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

Sponsor

Northwestern University (Other)

Overall Status

Completed

CT.gov ID

NCT00316875

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: lapatinib ditosylate Drug: Doxil	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

23 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

May 1, 2006

Actual Primary Completion Date :

Aug 1, 2011

Actual Study Completion Date :

Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Cardiac safety [Throughout treatment and up to 30 days post-treatment]
Maximum tolerated dose [After the first cycle of therapy]

Secondary Outcome Measures

Pharmacokinetic profiles [After treatment completion for 12 patients treated at the maximum tolerated dose]
Efficacy [At time of disease progression]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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