Clinical trial NCT00290732
Conditions: Breast Cancer
Keywords: stage I breast cancer stage II breast cancer stage IIIA breast cancer stage IIIC breast cancer stage IV breast cancer breast cancer in situ ductal breast carcinoma in situ
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Start date: 2005-11-01; Completion date: 2011-10-01
Enrollment: 20 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Drugs used in chemotherapy, such as liposomal doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy in different ways, such as into the breast ducts, may kill more tumor cells. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase I trial is studying the side effects and best dose of liposomal doxorubicin when given before mastectomy in treating women with invasive breast cancer.

Detailed description:
OBJECTIVES:

Primary

* Evaluate the feasibility, safety, and maximum tolerated dose of intraductal pegylated doxorubicin HCl liposome in women with invasive breast cancer awaiting mastectomy.

Secondary

* Determine the pharmacokinetics of intraductal pegylated doxorubicin HCl liposome, including serial plasma concentrations of doxorubicin and doxorubicinol and tissue concentrations in different portions of the breast at the time of surgery.

OUTLINE: This is a dose-escalation study.

Patients receive an intraductal injection of pegylated doxorubicin HCl liposome\* on day 1. Patients undergo mastectomy 2-4 weeks later.

Cohorts of 3-6 patients receive escalating doses of pegylated doxorubicin HCl liposome\* until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

NOTE: \*The first cohort of 3 patients receive intraductal dextrose only followed by surgery as a feasibility study. An additional 3 patients receiving intravenous PLD will be enrolled in a pharmacokinetic control portion of the study.

Arms: arm 1: Participants received intraductal administration of dextrose or dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD) prior to conventional surgery for breast cancer. arm 2: Participants receiving standard intravenous administration of pegylated liposomal doxorubicin prior to breast biopsy for drug concentrations.
Interventions: intervention 1: Intraductal arm intervention 2: Intravenous arm
Intervention descriptions: intervention 1: Patients will receive PLD intraductally according to the dose escalation schema (Dose Level -1=1 mg, Dose Level 1=2 mg, Dose Level 2= 5mg, Dose Level 3=10 mg). The PLD dose will be diluted in 5% dextrose in water and will be mixed for a total volume of 5 ml. The PLD will be administered via a breast duct (i.e., intraductally) using a microcatheter intervention 2: Blood samples and a breast tissue biopsy collected to look at levels of doxorubincol from patients receiving intravenous pegylated liposomal doxorubin to compare to the group receiving drug intraductally.

Protocol documents: