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

Breast Cancer Clinical Trial

Official title:

Treatment of Stage IV Breast Cancer With Activated T Cells After Peripheral Blood Stem Cell Transplant (Pilot Phase II)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00020722
• Other study ID #: CDR0000068707
• Secondary ID: P30CA022453WSU-2
• Status: Terminated
• Phase: Phase 2
• First received: July 11, 2001
• Last updated: February 15, 2016
• Start date: August 2007
• Est. completion date: March 2013

Study information

• Verified date: February 2016
• Source: Barbara Ann Karmanos Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 120 Years

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• therapeutic autologous lymphocytes
Immediately after pheresis, the lymphocytes will be activated with soluble monoclonal anti-CD3 antibody (OKT3) which cross-links the CD3 receptors on T cells and activates T cells. The time for ATC infusions will vary from patient to patient, but the infusion rate will be based on the rate calculated from the endotoxin level in the cell product. All patients will be observed for at least 1 hr after an infusion.

Drug:
• Ifosfamide, carboplatin, and etoposide (ICE) regimen
Ifosfamide 2,500 mg/m2 given IV daily on day -8, -7, -6, -5, -4, and -3 prior to PBSCT. Ifosfamide 2,500 mg/m2 infused IV over 1 hour (hour 0-1) on days -8 to -3 for a total dose of 15,000 mg/m2. Mesna will be administered per BMT Standard of Care Guideline at a dose of 25% of the total Ifosfamide dose 30 minutes prior to and then 3, 6, and 9 hours after ifosfamide daily on days -8, -7, -6, -5, -4, and -3 prior to PBSCT for a total dose of 2500 mg/m2. Carboplatin at a dose of 250 mg/m2 will be given daily on days -8, -7, -6, -5, -4, and -3 prior to PBSCT for a total dose of 1500 mg/m2. VP-16 (etoposide) at a dose of 200 mg/m2 will be given IV on days -8, -7, -6, -5, -4 and -3. The total dose of VP-16 given prior to PBSCT will be 2,400 mg/m2. VP-16 will be given 200 mg/m2
• Cyclophosphamide, Thiotepa, Carboplatin (CTC) or STAMP V (CTC)
Cyclophosphamide will be given at a dose of 2000 mg/m2 in NS IV over one hour daily on days -4, -3, and -2 (total = 6000 mg/m2). Thiotepa will be given at a dose of 167 mg/m2 in NS IV over one hour daily on days -4, -3, -2 (total = 500 mg/m2) as the preparative regimen followed by PBSCT on day 0. Carboplatin will be given at a dose of 267 mg/m2 in D5W IV over one hour daily on days -4, -3, and -2. Mesna will be administered per BMT Standard of Care Guidelines at a dose of 25% of the total cyclophosphamide dose 30 minutes prior to and then 3, 6, and 9 hours after cyclophosphamide daily on days -4, -3, and -2 prior to PBSCT for a total of 2000mg/m2.

Procedure:
• Leukapheresis
Peripheral blood mononuclear cells (PBMC) will be collected by leukapheresis (for generation of ATC) prior to or post G-CSF (16 ug/kg/day) priming for collecting stem cells.
• peripheral blood stem cell transplantation (PBSCT)
Will be collected either before or after peripheral blood stem cell collection for stem cell transplant.

Locations

Country	Name	City	State
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Barbara Ann Karmanos Cancer Institute	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free Survival		Length of time from day of transplant until recurrence or relapse.	No
Secondary	Overall Survival		Length of time from day of transplant until death.	No