Liposomal Doxorubicin Before Mastectomy in Treating Women With Invasive Breast Cancer

Johns Hopkins Medicine

Status and phase: Completed; Phase 1

Conditions: Breast Cancer

Treatments: Drug: Intraductal arm; Drug: Intravenous arm

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00290732

P30CA006973 (U.S. NIH Grant/Contract)

JHOC-J0503 (Other Identifier)

J0503 CDR0000459502

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed infiltrating carcinoma of the breast meeting any of the following criteria:

  • T1-3, any N disease
  • Proven ductal carcinoma in situ

• Unresected disease

  • Planned mastectomy as definitive surgical procedure

    • Known or suspected metastatic disease allowed provided mastectomy is planned

• Nonpalpable tumor allowed (e.g., initial T2-3 tumor that responded to preoperative therapy)

• No inflammatory breast cancer or other T4 features

• Successful baseline ductogram

  • Baseline nipple aspiration procedure must identify a duct productive of nipple aspirate fluid
  • No severe nipple retraction

• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Female patients
• Menopausal status not specified
• ECOG performance status 0-2
• Absolute neutrophil count ≥1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL
• Creatinine ≤ 2 times upper limit of normal (ULN)
• Bilirubin ≤ 2 times ULN
• AST and ALT ≤ 2.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No significant history of severe allergy to iodinated contrast material or debilitating anxiety that may not allow for a ductogram

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Prior preoperative chemotherapy, trastuzumab (Herceptin®), or hormonal therapy allowed provided it was completed 7-14 days prior to study treatment
• No prior radiation therapy, excisional biopsy, breast reduction, areolar surgery, or breast implant (present or past history of implant that was removed)
• No other prior procedure that may have altered the breast ductal system in the ipsilateral breast
• No other concurrent chemotherapy, radiotherapy, endocrine therapy, or biologic agents for breast cancer
• No other concurrent investigational drugs
• Concurrent bisphosphonates allowed

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

Intraductal arm

Experimental group

Description:

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

Treatment:

Drug: Intraductal arm

Intravenous arm

Active Comparator group

Description:

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

Treatment:

Drug: Intravenous arm