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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00924287
Recruitment Status : Terminated (This study was terminated after the first patient treated on study died as a result of the treatment.)
First Posted : June 18, 2009
Results First Posted : February 14, 2012
Last Update Posted : October 28, 2015
Information provided by (Responsible Party):
Steven Rosenberg, M.D., National Institutes of Health Clinical Center (CC)

Brief Summary:


  • 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 (receptors) to appear on the cell surface and cause tumors to grow.
  • An experimental procedure developed for treating patients with cancer uses blood cells found in their tumors or bloodstream. The cells are genetically modified using the anti-Her-2 gene and a type of virus. The modified cells (anti-Her-2 cells) are grown in the laboratory and then given back to the patient to try to decrease the size of the tumors. This is called gene therapy.


  • To determine whether advanced cancers that overexpress Her-2 can be treated effectively with lymphocytes (white blood cells) that have been genetically engineered to contain an anti-Her-2 protein.


  • Patients 18 years of age and older with metastatic cancer (cancer that has spread beyond the original site) and for whom standard treatments are not effective.
  • Patient's tumor overexpresses Her-2.


  • Workup with scans, x-rays and other tests.
  • Leukapheresis to obtain cells for preparing the anti-Her-2 cells for later infusion.
  • 1 week of chemotherapy to prepare the immune system for receiving the anti-Her-2 cells.
  • Infusion of anti-Her-2 cells, followed by interleukin-2 (IL-2) treatment. The cells are given as an infusion through a vein. IL-2 is given as a 15-minute infusion through a vein every 8 hours for a maximum of 15 doses.
  • Periodic follow-up clinic visits after hospital discharge for physical examination, review of treatment side effects, laboratory tests and scans every 1 to 6 months.

Condition or disease Intervention/treatment Phase
Metastatic Cancer Drug: in vitro tumor reactive, chimeric T cell receptor (CAR ) gene-transduced PBL plus IV aldesleukin Drug: Cyclophosphamide Drug: Fludarabine Drug: Mesna Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study of Metastatic Cancer That Expresses Her-2 Using Lymphodepleting Conditioning Followed by Infusion of Anti-Her-2 Gene Engineered Lymphocytes
Study Start Date : November 2008
Actual Primary Completion Date : December 2010
Actual Study Completion Date : December 2010

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Metastatic Cancer
Cancer that has invaded other parts of the body
Drug: in vitro tumor reactive, chimeric T cell receptor (CAR ) gene-transduced PBL plus IV aldesleukin
720,000 IU/kg every 8 hours for a maximum of 15 doses
Other Names:
  • Proleukin
  • IL-2
  • Interleukin-2
Drug: Cyclophosphamide
60 mg/kg/day x 2 days intravenously (IV) in 250 ml 5% dextrose in water (D5W) with mesna 15 mg/kg/day x 2 days over 1 hour
Other Names:
  • Cytoxan
  • Neosar
  • Endoxan
  • Procytox
  • Revimmune
Drug: Fludarabine
25 mg/m^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days.
Other Name: Fludara
Drug: Mesna
3 mg/kg/hour intravenously diluted in a suitable diluent over 23 hours after each cyclophosphamide dose.
Other Names:
  • Mesnex
  • Uromitexan

Primary Outcome Measures :
  1. Number of Participants With an Objective Clinical Tumor Regression Response [ Time Frame: 12 days ]
    Response Evaluation Criteria in Solid Tumors (RECIST) are used to determine objective clinical response. Complete Rresponse (CR) is the disappearance of all target lesions, partial response (PR) is at least a 30% decrease in the target lesions, progressive disease (PD) is at least a 20% increase in the target lesions or appearance of one or more new lesions, and stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

  2. Number of Participants With Adverse Events [ Time Frame: 12 days ]
    Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.

Secondary Outcome Measures :
  1. Number of Participants With In Vivo Survival of Transfused Cells [ Time Frame: 12 days ]
    In-vivo survival of infused cells is determined by analysis of the sequence of the variable region of the T cell receptor or flow cytometry (FACS).

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

    1. 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).
    2. 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.
    3. Patients with breast cancer must have previously received trastuzumab. Patients will not continue to receive trastuzumab during the trial period.
    4. Greater than or equal to 18 years of age.
    5. Willing to sign a durable power of attorney
    6. Able to understand and sign the Informed Consent Document
    7. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
    8. Life expectancy of greater than three months.
    9. 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.
    10. Serology:

      1. 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.)
      2. 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.
      3. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
    11. Hematology:

      1. Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim.
      2. White blood cell (WBC) (> 3000/mm^3).
      3. Platelet count greater than 100,000/mm^3.
      4. Hemoglobin greater than 8.0 g/dl.
    12. Chemistry:

      1. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or equal to 2.5 times the upper limit of normal.
      2. Serum creatinine less than or equal to 1.6 mg/dl.
      3. 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.
    13. Left ventricular ejection fraction (LVEF) greater than or equal to 50%.
    14. 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).
    15. Patients who have previously received anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) antibody therapy must have a normal colonoscopy with normal colonic biopsies.


  1. 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.
  2. 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.
  3. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
  4. 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).
  5. Concurrent Systemic steroid therapy
  6. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
  7. History of coronary revascularization or ischemic symptoms
  8. Documented forced expiratory volume in 1 second (FEV1) less than or equal to 60% predicted tested in patients with:

    1. A prolonged history of cigarette smoking (20 pack/year of smoking within the past 2 years).
    2. Symptoms of respiratory dysfunction

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00924287

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Steven A Rosenberg, M.D. National Cancer Institute, National Institutes of Health

Responsible Party: Steven Rosenberg, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC) Identifier: NCT00924287     History of Changes
Obsolete Identifiers: NCT00805987
Other Study ID Numbers: 090041
First Posted: June 18, 2009    Key Record Dates
Results First Posted: February 14, 2012
Last Update Posted: October 28, 2015
Last Verified: October 2015

Keywords provided by Steven Rosenberg, M.D., National Institutes of Health Clinical Center (CC):
Metastatic Cancer
Tumor Regression

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms, Second Primary
Neoplastic Processes
Pathologic Processes
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents