Liposomal Doxorubicin Before Mastectomy in Treating Women With Invasive Breast Cancer

NCT ID: NCT00290732

Last Updated: 2013-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2011-10-31

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.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intraductal arm

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

Group Type: EXPERIMENTAL

Intraductal arm

Intervention Type: DRUG

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

Intravenous arm

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

Group Type: ACTIVE_COMPARATOR

Intravenous arm

Intervention Type: DRUG

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.

Interventions

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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Doxorubicin HCl Liposome Injection, Dox-SL, Doxil TM; Doxorubicin HCl Liposome Injection, Dox-SL, Doxil TM

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vered Stearns, MD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

References

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. doi: 10.1126/scitranslmed.3002368.

Reference Type: RESULT

PMID: 22030751 (View on PubMed)

Other Identifiers

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

JHOC-J0503

Identifier Type: OTHER

Identifier Source: secondary_id

J0503 CDR0000459502

Identifier Type: -

Identifier Source: org_study_id