Liposomal Doxorubicin Before Mastectomy in Treating Women With Invasive Breast Cancer

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00290732
• Other study ID #: J0503 CDR0000459502
• Secondary ID: P30CA006973JHOC-
• Status: Completed
• Phase: Phase 1
• First received: February 9, 2006
• Last updated: October 7, 2013
• Start date: November 2005
• Est. completion date: October 2011

Study information

• Verified date: October 2013
• Source: Sidney Kimmel Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: October 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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
• 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.

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 agent — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)	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.	Until up to 30 days after PLD administration	Yes
Secondary	Concentrations of Doxorubicin in Blood (Plasma) at Definitive Surgery	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.	Baseline, 4 hrs, day2/24 hrs, day 8, day of surgery/biopsy	No
Secondary	Concentrations of Doxorubicin in Tissue at Definitive Surgery	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.	Day of surgery/biopsy	No