Clinical trial NCT00331630: Abraxane and Lapatinib in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer
Official title: Pilot Neoadjuvant Trial in Breast Cancer With Combination of ABI-007 (Abraxane) and GW572016 (Lapatinib)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Breast Cancer
Keywords: stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
name: Celgene Corporation
First posted: 2006-05-31
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Clinical Response Rate (cRR)
timeFrame: 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 (pCR)
timeFrame: At baseline, then after 4 cycles of study treatment (1 cycle = 21 days ) and at surgery
measure: Proliferation (Ki67) Measured at Baseline and After Completion of Study Treatment
timeFrame: At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
measure: Apoptosis (Cleaved Caspase-3) Measured at Baseline and After Completion of Study Treatment
timeFrame: At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
measure: Angiogenesis (vW, CD34) Markers as Measured at Baseline and After Completion of Study Treatment
timeFrame: At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
measure: Epidermal Growth Factor Receptor (EGFR), and Matrix Metalloproteinases (MMPs), Measured at Baseline and After Completion of Study Treatment
timeFrame: At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )
measure: Side Effects From the Combination of Abraxane and Lapatinib
timeFrame: At baseline, then before the start of each study treatment cycle (1 cycle = 21 days) begins
Other outcomes:
measure: Circulating Tumor Cell Measurement
timeFrame: At baseline, then before each study treatment cycle begins (1 cycle = 21 days)
Locations:
city: Chicago
country: United States
facility: Northwestern University, Northwestern Medical Faculty Foundation
state: Illinois
city: Chicago
country: United States
facility: Hematology-Oncology Associates of Illinois
state: Illinois
city: Joliet
country: United States
facility: Midwest Center for Hematology/Oncology
state: Illinois
city: Olympia Fields
country: United States
facility: Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields
state: Illinois
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research and Treatment Center
state: Texas
Study officials:
affiliation: Northwestern University
name: Virginia G. Kaklamani, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kaklamani VG, Siziopikou K, Scholtens D, Lacouture M, Gordon J, Uthe R, Meservey C, Hansen N, Khan SA, Jeruss JS, Bethke K, Cianfrocca M, Rosen S, Von Roenn J, Wayne J, Parimi V, Jovanovic B, Gradishar W. Pilot neoadjuvant trial in HER2 positive breast cancer with combination of nab-paclitaxel and lapatinib. Breast Cancer Res Treat. 2012 Apr;132(3):833-42. doi: 10.1007/s10549-011-1411-8. Epub 2011 Feb 27.