Clinical Study to Assess Entry of Chemotherapeutic Agents Into Brain Metastases in Women With Breast Cancer
- 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
- 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
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
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
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.
Observational Model: Case-Only, Time Perspective: Prospective
Concentration of drug
Serum/plasma concentrations: measured for all agents except trastuzumab by HPLC or LC-MS/MS. Trastuzumab concentrations measured by enzyme linked immunosorbent assay. Compared to tissue levels and the extent of change in serum/plasma during the surgical process will be noted. Tissue Concentrations: determined by HPLC/LC-MS/MS or by ELISA. The objective would be to compare tumor concentration to brain adjacent to tumor, which often has an intact BBB. The degree of BBB compromise in the specimens will be assessed through analysis of serum protein levels and hemoglobin.
Post-Op Per Sample Collection
David M. Peereboom, MD
Case Comprehensive Cancer Center
United States: Institutional Review Board
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center||Cleveland, Ohio 44195|
|Memorial Sloan Kettering||New York, New York 10021|