Protocol Number: 96-C-0104

Title:

A Pilot Study of Paclitaxel/Cyclophosphamide and High Dose Melphalan/Etoposide with Autologous Progenitor Cell Transplantation for the Treatment of Inflammatory Breast Cancer

Number:

96-C-0104

Summary:

This study will evaluate the effectiveness of combination chemotherapy with paclitaxel (Taxol) and cyclophosphamide (Cytoxan), followed by high-dose melphalan and etoposide for treating inflammatory breast cancer. Patients also receive infusions of their own previously collected progenitor cells (primitive cells that can make new cells to replace ones destroyed by chemotherapy).

Patients 18 years of age or older with stage IIIB inflammatory breast cancer that has not metastasized (spread beyond the breast) may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, and chest x-ray. They have computed tomography (CT) of the head, chest, abdomen and pelvis as well as a bone scan to determine the extent of disease, and a nuclear medicine scan called MUGA to examine the heart's pumping ability. They may receive a rehabilitation medicine evaluation.

Participants undergo the following tests and procedures:

- Central venous line placement: Patients have a central venous line (plastic tube) placed into a major vein in the chest before beginning treatment. The line remains in the body throughout treatment and is used to give chemotherapy and other medications and to withdraw blood samples. The line is usually placed under local anesthesia in the radiology department or the operating room.

- Chemotherapy: Patients receive two or more cycles of paclitaxel and cyclophosphamide. Paclitaxel is given intravenously (I.V., through a vein) for 72 hours using a portable pump. Cyclophosphamide is given daily for 3 days I.V. over 1 hour. The cycles may be 28 days apart. A drug called Mesna is given with this treatment to protect the bladder from irritation from cyclophosphamide. Patients who have not previously been treated with doxorubicin (Adriamycin) may receive a maximum of four cycles of doxorubicin and cyclophosphamide by vein on a single day during each cycle, with cycles 21 days apart. When all the paclitaxel/cyclophosphamide cycles are completed, patients receive melphalan and etoposide, both drugs I.V. over 1 to 8 hours for three consecutive days.

- G-CSF treatment: After each paclitaxel/cyclophosphamide cycle and after the melphalan/etoposide treatment, patients are given a drug called G-CSF. G-CSF, injected under the skin, stimulates production of infection-fighting white blood cells.

- Apheresis: This is a procedure to collect progenitor cells for later reinfusion. For this procedure, blood is collected through a catheter (plastic tube) placed in an arm vein. The blood is circulated through a cell-separating machine, where the white cells, including the progenitor cells, are extracted, and the red cells are returned to the patient through another catheter in the other arm. Apheresis is done after each of two cycles of paclitaxel/cyclophosphamide.

- Progenitor cell transplant: Progenitor cells are reinfused after melphalan/etoposide treatment.

- Glucose infusion: A salt solution with chemically modified glucose is infused I.V. over a period of from 12 to 48 hours, with subsequent donation of blood cells for blood and immune system studies. Patients have a maximum of two glucose infusions, separated by at least 3 months.

- Tumor biopsy: Some patients have a biopsy of their tumor (removal of a small piece of tumor tissue for microscopic study) before starting chemotherapy.

- Blood tests: Blood is drawn frequently to monitor safety and treatment response, and for research purposes.

- Dental consultation: Some patients may have a dental consultation before the progenitor cell transplant.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

Age greater than or equal to 18 years.

All patients must have a histologically confirmed diagnosis of Infiltrating Breast Carcinoma stage III B. IPatients with no clinical inflammatory signs but with tumor invasion of dermal lymphatic on histology are eligible. Patients with metastatic disease and Inflammatory Breast Carcinoma are not eligible. All pathologic material must be reviewed and confirmed by the Department of Pathology of the Clinical Center prior to treatment.

Patients may be untreated or may have received prior induction chemotherapy outside the NCI. They may have received chemotherapy either before (neo-adjuvant setting) or after local surgery (adjuvant setting) Karnofsky performance status of greater than 70% (ECOG 0 or 1).

Ejection fraction by MUGA or 2-D echocardiogram of greater than 45%.

Creatinine clearance of greater than 60 cc/mm.

AST and ALT less than 3X upper limit of normal.

Bilirubin less than 1.5 (except in cases of Gilbert's disease).

ANC greater than 1000/mm(3).

Platelet count greater than 90,000/mm(3).

DLCO greater than 50%.

No history of medical or psychiatric disease which would preclude safe treatment in the View of the principal investigator.

No history of abnormal bleeding tendency or predisposition to repeated infections.

Patients must be able to give informed consent.

EXCLUSION CRITERIA:

Patients with Inflammatory Breast Cancer buth with metastatic disease.

Any patient may be excluded from this study at the discretion of the principal investigator if it is deemed that allowing participation would represent an unacceptable medical or psychiatric risk.

Any patient with a need for chronic steroids or anticoagulation will be ineligible.

Any patient testing positive for HIV (AIDS) or hepatitis B or C will be ineligible.

Any female patient known or found to be pregnant will be considered ineligible. Patients of childbearing potential unwilling to practice contraception will be ineligible.

Any patient with an active second malignancy (excluding treated skin cancers or carcinoma in situ) will be ineligible.

Any patient with a history of diabetes mellitus will be excluded from receiving [6,6- (2)H(2)] or [U-(13)C(9)]-glucose infusions.

Special Instructions:

Many protocols are potentially hazardous, are intended only for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this protocol should be consulted before using this protocol. Dose and schedule modifications are required for patients who develop gastrointestinal, hematologic, neurologic, and biochemical (renal, hepatic, etc.) and/or other abnormalities after the administration of therapy. Additionally, Federal regulations for the protection of human subjects require approval of clinical trials by your local Institutional Review Board.

Keywords:

T-Cells

CD34+ Selection

T-Cell Depletion

Apheresis

Mobilization

Recruitment Keywords:

None

Conditions:

Breast Neoplasm

Neoplasm Metastasis

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

CSSC
Clinical Studies Support Center/NCI
164 Rollins Avenue
2nd FLoor
Rockville, MD 20852
Phone: (888) 624-1937
Fax: (301) 881-8239

Electronic Address: ncicssc@mail.nih.gov

Citations:

High-dose therapy with autologous bone marrow transplantation for the treatment of solid tumors

High-dose chemotherapy and autologous bone marrow support as consolidation after standard dose adjuvant therapy for high risk primary breast cancer

Lymphocyte depletion during treatment with intensive chemotherapy for cancer

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