Clinical trial NCT00795678: Chemotherapeutic Agents in Brain/Breast
Official title: Clinical Study to Assess Entry of Chemotherapeutic Agents Into Brain Metastases in Women With Breast Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Metastatic Cancer
Keywords: tumors metastatic to brain
stage IV breast cancer
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
name: National Cancer Institute (NCI)
First posted: 2008-11-21
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will be recruited from a population of breast cancer patients who are to undergo clinically indicated surgical resection of one of more symptomatic brain metastasis(es) treated at the investigational centers.

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.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed breast carcinoma with ≥ 1 suspected or known parenchymal brain metastases for which surgical resection or biopsy is clinically indicated
* Treating oncologist must agree that the patient would derive clinical benefit from receiving ≥ 1 of the following study agents:

  * Capecitabine, cyclophosphamide, doxorubicin hydrochloride, gemcitabine hydrochloride, lapatinib ditosylate, paclitaxel, trastuzumab (Herceptin®), or vinorelbine ditartrate
* Hormone receptor status not specified

PATIENT CHARACTERISTICS:

* Menopausal status not specified
* Karnofsky performance status 50-100%
* Life expectancy ≥ 3 months
* Absolute granulocyte count ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Hemoglobin ≥ 10 g/dL
* Creatinine ≤ 1.5 times upper limit of normal (ULN)
* Bilirubin (total) ≤ 1.5 times ULN
* AST ≤ 3 times ULN
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for three months after completion of study treatment
* No severe NYHA class III-IV cardiac insufficiency with uncontrolled and/or unstable cardiac or coronary artery disease
* No history of noncompliance to medical regimens or inability or unwillingness to return for all scheduled visits

PRIOR CONCURRENT THERAPY:

* No toxicity \> grade 2 from prior chemotherapy or radiotherapy remains at the time of study entry
* At least 60 days since prior bevacizumab
* At least 4 weeks since prior cranial radiotherapy
* At least 3 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas or mitomycin C)
* At least 2 weeks since prior non-cytotoxic drugs (e.g., small molecule-targeted drugs)
* No concurrent experimental therapies
* Concurrent hormone therapy and/or trastuzumab (Herceptin®) allowed

Primary outcomes:
measure: Concentration of drug
timeFrame: Post-Op Per Sample Collection
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Case Comprehensive Cancer Center
name: David M. Peereboom, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Robert Weil, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Morikawa A, Peereboom DM, Thorsheim HR, Samala R, Balyan R, Murphy CG, Lockman PR, Simmons A, Weil RJ, Tabar V, Steeg PS, Smith QR, Seidman AD. Capecitabine and lapatinib uptake in surgically resected brain metastases from metastatic breast cancer patients: a prospective study. Neuro Oncol. 2015 Feb;17(2):289-95. doi: 10.1093/neuonc/nou141. Epub 2014 Jul 11.