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
18 Years
N/A
Both
Breast Cancer
Trial Information
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
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Cardiac safety
Outcome Time Frame:
Throughout treatment and up to 30 days post-treatment
Safety Issue:
Yes
Principal Investigator
Mary Cianfrocca, DO
Investigator Role:
Principal Investigator
Investigator Affiliation:
Robert H. Lurie Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
NU 05B5
NCT ID:
NCT00316875
Start Date:
May 2006
Completion Date:
December 2014
Related Keywords:
- Breast Cancer
- stage IV breast cancer
- recurrent breast cancer
- male breast cancer
- Breast Neoplasms
Name | Location |
|---|---|
| Robert H. Lurie Comprehensive Cancer Center at Northwestern University | Chicago, Illinois 60611 |
