Abraxane and Lapatinib in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer

NCT00331630 | Completed Early Phase 1 Results DMC

• 2 other identifiers: NU 05B2STU00007257
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 5

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.

Conditions

Breast Cancer

Keywords

stage I breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer

Outcome Measures

Primary Outcomes (1)

• Clinical Response Rate (cRR)

  cRR measured by RECIST for target lesions assessed by clinical exam+ mammogram+ ultrasound (US). cRR is defined as number of patients who's best response in any of the assessments (clinical exam/mammogram/US) is CR+PR. Response will be defined as one of the following in either clinical exam, mammogram or US: Complete Response (CR)-Disappearance of all target lesions. Partial Response (PR)\>=30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum. Stable Disease-neither sufficient shrinkage to qualify for Partial disease nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD while on study. Progressive Disease \<=20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

  At Baseline, then before each treatment cycle begins and after 4 cycles of study treatment (1 cycle = 21 days)

Secondary Outcomes (6)

• Pathologic Complete Response (pCR)

  At baseline, then after 4 cycles of study treatment (1 cycle = 21 days ) and at surgery

• Proliferation (Ki67) Measured at Baseline and After Completion of Study Treatment

  At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )

• Apoptosis (Cleaved Caspase-3) Measured at Baseline and After Completion of Study Treatment

  At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )

• Angiogenesis (vW, CD34) Markers as Measured at Baseline and After Completion of Study Treatment

  At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )

• Epidermal Growth Factor Receptor (EGFR), and Matrix Metalloproteinases (MMPs), Measured at Baseline and After Completion of Study Treatment

  At baseline, then after 4 cycles of study treatment (1 cycle = 21 days )

Other Outcomes (1)

• Circulating Tumor Cell Measurement

  At baseline, then before each study treatment cycle begins (1 cycle = 21 days)

Study Arms (1)

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.

Drug: lapatinib ditosylate; Drug: paclitaxel albumin-stabilized nanoparticle formulation

Interventions

lapatinib ditosylate DRUG

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.

Also known as: Tykerb, Tyverb

Treatment arm

paclitaxel albumin-stabilized nanoparticle formulation DRUG

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.

Also known as: Abraxane, ABI-007

Treatment arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Northwestern University: lead
• GlaxoSmithKline: collaborator
• Celgene Corporation: collaborator

Study Sites (5)

Northwestern University, Northwestern Medical Faculty Foundation

Chicago, Illinois, 60611-3013, United States

Location

Hematology-Oncology Associates of Illinois

Chicago, Illinois, 60611, United States

Location

Midwest Center for Hematology/Oncology

Joliet, Illinois, 60432, United States

Location

Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields

Olympia Fields, Illinois, 60461, United States

Location

Joe Arrington Cancer Research and Treatment Center

Lubbock, Texas, 79410-1894, United States

Location

Related Publications (1)

• 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.

  PMID: 21359953 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib; Taxes; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Virginia Kaklamani
• Organization: Northwestern University

312-695-1301

Study Officials

• Virginia G. Kaklamani, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2006
• First Posted: May 31, 2006
• Study Start: May 4, 2006
• Primary Completion: November 10, 2006
• Study Completion: August 5, 2010
• Last Updated: March 6, 2020
• Results First Posted: March 6, 2020

Record last verified: 2020-01

Locations

US (5)