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

NCT ID: NCT00316875

Last Updated: 2013-11-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2011-08-31

Brief Summary

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.

Detailed Description

OBJECTIVES:

Primary

• 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.

Secondary

• 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.

Conditions

Breast Cancer

Keywords

stage IV breast cancer; recurrent breast cancer; male breast cancer

Study Design

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

Study Groups

Lapatinib Ditosylate and Doxil

Group Type: EXPERIMENTAL

lapatinib ditosylate

Intervention Type: DRUG

1500 mg orally daily for as long as patients remain on trial (up to 8 cycles).

Doxil

Intervention Type: DRUG

Administered intravenously (IV) every 4 weeks in a dose-escalating fashion according to a set schedule

Interventions

lapatinib ditosylate

1500 mg orally daily for as long as patients remain on trial (up to 8 cycles).

Intervention Type: DRUG

Doxil

Administered intravenously (IV) every 4 weeks in a dose-escalating fashion according to a set schedule

Intervention Type: DRUG

Other Intervention Names

Doxorubicin HCL Liposome Injection; Dox-SL

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

• 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 CONCURRENT THERAPY:

• 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

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

William Gradishar

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

William J Gradishar, M.D.

Role: PRINCIPAL_INVESTIGATOR

Robert H. Lurie Cancer Center

Locations

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

Countries

United States

Other Identifiers

P30CA060553

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NU-05B5

Identifier Type: -

Identifier Source: secondary_id

NU-1838-001

Identifier Type: -

Identifier Source: secondary_id

NCI-2011-00325

Identifier Type: OTHER

Identifier Source: secondary_id

NU 05B5

Identifier Type: -

Identifier Source: org_study_id