Overview

This trial is active, not recruiting.

Condition breast cancer
Treatments lapatinib ditosylate, paclitaxel albumin-stabilized nanoparticle formulation
Phase phase 0
Sponsor Northwestern University
Collaborator GlaxoSmithKline
Start date May 2006
End date August 2009
Trial size 30 participants
Trial identifier NCT00331630, NU 05B2, STU00007257

Summary

RATIONALE: Drugs used in chemotherapy, such as Abraxane, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. Giving Abraxane together with lapatinib may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving Abraxane together with lapatinib works in treating patients with stage I, stage II, or stage III breast cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
30 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.
lapatinib ditosylate Tykerb
Oral lapatinib is taken once daily on days 1-21 of each treatment cycle. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
paclitaxel albumin-stabilized nanoparticle formulation Abraxane
30 patients receive Abraxane IV over 30 minutes on day 1 each of each treatment cycle. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Primary Outcomes

Measure
Clinical response rate as measured by clinical exam and imaging studies
time frame: At Baseline, then before each treatment cycle begins and after 4 cycles of study treatment (1 cycle = 21 days)

Secondary Outcomes

Measure
Pathologic complete response rate
time frame: At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
Correlation of proliferation (Ki67) with tumor response as measured at baseline and after completion of study treatment
time frame: At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
Correlation of apoptosis (cleaved caspase-3) with tumor response as measured at baseline and after completion of study treatment
time frame: At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
Correlation of angiogenesis (vW, CD34) markers with tumor response as measured at baseline and after completion of study treatment
time frame: At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
Correlation of other studies with tumor response, including epidermal growth factor receptor (EGFR), HER2/neu, matrix metalloproteinases (MMPs), and transforming growth factor (TGF-β) as measured at baseline and after completion of study treatment
time frame: At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
Side effects from the combination of Abraxane and Lapatinib
time frame: At baseline, then before the start of each study treatment cycle (1 cycle = 21 days) begins
Circulating tumor cell measurement
time frame: At baseline, then before each study treatment cycle begins (1 cycle = 21 days)

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title Pilot Neoadjuvant Trial in Breast Cancer With Combination of ABI-007 (Abraxane) and GW572016 (Lapatinib)
Principal investigator Virginia G. Kaklamani, MD
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2014.
Information provided to ClinicalTrials.gov by Northwestern University.