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Brief Title: Chemotherapeutic Agents in Brain/Breast
Official Title: Clinical Study to Assess Entry of Chemotherapeutic Agents Into Brain Metastases in Women With Breast Cancer
Study ID: NCT00795678
Brief Summary: RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Studying samples of tumor tissue and blood from patients may help doctors understand how well these drugs can be carried to the brain. PURPOSE: More definitive knowledge of the penetration of chemotherapeutic and other agents into the brain is necessary for the future rational design of drug and drug regimens that target brain metastases. This clinical trial is studying how well capecitabine, cyclophosphamide, doxorubicin, gemcitabine, lapatinib, paclitaxel, trastuzumab, or vinorelbine penetrates brain tumors.
Detailed Description: OBJECTIVES: * To determine the concentration of capecitabine, cyclophosphamide, doxorubicin hydrochloride, gemcitabine hydrochloride, lapatinib ditosylate, paclitaxel, trastuzumab (Herceptin®), or vinorelbine ditartrate in brain metastases in women with breast cancer. * To analyze drug penetrability by modeling the relationship between drug concentration in the tumor and drug concentration in blood samples. OUTLINE: Patients are assigned to receive 1 of the 8 agents by the patient's treating oncologist. Patients receive a single dose of the following study drugs immediately preceding surgery: oral capecitabine; cyclophosphamide IV over 30 minutes; doxorubicin hydrochloride IV over 15 minutes; gemcitabine hydrochloride IV over 30 minutes; oral lapatinib ditosylate\*; paclitaxel IV over 3 hours; trastuzumab (Herceptin®) IV over 30-90 minutes; or vinorelbine ditartrate IV over 10-30 minutes . Patients then undergo craniotomy for resection of the brain metastases. NOTE: \*Patients receive oral lapatinib ditosylate at least 3 days prior to surgery and immediately before surgery. All patients receiving cyclophosphamide, doxorubicin hydrochloride, gemcitabine hydrochloride, paclitaxel, or vinorelbine ditartrate also receive a single dose of pegfilgrastim subcutaneously (SC) 24-48 hours after the study drug administration OR filgrastim (G-CSF) SC once daily for 10 days, beginning 24-48 hours after the study drug administration. Blood samples are collected periodically for pharmacological studies. Tissue samples obtained at surgical resection and blood samples are used to establish cell lines and analyzed for drug concentration by HPLC, LC-MS/MS or ELISA.
Minimum Age: 18 Years
Eligible Ages: ADULT, OLDER_ADULT
Sex: FEMALE
Healthy Volunteers: No
Memorial Sloan Kettering, New York, New York, United States
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center, Cleveland, Ohio, United States
Name: David M. Peereboom, MD
Affiliation: Case Comprehensive Cancer Center
Role: PRINCIPAL_INVESTIGATOR
Name: Robert Weil, MD
Affiliation: The Cleveland Clinic
Role: PRINCIPAL_INVESTIGATOR