Clinical trial NCT00290732: Liposomal Doxorubicin Before Mastectomy in Treating Women With Invasive Breast Cancer
Official title: A Phase I Study Assessing the Feasibility and Safety of Intraductal Administration of Pegylated Liposomal Doxorubicin (Doxil) in Women With Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-02-13
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Until up to 30 days after PLD administration
Secondary outcomes:
measure: Concentrations of Doxorubicin in Blood (Plasma) at Definitive Surgery
timeFrame: Baseline, 4 hrs, day2/24 hrs, day 8, day of surgery/biopsy
measure: Concentrations of Doxorubicin in Tissue at Definitive Surgery
timeFrame: Day of surgery/biopsy
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Vered Stearns, MD
role: STUDY_CHAIR
References:
citation: 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.