Chemotherapy Followed by Peripheral Stem Cell Transplantation Plus Biological Therapy in Treating Women With Stage IV Breast Cancer

Barbara Ann Karmanos Cancer Institute

Status and phase

Terminated

Phase 2

Conditions

Breast Cancer

Treatments

Drug: Cyclophosphamide, Thiotepa, Carboplatin (CTC) or STAMP V (CTC)

Procedure: Leukapheresis

Biological: therapeutic autologous lymphocytes

Procedure: peripheral blood stem cell transplantation (PBSCT)

Drug: Ifosfamide, carboplatin, and etoposide (ICE) regimen

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00020722

WSU-2007-033 (Other Identifier)

CDR0000068707

RWMC-0634246 (Other Identifier)

P30CA022453 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

7 patients

Sex

Female

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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