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Chemotherapy Followed by Peripheral Stem Cell Transplantation Plus Biological Therapy in Treating Women With Stage IV Breast Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), March 2009
First Received: July 11, 2001   Last Updated: March 31, 2009   History of Changes
Sponsored by: Barbara Ann Karmanos Cancer Institute
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00020722
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation plus biological therapy may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: This phase II trial is studying how well chemotherapy followed by peripheral stem cell transplantation plus biological therapy works in treating women with stage IV breast cancer.


Condition Intervention Phase
Breast Cancer
Biological: therapeutic autologous lymphocytes
Drug: ICE regimen
Drug: carboplatin
Drug: cyclophosphamide
Drug: etoposide
Drug: high-dose chemotherapy
Drug: ifosfamide
Drug: thiotepa
Procedure: leukapheresis
Procedure: peripheral blood stem cell transplantation
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: Treatment of Stage IV Breast Cancer With Activated T Cells After Peripheral Blood Stem Cell Transplant (Pilot Phase II)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Disease-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]

Estimated Enrollment: 32
Study Start Date: January 2000
Estimated Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine whether the use of autologous peripheral blood stem cell transplantation followed by immunotherapy with activated T cells in women with stage IV breast cancer improves progression-free survival (PFS) compared to a reported mean PFS in patients treated with second-line chemotherapy with matching inclusion criteria by published trials.
  • Determine if this regimen improves clinical response and overall survival.
  • Perform sequential immune monitoring studies, including phenotyping, cytotoxic assays, EliSpots for IFNγ, selected T-cell repertoire (Vβ analysis), HER2/new tetramer analysis, and serum tumor markers.
  • Test correlations between immune function tests and clinical endpoints.

OUTLINE: Patients are stratified according to tumor classification (chemosensitive vs chemoresistant).

Patients receive filgrastim (G-CSF) subcutaneously (SC) daily for 4 days followed by peripheral blood mononuclear cell (PBMC) collection for PBSCT and generation of activated T cells (ATC). The PBMC are treated ex vivo with monoclonal antibody OKT3 to form ATC. The ATC are expanded for 12-14 days in interleukin-2 (IL-2).

Patients then receive high-dose chemotherapy. Patients with chemosensitive disease receive cyclophosphamide IV over 1 hour, thiotepa IV over 1 hour, and carboplatin IV over 1 hour on days -4, -3, and -2. Patients with chemoresistant disease receive ifosfamide IV over 1 hour, etoposide IV twice daily, and carboplatin IV over 1 hour on days -8 to -3. Patients undergo autologous PBSC transplantation on day 0 or on both day 0 and day

1.

Patients then receive ATC IV over 15-20 minutes three times per week starting approximately on day +1 for three weeks and then once weekly for at least 6 doses.

After completion of study therapy, patients are followed periodically for up to 2 years after PBSC.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Women with histologically documented metastatic carcinoma of the breast

    • Bilateral disease allowed
    • Concurrent intraductal or lobular carcinoma in situ allowed
  • Measurable or evaluable recurrent metastatic disease (stage IV) documented by radiograph, CT scan, nuclear medicine scan, or physical exam

    • Biopsy of recurrent site(s) recommended but not required
    • Nonmeasurable disease allowed if tumor or metastatic disease has been previously removed or successfully treated
  • 0 to 3+ HER2 amplification, as determined by FISH
  • No clinical evidence of active brain metastases

    • Patients with treated brain metastases (i.e., those who have received definitive radiation, chemotherapy, and/or underwent surgery) and are stable are eligible
  • Hormone receptor status:

    • Estrogen or progesterone receptor positive or negative

PATIENT CHARACTERISTICS:

  • Menopausal status not specified
  • Karnofsky performance status 70-100% OR ECOG performance status 0-2
  • Life expectancy at least 3 months
  • Granulocyte count at least 1,500/mm^3
  • Platelet count at least 50,000/mm^3
  • Hemoglobin greater than 8 g/dL
  • Bilirubin less than 1.5 times normal
  • AST, ALT, and alkaline phosphatase < 5 times upper normal
  • Creatinine less than 1.8 mg/dL
  • Creatinine clearance at least 60 mL/min
  • BUN less than 1.5 times normal
  • No myocardial infarction (MI) within the past year
  • No history of MI (> 1 year ago) with current coronary symptoms requiring medication
  • No current history of angina/coronary symptoms requiring medication
  • No clinical evidence of congestive heart failure requiring medical management
  • No significant congestive heart failure
  • No other uncontrolled or significant cardiovascular disease
  • Ejection fraction at least 45% at rest by MUGA
  • Systolic BP < 130 mm Hg and diastolic BP < 80 mm Hg

    • BP must be controlled to meet the standard by anti-hypertensive medications for at least 7 days prior to the first infusion
  • PFT-FEV_1 at least 50% predicted
  • DLCO2 at least 50% predicted
  • FVC at least 50% predicted
  • No other malignancy within the past 3 years
  • No other serious medical or psychiatric illness that would preclude study participation
  • HIV negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Prior chemotherapy regimens allowed, including prior treatment on protocol WSU-2006-130
  • Prior vaccine therapy on protocol WSU-2006-130 allowed
  • More than 4 weeks to leukapheresis since prior hormonal therapy
  • No radiation to the axial skeleton within 4 weeks of leukapheresis
  • No concurrent hormonal therapy for breast cancer

    • Hormones administered for non-disease-related condition (e.g. insulin for diabetes) allowed
  • Concurrent steroids for adrenal failure, septic shock, or pulmonary toxicity allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00020722

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201-1379
Contact: Clinical Trials Office - Barbara Ann Karmanos Cancer Institute     313-576-9363        
Sinai-Grace Hospital Recruiting
Detroit, Michigan, United States, 48235
Contact: Lawrence Lum     313-576-8326        
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Investigators
Study Chair: Lawrence G. Lum, MD, DSc Barbara Ann Karmanos Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Barbara Ann Karmanos Cancer Institute ( Lawrence G. Lum )
Study ID Numbers: CDR0000068707, WSU-2007-033, RWMC-0634246
Study First Received: July 11, 2001
Last Updated: March 31, 2009
ClinicalTrials.gov Identifier: NCT00020722     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage IV breast cancer
recurrent breast cancer

Study placed in the following topic categories:
Skin Diseases
Immunologic Factors
Breast Neoplasms
Cyclophosphamide
Carboplatin
Etoposide phosphate
Immunosuppressive Agents
Recurrence
Thiotepa
Ifosfamide
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents
Etoposide
Breast Diseases
Isophosphamide mustard

Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Skin Diseases
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Breast Neoplasms
Cyclophosphamide
Carboplatin
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Ifosfamide
Neoplasms by Site
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents
Breast Diseases

ClinicalTrials.gov processed this record on September 11, 2009