Pilot Neoadjuvant Trial in Breast Cancer With Combination of ABI-007 (Abraxane) and GW572016 (Lapatinib)
18 Years
N/A
Both
Breast Cancer
Trial Information
Pilot Neoadjuvant Trial in Breast Cancer With Combination of ABI-007 (Abraxane) and GW572016 (Lapatinib)
OBJECTIVES:
Primary
- Determine the clinical response rate, as measured by clinical exam and imaging studies,
in patients with stage I-III breast cancer treated with neoadjuvant Abraxane in
combination with lapatinib.
Secondary
- Determine the pathologic complete response rate in patients treated with this regimen.
- Correlate proliferation (Ki67), apoptosis (cleaved caspase-3), and angiogenesis (vW,
CD34) markers, measured before and after treatment, with tumor response in these
patients.
- Conduct other correlative studies, including epidermal growth factor receptor (EGFR),
HER2/neu, matrix metalloproteinases (MMPs), and transforming growth factor (TGF-β),
before and after treatment with this regimen to assess tumor response in these
patients.
- Determine the toxicity of this regimen in these patients.
OUTLINE: This is a pilot study. Patients are assigned to 1 of 2 treatment groups.
- Group 1: The first 10 patients receive Abraxane IV over 30 minutes on day 1 and oral
lapatinib once daily on days 1-21. Treatment repeats every 21 days for 4 courses in the
absence of disease progression or unacceptable toxicity.
- Group 2: The next 20 patients receive Abraxane and lapatinib (at a higher dose) as in
group 1. Treatment repeats every 21 days for 4 courses in the absence of disease
progression or unacceptable toxicity.
Patients undergo blood collection and tumor biopsies periodically for correlative biomarker
studies.
PROJECTED ACCRUAL: A total of 30 patients will be accrued to this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed breast cancer
- Clinical stage I-III disease
- Measurable disease defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
conventional techniques OR ≥ 10 mm with spiral CT scan
- HER2/neu 3+ by immunohistochemistry or positive by fluorescent in situ hybridization
- No known brain metastases
- Hormone receptor status unspecified
PATIENT CHARACTERISTICS:
- Menopausal status not specified
- Male or female
- Life expectancy > 12 weeks
- ECOG performance status (PS) 0-1 OR Karnofsky PS 80-100%
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500 mm^3
- Platelet count ≥ 100,000/mm^3
- Total bilirubin normal
- AST and ALT ≤ 2.5 times upper limit of normal
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- LVEF ≥ 50% as measured by echocardiogram or MUGA scan
- No other malignancy within the past year
- 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 ongoing or active infection
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- No psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled illness
- No gastrointestinal (GI) tract disease that would preclude ability to take oral
medication
- No malabsorption syndrome
- No requirement for IV alimentation
- No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy, immunotherapy, radiotherapy, or hormonal therapy for breast
cancer
- No prior treatment with epidermal growth factor receptor targeting therapies
- No prior surgical procedures affecting absorption
- No prior surgery for breast cancer
- At least 14 days since prior and no concurrent CYP3A4 inducers, including any of the
following:
- Dexamethasone or dexamethasone equivalent dose ≥ 1.5 mg/day, including any of
the following:
- Cortisone (≥ 50 mg/day)
- Hydrocortisone (≥ 40 mg/day)
- Prednisone (≥ 10 mg/day)
- Methylprednisolone (≥ 8 mg/day)
- Phenytoin
- Carbamazepine
- Phenobarbital
- Efavirenz
- Nevirapine
- Rifampin
- Rifabutin
- Rifapentine
- Hypericum perforatum (St. John's wort)
- Modafinil
- At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the
following:
- Clarithromycin
- Erythromycin
- Troleandomycin
- Delavirdine
- Ritonavir
- Indinavir
- Saquinavir
- Nelfinavir
- Amprenavir
- Lopinavir
- Itraconazole
- Ketoconazole
- Voriconazole
- Fluconazole (doses up to 150 mg/day are permitted)
- Nefazodone
- Fluvoxamine
- Verapamil
- Diltiazem
- Cimetidine
- Aprepitant
- Grapefruit or its juice
- At least 6 months since prior and no concurrent amiodarone
- At least 2 days since prior and no concurrent gastric pH modifiers*, including any of
the following:
- Cimetidine
- Ranitidine
- Nizatidine
- Famotidine
- Omeprazole
- Esomeprazole
- Rabeprazole
- Pantoprazole
- Lansoprazole
- NOTE: *Antacids are allowed within 1 hour before and after administration of study
drug
- No other concurrent investigational agents
- No other concurrent anticancer therapy, including chemotherapy, radiotherapy,
immunotherapy, or antitumor hormonal therapy
- No concurrent herbal (alternative) medicines
- No concurrent combination antiretroviral therapy for HIV-positive patients
- Concurrent bisphosphonates allowed
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Clinical response rate as measured by clinical exam and imaging studies
Outcome Description:
Clinical response rate will be assessed by a clinical exam done at baseline, then before each study treatment cycle begins and a mammogram/ultrasound done at baseline, then after 4 cycles of study treatment (1 cyle = 21 days)
Outcome Time Frame:
At Baseline, then before each treatment cycle begins and after 4 cycles of study treatment (1 cycle = 21 days)
Safety Issue:
No
Principal Investigator
Virginia G. Kaklamani, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Northwestern University
Authority:
United States: Food and Drug Administration
Study ID:
NU 05B2
NCT ID:
NCT00331630
Start Date:
May 2006
Completion Date:
August 2014
Related Keywords:
- Breast Cancer
- stage I breast cancer
- stage II breast cancer
- stage IIIA breast cancer
- stage IIIB breast cancer
- stage IIIC breast cancer
- Breast Neoplasms
Name | Location |
|---|---|
| Joe Arrington Cancer Research and Treatment Center | Lubbock, Texas 79410-1894 |
| Midwest Center for Hematology/Oncology | Joliet, Illinois 60432 |
| Hematology-Oncology Associates of Illinois | Chicago, Illinois 60611-2998 |
| Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields | Olympia Fields, Illinois 60461 |
| Northwestern University, Northwestern Medical Faculty Foundation | Chicago, Illinois 60611-3013 |
