Liposomal Doxorubicin Before Mastectomy in Treating Women With Invasive Breast Cancer - Full Text View

Sponsor:	Sidney Kimmel Comprehensive Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00290732

Purpose

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.

Condition	Intervention	Phase
Breast Cancer	Drug: pegylated liposomal doxorubicin hydrochloride Procedure: conventional surgery Procedure: neoadjuvant therapy	Phase I

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I Study Assessing the Feasibility and Safety of Intraductal Administration of Pegylated Liposomal Doxorubicin (Doxil) in Women With Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Mastectomy

Drug Information available for: Doxorubicin Doxorubicin hydrochloride

U.S. FDA Resources

Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:

Feasibility and safety after definitive surgery [ Time Frame: After definitive surgery ] [ Designated as safety issue: Yes ]
Maximum tolerated dose (MTD) after definitive surgery [ Time Frame: After definitive surgery ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Pharmacokinetics in blood and tissue after definitive surgery [ Time Frame: Baseline, 4 hrs, day2/24 hrs, day 8, day of surgery ] [ Designated as safety issue: No ]

Estimated Enrollment:	21
Study Start Date:	November 2005
Estimated Study Completion Date:	January 2013
Primary Completion Date:	May 2011 (Final data collection date for primary outcome measure)

Intervention Details:

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

Other Name: Doxorubicin HCl Liposome Injection, Dox-SL, Doxil TM

mastectomy or prophylactiv mastectomy

Other Name: mastectomy, prophylactic mastectomy

chemotherapy given prior to a patient's definitive breast surgery (e.g. mastectomy)

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.

PROJECTED ACCRUAL: A total of 21 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00290732

Locations

United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202-5289
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Vered Stearns, MD

Sidney Kimmel Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided by Sidney Kimmel Comprehensive Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Stearns V, Mori T, Jacobs LK, Khouri NF, Gabrielson E, Yoshida T, Kominsky SL, Huso DL, Jeter S, Powers P, Tarpinian K, Brown RJ, Lange JR, Rudek MA, Zhang Z, Tsangaris TN, Sukumar S. Preclinical and clinical evaluation of intraductally administered agents in early breast cancer. Sci Transl Med. 2011 Oct 26;3(106):106ra108.

Responsible Party:	Vered Stearns, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier:	NCT00290732 History of Changes
Other Study ID Numbers:	J0503 CDR0000459502, P30CA006973, JHOC-J0503, JHOC-05030803
Study First Received:	February 9, 2006
Last Updated:	July 19, 2011
Health Authority:	United States: Institutional Review Board; United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:

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

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

Doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012