Clinical trial NCT00020722: Chemotherapy Followed by Peripheral Stem Cell Transplantation Plus Biological Therapy in Treating Women With Stage IV Breast Cancer
Official title: Treatment of Stage IV Breast Cancer With Activated T Cells After Peripheral Blood Stem Cell Transplant (Pilot Phase II)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage IV breast cancer
recurrent breast cancer
Lead sponsor: Barbara Ann Karmanos Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 7
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 how well chemotherapy followed by peripheral stem cell transplantation plus biological therapy works in treating women with stage IV breast cancer.

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 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

Primary outcomes:
measure: Disease-free Survival
timeFrame: Length of time from day of transplant until recurrence or relapse.
Secondary outcomes:
measure: Overall Survival
timeFrame: Length of time from day of transplant until death.
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
Study officials:
affiliation: Barbara Ann Karmanos Cancer Institute
name: Lawrence G. Lum, MD, DSc
role: STUDY_CHAIR
References: