Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Carcinoma in Situ

Breast Carcinoma In Situ

Carcinoma, Intraductal, Noninfiltrating

Carcinoma, Ductal, Breast

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Participants received intraductal administration of dextrose or dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD) prior to conventional surgery for breast cancer.

Participants receiving standard intravenous administration of pegylated liposomal doxorubicin prior to breast biopsy for drug concentrations.

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

Intraductal arm

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.

Intravenous arm

Vered Stearns, MD

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.

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.

Liposomal Doxorubicin Before Mastectomy in Treating Women With Invasive Breast Cancer

A Phase I Study Assessing the Feasibility and Safety of Intraductal Administration of Pegylated Liposomal Doxorubicin (Doxil) in Women With Breast Cancer

Maximum tolerated dose (MTD) of administering pegylated liposomal doxorubicin (PLD) into one duct of women with breast cancer awaiting mastectomy. MTD reflects highest dose of drug that did not cause Dose Limiting Toxicity (DLT) in more than 30% of patients.

Due to the limited number of samples and detectable levels, the maximum concentration of doxorubicin in blood (plasma) across all the participants in each group is reported.

Due to the limited number of samples and detectable levels, the maximum concentration of doxorubicin in tissue across all the participants in each group is reported.

National Cancer Institute (NCI)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Note: Adverse events were not collected in the intravenous group/arm; only the concentration of doxorubicin in tissue applied to this group of participants.

Intraductal Arm- 0 mg PLD

Intraductal Arm- 2 mg PLD

Intraductal Arm- 5 mg PLD

Intraductal Arm- 10 mg PLD

Intravenous Arm

Intraductal Arm

Total

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

Duct cannulation was not successful in all participants; possibly due to extensive disease or prior excisional biopsy (2 subjects).

Dr. Vered Stearns

Participants received intraductal administration of dextrose prior to conventional surgery for breast cancer.

Maximum Tolerated Dose (MTD)

Doxorubicin, max

Doxorubicinol, max

Participants received intraductal administration of dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD), 2 mg, prior to conventional surgery for breast cancer.

Participants received intraductal administration of dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD), 5 mg, prior to conventional surgery for breast cancer.

Participants received intraductal administration of dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD), 10 mg, prior to conventional surgery for breast cancer.

Participants in whom blood and/or tissue samples were collected at surgery or breast biopsy.

Concentrations of Doxorubicin in Blood (Plasma) at Definitive Surgery

Concentrations of Doxorubicin in Tissue at Definitive Surgery

Participants received intraductal administration of pegylated liposomal doxorubicin hydrochloride (or PLD), 2 mg, prior to conventional surgery for breast cancer.

Participants received intraductal administration of pegylated liposomal doxorubicin hydrochloride (or PLD), 5 mg, prior to conventional surgery for breast cancer.

Participants received intraductal administration of pegylated liposomal doxorubicin hydrochloride (or PLD), 10 mg, prior to conventional surgery for breast cancer.

Spots Global Cancer Trial Database for intravenous arm