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Pilot Neoadjuvant Trial in Breast Cancer With Combination of ABI-007 (Abraxane) and GW572016 (Lapatinib)

Phase 0
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

Pilot Neoadjuvant Trial in Breast Cancer With Combination of ABI-007 (Abraxane) and GW572016 (Lapatinib)



- 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.


- 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

- 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

- 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

PROJECTED ACCRUAL: A total of 30 patients will be accrued to this study.

Inclusion Criteria


- 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


- 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

- No malabsorption syndrome

- No requirement for IV alimentation

- No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)


- No prior chemotherapy, immunotherapy, radiotherapy, or hormonal therapy for breast

- 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

- 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

- 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

- 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:


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:


Principal Investigator

Virginia G. Kaklamani, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Northwestern University


United States: Food and Drug Administration

Study ID:

NU 05B2



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



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