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

NCT00924287 | Terminated Phase 1 Results DMC

• 2 other identifiers: 09004109-C-0041
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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 (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. Objectives:
• 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. Eligibility:
• 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. Design:
• 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.

Conditions

Metastatic Cancer

Keywords

Metastatic Cancer; Tumor Regression; Immunotherapy; Safety; Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants With an Objective Clinical Tumor Regression Response

  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.

  12 days

• Number of Participants With Adverse Events

  Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.

  12 days

Secondary Outcomes (1)

• Number of Participants With In Vivo Survival of Transfused Cells

  12 days

Study Arms (1)

Metastatic Cancer

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Mesna

Interventions

in vitro tumor reactive, chimeric T cell receptor (CAR ) gene-transduced PBL plus IV aldesleukin DRUG

720,000 IU/kg every 8 hours for a maximum of 15 doses

Also known as: Proleukin, IL-2, Interleukin-2

Metastatic Cancer

Cyclophosphamide DRUG

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

Also known as: Cytoxan, Neosar, Endoxan, Procytox, Revimmune

Metastatic Cancer

Fludarabine DRUG

25 mg/m\^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days.

Also known as: Fludara

Metastatic Cancer

Mesna DRUG

3 mg/kg/hour intravenously diluted in a suitable diluent over 23 hours after each cyclophosphamide dose.

Also known as: Mesnex, Uromitexan

Metastatic Cancer

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Kawakami Y, Eliyahu S, Sakaguchi K, Robbins PF, Rivoltini L, Yannelli JR, Appella E, Rosenberg SA. Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes. J Exp Med. 1994 Jul 1;180(1):347-52. doi: 10.1084/jem.180.1.347.

  PMID: 7516411 BACKGROUND

• Dudley ME, Wunderlich J, Nishimura MI, Yu D, Yang JC, Topalian SL, Schwartzentruber DJ, Hwu P, Marincola FM, Sherry R, Leitman SF, Rosenberg SA. Adoptive transfer of cloned melanoma-reactive T lymphocytes for the treatment of patients with metastatic melanoma. J Immunother. 2001 Jul-Aug;24(4):363-73. doi: 10.1097/00002371-200107000-00012.

  PMID: 11565838 BACKGROUND

• Dudley ME, Wunderlich JR, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry RM, Marincola FM, Leitman SF, Seipp CA, Rogers-Freezer L, Morton KE, Nahvi A, Mavroukakis SA, White DE, Rosenberg SA. A phase I study of nonmyeloablative chemotherapy and adoptive transfer of autologous tumor antigen-specific T lymphocytes in patients with metastatic melanoma. J Immunother. 2002 May-Jun;25(3):243-51. doi: 10.1097/01.CJI.0000016820.36510.89.

  PMID: 12000866 BACKGROUND

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms

Interventions

Receptors, Chimeric Antigen; Automobiles; aldesleukin; Interleukin-2; Cyclophosphamide; fludarabine; fludarabine phosphate; Mesna

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Receptors, Artificial; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Antigen, T-Cell; Receptors, Antigen; Receptors, Immunologic; Receptors, Cytoplasmic and Nuclear; Motor Vehicles; Transportation; Technology, Industry, and Agriculture; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Lymphokines; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids

Limitations and Caveats

This study was terminated after the first patient on study died as a result of the treatment.

Results Point of Contact

• Title: Steven A. Rosenberg
• Organization: National Cancer Institute, National Institutes of Health

sar@mail.nih.gov

301-496-4164

Study Officials

• Steven A Rosenberg, M.D.

  National Cancer Institute, National Institutes of Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: June 17, 2009
• First Posted: June 18, 2009
• Study Start: November 1, 2008
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: October 28, 2015
• Results First Posted: February 14, 2012

Record last verified: 2015-10

Locations

US (1)