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Lapatinib and Doxorubicin Hydrochloride Liposome in Treating Patients With Metastatic Breast Cancer

This study has been completed.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
William Gradishar, Northwestern University Identifier:
First received: April 19, 2006
Last updated: November 6, 2013
Last verified: November 2013

RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving lapatinib together with doxorubicin hydrochloride liposome may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of doxorubicin hydrochloride liposome when given together with lapatinib in treating patients with metastatic breast cancer.

Condition Intervention Phase
Breast Cancer
Drug: lapatinib ditosylate
Drug: Doxil
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label Study of the Safety, Tolerability and Pharmacokinetics of Lapatinib in Combination With Liposomal Doxorubicin in Patients With Metastatic Breast Cancer

Resource links provided by NLM:

Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Cardiac safety [ Time Frame: Throughout treatment and up to 30 days post-treatment ]
  • Maximum tolerated dose [ Time Frame: After the first cycle of therapy ]

Secondary Outcome Measures:
  • Pharmacokinetic profiles [ Time Frame: After treatment completion for 12 patients treated at the maximum tolerated dose ]
  • Efficacy [ Time Frame: At time of disease progression ]

Enrollment: 23
Study Start Date: May 2006
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lapatinib Ditosylate and Doxil Drug: lapatinib ditosylate
1500 mg orally daily for as long as patients remain on trial (up to 8 cycles).
Drug: Doxil
Administered intravenously (IV) every 4 weeks in a dose-escalating fashion according to a set schedule
Other Names:
  • Doxorubicin HCL Liposome Injection
  • Dox-SL

Detailed Description:



  • Evaluate the safety, tolerability, and feasibility of pegylated doxorubicin HCl liposome (PLD) when administered with lapatinib, particularly in terms of cardiac safety, in patients with metastatic breast cancer.
  • Determine the optimally tolerated regimen (OTR) of PLD when administered with lapatinib in these patients.


  • Determine the pharmacokinetic profiles of lapatinib and PLD when given in combination at the OTR.
  • Describe any preliminary evidence of efficacy of lapatinib and PLD in these patients.

OUTLINE: This is an open-label, dose-escalation study of pegylated doxorubicin HCl liposome (PLD).

Patients receive oral lapatinib once daily on days 1-28 and PLD IV over at least 30 minutes on day 1. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Lapatinib may be continued alone in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of PLD until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose-limiting toxicity.

After completing study treatment, patients are followed for 30 days.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed adenocarcinoma of the breast with evidence of metastatic disease

    • Epidermal growth factor receptor (EGFR) and/or erbB2 positivity not required
  • Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension as ≥ 20 mm by conventional techniques OR as ≥ 10 mm by spiral CT scan
  • No known brain metastases or leptomeningeal disease
  • Hormone receptor status not specified


  • Male or female patients
  • Menopausal status not specified
  • Life expectancy ≥ 12 weeks
  • ECOG performance status 0-1
  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Bilirubin normal
  • AST/ALT ≤ 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • LVEF ≥ 50%
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Able to swallow and retain oral medication
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib
  • No gastrointestinal (GI) tract disease resulting in inability to take oral medication
  • No malabsorption syndrome or requirement for IV alimentation
  • No uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis)


  • Prior trastuzumab (Herceptin ®) allowed
  • Prior anthracyclines allowed provided total dose of doxorubicin hydrochloride ≤ 240 mg/m² or epirubicin ≤ 600 mg/m²
  • More than 4 weeks since prior major surgery, hormonal therapy (other than replacement therapy), chemotherapy (6 weeks for nitrosoureas or mitomycin C), or radiotherapy and recovered
  • No prior surgical procedures affecting absorption
  • No prior EGFR-targeting therapies
  • At least 7 days since prior and no concurrent CYP3A4 inhibitors
  • At least 7 days since prior and no concurrent gastric pH modifiers

    • Antacids allowed within 1 hour before and after lapatinib dosing
  • At least 14 days since prior and no concurrent CYP3A4 inducers, including dexamethasone or dexamethasone equivalent dose > 1.5 mg/day
  • At least 6 months since prior and no concurrent amiodarone
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent prophylactic growth factor support
  • No concurrent herbal medications
  • No other concurrent investigational agents or anticancer therapy
  Contacts and Locations
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Please refer to this study by its identifier: NCT00316875

United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
Sponsors and Collaborators
Northwestern University
National Cancer Institute (NCI)
Principal Investigator: William J Gradishar, M.D. Robert H. Lurie Cancer Center
  More Information

Responsible Party: William Gradishar, Principal Investigator, Northwestern University Identifier: NCT00316875     History of Changes
Other Study ID Numbers: NU 05B5
P30CA060553 ( US NIH Grant/Contract Award Number )
NCI-2011-00325 ( Other Identifier: NCI CTRP# )
Study First Received: April 19, 2006
Last Updated: November 6, 2013

Keywords provided by Northwestern University:
stage IV breast cancer
recurrent breast cancer
male breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors processed this record on March 29, 2017