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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Lawrence Lum, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT00020722
First received: July 11, 2001
Last updated: September 6, 2013
Last verified: September 2013
  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: Ifosfamide, carboplatin, and etoposide (ICE) regimen
Drug: Cyclophosphamide, Thiotepa, Carboplatin (CTC) or STAMP V (CTC)
Procedure: Leukapheresis
Procedure: peripheral blood stem cell transplantation (PBSCT)
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:
  • Disease-free survival [ Time Frame: Length of time from day of transplant until recurrence or relapse. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Length of time from day of transplant until death. ] [ Designated as safety issue: No ]

Enrollment: 5
Study Start Date: August 2007
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: therapeutic autologous lymphocytes 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 approximately 10 × 109 ATC 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

Other Names:
  • Ifex®
  • Paraplatin ®
  • Toposar®
  • VePesid®
  • Etopophos®
  • VP-16
  • Etoposide phosphate
Drug: 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.

Other Names:
  • Cytoxan®
  • Neosar®
  • Paraplatin ®
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.
Procedure: peripheral blood stem cell transplantation (PBSCT)
Will be collected either before or after peripheral blood stem cell collection for stem cell transplant.

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00020722

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
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: Lawrence Lum, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT00020722     History of Changes
Other Study ID Numbers: CDR0000068707, P30CA22453, WSU-2007-033, RWMC-0634246
Study First Received: July 11, 2001
Last Updated: September 6, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Barbara Ann Karmanos Cancer Institute:
stage IV breast cancer
recurrent breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Thiotepa
Ifosfamide
Isophosphamide mustard
Etoposide phosphate
Etoposide
Carboplatin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014