxis for patients undergoing chemotherapy is allowed) Hematopoietic
            growth factors Other experimental therapy Note: Step 1 patients receiving
            non-investigational targeted therapy (lapatinib, trastuzumab, and/or pertuzumab) are
            eligible provided these medicines are at a stable dose and the patient began taking them
            more than 30 days prior to the planned IT T-cell injection.
    
              -  Anticipated use of anti-coagulants such as coumadin, heparin, or Lovenox within 14
                 days before the planned IT T-cell injection RETIRED AS OF PROTOCOL VERSION 11
    
              -  Pregnant women or nursing mothers
    
              -  History of alcohol abuse or illicit drug use within 12 months of IT T-cell injection
    
              -  Clinically significant comorbid disease or other underlying condition, including major
                 autoimmune disorders that would contraindicate study therapy or confuse interpretation
                 of study results
    
              -  Significant psychiatric disorder and any other reason that in the Investigator's
                 opinion would jeopardize protocol compliance or compromise the patient's ability to
                 give informed consent.
    
              -  Prior MI ascertained from medical history and review of systems
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Number of Serious Adverse Event
    Time Frame:Two years
    Safety Issue:
    Description:

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Active, not recruiting
    Lead Sponsor:University of Pennsylvania

    Trial Keywords

    • refractory to at least one standard therapy
    • newly diagnosed
    • with operable triple negative breast cancer

    Last Updated

    November 7, 2017