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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


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Breast Cancer

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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 UniversityChicago, Illinois  60611