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Chemotherapy Followed by Peripheral Stem Cell Transplantation Plus Biological Therapy in Treating Patients With Stage IIIB or Stage IV Breast Cancer or Other Solid Tumors

This study is currently recruiting participants.
Information provided by National Cancer Institute (NCI)

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Descriptive Information Fields
Brief Title  Chemotherapy Followed by Peripheral Stem Cell Transplantation Plus Biological Therapy in Treating Patients With Stage IIIB or Stage IV Breast Cancer or Other Solid Tumors
Official Title  Treatment of Stage IIIB or IV Breast Cancer or Other Solid Tumors With Activated T Cells, Low Dose IL-2, and GM-CSF After Peripheral Blood Stem Cell Transplant (Pilot Phase II)
Brief Summary

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 the side effects, best way to give, and best dose of chemotherapy followed by peripheral stem cell transplantation plus biological therapy and to see how well it works in treating patients with stage IIIB or stage IV breast cancer or other solid tumors.

Detailed Description

OBJECTIVES:

  • Determine whether the use of autologous peripheral blood stem cell transplantation followed by immunotherapy with activated T cells, low-dose interleukin-2, and sargramostim (GM-CSF) in women with stage IIIB or IV breast cancer or other solid tumors 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 disease (stage IIIB breast vs stage IV breast vs solid tumors). Patients with breast cancer are also stratified according to tumor classification (chemosensitive vs chemoresistant).

Patients receive filgrastim (G-CSF) subcutaneously (SC) daily for 5 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, thiotepa IV, and carboplatin IV on days -6, -5, and -4. Patients with chemoresistant disease receive ifosfamide IV, carboplatin IV, and etoposide IV on days -8 to -3. Patients undergo autologous PBSC transplantation on day 0.

Patients then receive ATC IV over 15-20 minutes three times per week starting day +4 for three weeks and then once weekly for at least 6 doses. Patients also receive low-dose IL-2 SC daily and sargramostim (GM-CSF) SC twice weekly on days 4 until last infusion of ATC.

Patients are followed at 3 and 6 months post-transplantation and then annually thereafter.

PROJECTED ACCRUAL: A total of 60 patients (10-15 with solid tumors) will be accrued.

Study Phase Phase II
Study Type  Interventional
Study Design  Treatment, Open Label
Primary Outcome Measure  Disease-free survival [ Designated as safety issue: No ]
Secondary Outcome Measure  Overall survival [ Designated as safety issue: No ]
Condition  Breast Cancer
Extragonadal Germ Cell Tumor
Gestational Trophoblastic Tumor
Kidney Cancer
Lung Cancer
Neuroblastoma
Ovarian Cancer
Sarcoma
Testicular Germ Cell Tumor
Unspecified Adult Solid Tumor, Protocol Specific
Intervention  Drug: aldesleukin
Drug: busulfan
Drug: carboplatin
Drug: cyclophosphamide
Drug: etoposide
Drug: filgrastim
Drug: ifosfamide
Drug: paclitaxel
Drug: sargramostim
Drug: therapeutic autologous lymphocytes
Procedure: bone marrow ablation with stem cell support
Procedure: peripheral blood stem cell transplantation
MEDLINE PMIDs
Links Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site
Recruitment Information Fields
Recruitment Status  Recruiting
Enrollment  60
Start Date  January 2000
Completion Date
Eligibility Criteria 

DISEASE CHARACTERISTICS:

  • Women with histologically confirmed stage IIIB or IV carcinoma of the breast

    • Bilateral disease allowed
    • Concurrent intraductal or lobular carcinoma in situ allowed
    • Measurable or evaluable recurrent metastatic disease

      • Nonmeasurable disease allowed if tumor or metastatic disease has been previously removed or successfully treated OR
  • Patients with diagnosis of solid tumor including but not limited to:

    • Ovarian carcinoma
    • Ewing sarcoma
    • Small cell lung cancer
    • Germ cell tumor
  • Relapsed solid tumor after prior PBSC transplantation allowed
  • 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
  • No significant CNS disease
  • Hormone receptor status:

    • Estrogen or progesterone receptor positive or negative

PATIENT CHARACTERISTICS:

  • Female (breast cancer)
  • Male or Female (solid tumor)
  • Menopausal status not specified
  • Karnofsky performance status 70-100%
  • 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
  • PFT-FEV_1 at least 60% predicted
  • DLCO2 at least 60% predicted
  • FVC at least 60% 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 bone marrow transplantation 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
  • No more than 1 prior chemotherapy regimen except as part of treatment on protocol WSU-2006-130
  • No prior solid organ allograft
  • At least 7 days since prior corticosteroids except therapeutic doses for respiratory ailments or adrenal insufficiency
  • Concurrent steroids for adrenal failure, septic shock, or pulmonary toxicity allowed
  • Concurrent hormones for non-disease related conditions (e.g., insulin for diabetes) allowed
Gender Both
Ages 18 Years and older
Accepts Healthy Volunteers No
Contacts ††
Location Countries  United States
Administrative Information Fields
NCT ID  NCT00020722
Organization ID CDR0000068707
Secondary IDs †† WSU-2007-033, RWMC-0634246
Study Sponsor  Barbara Ann Karmanos Cancer Institute
Collaborators ††
Investigators 
Study Chair:     Lawrence G. Lum, MD, DSc     Barbara Ann Karmanos Cancer Institute    
Information Provided By National Cancer Institute (NCI)
Verification Date August 2008
First Received Date  July 11, 2001
Last Updated Date August 26, 2008

 †    Required WHO trial registration data element.
††   WHO trial registration data element that is required only if it exists.




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