Cyclophosphamide or Denileukin Diftitox Followed by Laboratory-Treated T Cells in Treating Patients With HER2/Neu-Overexpressing Metastatic Breast Cancer, Ovarian Cancer, or Non-Small Cell Lung Cancer Previously Treated With a HER2/Neu Vaccine - Full Text View

Sponsors and Collaborators:	Fred Hutchinson Cancer Research Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00228358

Purpose

RATIONALE: Laboratory-treated T cells may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Biological therapies, such as denileukin diftitox, may stimulate the immune system in different ways and stop cancer cells from growing. Giving laboratory-treated T cells together with cyclophosphamide or denileukin diftitox may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of laboratory-treated T cells when given together with cyclophosphamide or denileukin diftitox in treating patients with HER2/neu-overexpressing metastatic breast cancer, ovarian cancer, or non-small cell lung cancer previously treated with a HER-2/neu vaccine.

Condition	Intervention	Phase
Breast Cancer Lung Cancer Ovarian Cancer	Biological: denileukin diftitox Biological: ex vivo-expanded HER2-specific T cells Biological: therapeutic autologous lymphocytes Drug: cyclophosphamide	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized
Official Title:	A Phase I Study of Infusion of HER-2/Neu Specific T Cells in Patients With Advanced Stage HER-2/Neu Expressing Cancers Who Have Received a HER-2/Neu Vaccine

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Lung Cancer Ovarian Cancer

Drug Information available for: Cyclophosphamide Denileukin diftitox

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Feasibility of expanding HER2-specific T cells ex vivo [ Designated as safety issue: No ]
Safety [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Extent to which ex vivo-expanded HER2-specific T-cell immunity can be boosted [ Designated as safety issue: No ]
Antitumor effects of ex vivo-expanded HER2-specific T cells as assessed by RECIST criteria [ Designated as safety issue: No ]
Persistence of T-cell immune augmentation [ Designated as safety issue: No ]
Progression [ Designated as safety issue: No ]

Estimated Enrollment:	10
Study Start Date:	June 2003
Estimated Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group I: Experimental Patients receive cyclophosphamide IV on day -1 and autologous ex vivo-expanded HER2-specific T cells IV over 30 minutes on days 1, 10, and 20.	Biological: ex vivo-expanded HER2-specific T cells given IV Biological: therapeutic autologous lymphocytes given IV Drug: cyclophosphamide given IV
Group II: Experimental Patients receive denileukin diftitox IV over 1 hour on day -1, ex vivo-expanded HER2-specific T cells IV over 30 minutes on days 1, 10, and 20.	Biological: denileukin diftitox given IV Biological: ex vivo-expanded HER2-specific T cells given IV Biological: therapeutic autologous lymphocytes given IV

Detailed Description:

OBJECTIVES:

Primary

Assess the feasibility of cyclophosphamide vs denileukin diftitox followed by ex vivo-expanded HER2-specific T cells in patients with HER2/neu overexpressing metastatic breast, ovarian, or non-small cell lung cancer previously treated with a HER2/neu vaccine.
Assess the toxicity of these regimens in these patients.

Secondary

Determine to what extent ex vivo-expanded HER2-specific T-cell immunity can be boosted in these patients.
Determine the potential antitumor effects of these regimens in these patients.
Evaluate how long T-cell immune augmentation persists in patients treated with these regimens.

OUTLINE: This is a nonrandomized, dose-escalation study of ex vivo-expanded HER2-specific T cells. Patients are assigned to 1 of 2 treatment groups.

Previously collected autologous peripheral blood mononuclear cells are stimulated with HER2 peptide antigens and expanded ex vivo.

Group I: Previously collected autologous peripheral blood mononuclear cells are stimulated with HER2 peptide antigens and expanded ex vivo. Patients receive cyclophosphamide IV on day -1 and autologous ex vivo-expanded HER2-specific T cells IV over 30 minutes on days 1, 10, and 20.
Group II: Previously collected autologous peripheral blood mononuclear cells are stimulated with HER2 peptide antigens and expanded ex vivo. Patients receive denileukin diftitox IV over 1 hour on day -1, ex vivo-expanded HER2-specific T cells IV over 30 minutes on days 1, 10, and 20. Cohorts of 5 patients receive escalating doses of ex vivo-expanded HER2-specific T cells until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 4 of 5 patients experience dose-limiting toxicity.

Patients undergo blood collection for immunological studies. Samples are analyzed for HER2-specific baseline immunity by flow cytometry and lower level precursor frequencies of interferon gamma by ELISPOT.

