Chemotherapeutic Agents in Brain/Breast
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.
Drug: doxorubicin hydrochloride
Drug: gemcitabine hydrochloride
Drug: lapatinib ditosylate
Drug: vinorelbine ditartrate
|Study Design:||Observational Model: Case-Only
Time Perspective: Prospective
|Official Title:||Clinical Study to Assess Entry of Chemotherapeutic Agents Into Brain Metastases in Women With Breast Cancer|
- Concentration of drug [ Time Frame: Post-Op Per Sample Collection ] [ Designated as safety issue: No ]
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.
Biospecimen Retention: Samples With DNA
Collection of blood before and after chemotherapy is administered and before and after resection of tumor in the operating room. Analysis of small portions of the brain tumor obtained at the time of craniotomy for drug collection.
|Study Start Date:||September 2008|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||February 2013 (Final data collection date for primary outcome measure)|
- 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.
|United States, New York|
|Memorial Sloan Kettering|
|New York, New York, United States, 10065|
|United States, Ohio|
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44195|
|Principal Investigator:||David M. Peereboom, MD||Case Comprehensive Cancer Center|
|Principal Investigator:||Robert Weil, MD||The Cleveland Clinic|