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Liposomal Doxorubicin Before Mastectomy in Treating Women With Invasive Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00290732
First received: February 9, 2006
Last updated: October 7, 2013
Last verified: October 2013
  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: Intraductal arm
Drug: Intravenous arm
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel 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:


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

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: Until up to 30 days after PLD administration ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Concentrations of Doxorubicin in Blood (Plasma) at Definitive Surgery [ Time Frame: Baseline, 4 hrs, day2/24 hrs, day 8, day of surgery/biopsy ] [ Designated as safety issue: No ]
    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.

  • Concentrations of Doxorubicin in Tissue at Definitive Surgery [ Time Frame: Day of surgery/biopsy ] [ Designated as safety issue: No ]
    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.


Enrollment: 20
Study Start Date: November 2005
Study Completion Date: October 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intraductal arm
Participants received intraductal administration of dextrose or dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD) prior to conventional surgery for breast cancer.
Drug: Intraductal arm
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
Active Comparator: Intravenous arm
Participants receiving standard intravenous administration of pegylated liposomal doxorubicin prior to breast biopsy for drug concentrations.
Drug: Intravenous 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.
Other Name: Doxorubicin HCl Liposome Injection, Dox-SL, Doxil TM

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.

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Investigators
Study Chair: Vered Stearns, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00290732     History of Changes
Other Study ID Numbers: J0503 CDR0000459502, P30CA006973, JHOC-J0503
Study First Received: February 9, 2006
Results First Received: March 1, 2013
Last Updated: October 7, 2013
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
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 23, 2014