After completion of study treatment, patients are followed periodically.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of breast, ovarian, or non-small cell lung cancer
- Previously treated disease
  - Not considered curable by conventional therapies, including trastuzumab (Herceptin®)
- Metastatic disease
- Progressive HER2/neu overexpressing disease (either primary or metastatic)
Measurable or evaluable disease
- Patients with breast or non-small cell lung cancer must have measurable extraskeletal disease (defined as ≥ 1 unidimensionally measurable lesion > 20 mm by conventional techniques OR > 10 mm by spiral CT scan) that can include, but is not limited to bone
- Patients with ovarian cancer may have measurable disease or abnormal CA 125 level as the only indication of progression
Must have received HER2-specific vaccinations while enrolled on a HER2 vaccine clinical trial approved by the University of Washington Human Subjects Division
- Must have undergone leukapheresis after vaccination on a clinical trial approved by the University of Washington Human Subjects Division and have product stored for clinical use
History of brain metastases allowed provided the patient has a stable head-imaging study within the past 30 days
No symptomatic pericardial effusion
Hormone receptor status not specified

PATIENT CHARACTERISTICS:

Menopausal status not specified
ECOG or Zubrod performance status 0-1
WBC ≥ 1,000/mm^3
ANC ≥ 1,000/mm^3
Hematocrit ≥ 30%
Platelet count ≥ 75,000/mm^3
Creatinine ≤ 2.0 mg/dL
Bilirubin ≤ 2.0 mg/dL
AST ≤ 2 times upper limit of normal
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 1 month after completion of study treatment
No cardiac disease, including any of the following:
- Restrictive cardiomyopathy
- Unstable angina within the past 6 months
- New York Heart Association class III-IV heart disease
No active autoimmune disease
No known history of disorders associated with immunosuppression (e.g., HIV)
No known hypersensitivity to diphtheria toxin or IL-2 (patients in group II only)

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
At least 4 weeks since prior immunosuppressive treatments and/or systemic steroid therapy
At least 1 week since prior chemotherapy or trastuzumab
- Patients who have received trastuzumab must have adequate cardiac function by MUGA scan or ECHO
No concurrent enrollment in other treatment clinical trials

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00228358

Locations

United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Recruiting
Seattle, Washington, United States, 98109-1024
Contact: Clinical Trials Office - Fred Hutchinson Cancer Research Cente 800-804-8824
Tumor Vaccine Group at the University of Washington	Recruiting
Seattle, Washington, United States, 98109
Contact: Nicole Bates 206-543-6620

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Mary (Nora) L. Disis, MD

University of Washington

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000551901, FHCRC-6223, UWCC-UW 6223, UWCC- 03-7469-D 01, UWCC-UW03011, FHCRC-6223p
Study First Received:	September 13, 2005
Last Updated:	July 7, 2009
ClinicalTrials.gov Identifier:	NCT00228358 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent breast cancer
recurrent non-small cell lung cancer
recurrent ovarian epithelial cancer
recurrent ovarian germ cell tumor

stage IV breast cancer
stage IV non-small cell lung cancer
stage IV ovarian epithelial cancer
stage IV ovarian germ cell tumor

Study placed in the following topic categories:

Thoracic Neoplasms
Immunologic Factors
Gonadal Disorders
Urogenital Neoplasms
Ovarian Diseases
Cyclophosphamide
Genital Diseases, Female
Respiratory Tract Diseases
Lung Neoplasms
Ovarian Cancer
Analgesics
Alkylating Agents
Breast Diseases
Endocrine Gland Neoplasms
Ovarian Neoplasms

Skin Diseases
Genital Neoplasms, Female
Breast Neoplasms
Endocrine System Diseases
Ovarian Epithelial Cancer
Immunosuppressive Agents
Recurrence
Carcinoma
Analgesics, Non-Narcotic
Interleukin-2
Lung Diseases
Denileukin diftitox
Non-small Cell Lung Cancer
Peripheral Nervous System Agents
Antineoplastic Agents, Alkylating

Additional relevant MeSH terms:

Thoracic Neoplasms
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Gonadal Disorders
Physiological Effects of Drugs
Urogenital Neoplasms
Ovarian Diseases
Cyclophosphamide
Genital Diseases, Female
Neoplasms by Site
Respiratory Tract Diseases
Sensory System Agents
Lung Neoplasms
Therapeutic Uses

Analgesics
Alkylating Agents
Breast Diseases
Endocrine Gland Neoplasms
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Ovarian Neoplasms
Skin Diseases
Genital Neoplasms, Female
Breast Neoplasms
Endocrine System Diseases
Immunosuppressive Agents
Pharmacologic Actions
Carcinoma
Adnexal Diseases

ClinicalTrials.gov processed this record on September 03, 2009