Status:

TERMINATED

Gene Therapy Using Anti-Her-2 Cells to Treat Metastatic Cancer

Lead Sponsor:

National Cancer Institute (NCI)

Conditions:

Metastatic Cancer

Eligibility:

All Genders

18+ years

Phase:

PHASE1

PHASE2

Brief Summary

Background: * Human epidermal growth factor receptor-2 (Her-2) is a gene found in both normal cells and cancer cells. Extra copies of the gene (overexpression) can cause too many Her-2 proteins (rece...

Detailed Description

Background: * We have constructed a single retroviral vector that contains a chimeric T cell receptor (CAR) that recognizes the Her-2 tumor antigen, which can be used to mediate genetic transfer of t...

Eligibility Criteria

Inclusion

  • INCLUSION CRITERIA:
  • Metastatic cancer that expresses Her-2 at greater than or equal to 2+ and assessed by immunohistochemistry (IHC) in the clinical laboratory improvement amendment (CLIA) approved test in the Laboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH).
  • Patients must have previously received systemic standard care (or effective salvage chemotherapy regimens) for metastatic disease, if known to be effective for that disease, and have been either non-responders (progressive disease) or have recurred. Subjects with estrogen receptor-positive or progesterone receptor-positive breast cancer must have progressed on or not be a candidate for anti-estrogens or aromatase inhibitors and all breast cancer patients must have progressed on or not be a candidate for an anthracycline-containing regimen and a taxane-containing regimen.
  • Patients with breast cancer must have previously received trastuzumab. Patients will not continue to receive trastuzumab during the trial period.
  • Greater than or equal to 18 years of age.
  • Willing to sign a durable power of attorney
  • Able to understand and sign the Informed Consent Document
  • Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
  • Life expectancy of greater than three months.
  • Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after receiving the preparative regimen.
  • Serology:
  • Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
  • Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by reverse transcriptase polymerase chain reaction (RT-PCR) and be hepatitis C virus ribonucleic acid (HCV RNA) negative.
  • Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
  • Hematology:
  • Absolute neutrophil count greater than 1000/mm\^3 without the support of filgrastim.
  • White blood cell (WBC) (\> 3000/mm\^3).
  • Platelet count greater than 100,000/mm\^3.
  • Hemoglobin greater than 8.0 g/dl.
  • Chemistry:
  • Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or equal to 2.5 times the upper limit of normal.
  • Serum creatinine less than or equal to 1.6 mg/dl.
  • Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
  • Left ventricular ejection fraction (LVEF) greater than or equal to 50%.
  • More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).
  • Patients who have previously received anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) antibody therapy must have a normal colonoscopy with normal colonic biopsies.
  • EXCLUSION CRITERIA
  • Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
  • Active systemic infections; coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system; myocardial infarction; cardiac arrhythmias; obstructive or restrictive pulmonary disease.
  • Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
  • Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
  • Concurrent Systemic steroid therapy
  • History of severe immediate hypersensitivity reaction to any of the agents used in this study.
  • History of coronary revascularization or ischemic symptoms
  • Documented forced expiratory volume in 1 second (FEV1) less than or equal to 60% predicted tested in patients with:
  • A prolonged history of cigarette smoking (20 pack/year of smoking within the past 2 years).
  • Symptoms of respiratory dysfunction

Exclusion

    Key Trial Info

    Start Date :

    November 1 2008

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    December 1 2010

    Estimated Enrollment :

    1 Patients enrolled

    Trial Details

    Trial ID

    NCT00924287

    Start Date

    November 1 2008

    End Date

    December 1 2010

    Last Update

    October 28 2015

    Active Locations (1)

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    Page 1 of 1 (1 locations)

    1

    National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, United States, 20892