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Erlotinib in Treating Patients With Breast Cancer That Can Be Removed by Surgery

2 augustus 2012 bijgewerkt door: Carlos L. Arteaga, Vanderbilt-Ingram Cancer Center

Phase II Trial of OSI-774 (Tarceva), a Human Epidermal Growth Factor (HER) (erbB, Also Known as Epidermal Growth Factor Receptor, EGFR) Tyrosine Kinase Inhibitor, in Treatment-Naïve Operable Breast Cancer

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving erlotinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well erlotinib works in treating patients with breast cancer that can be removed by surgery.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

OBJECTIVES:

Primary

  • To determine the in situ antitumor effect of neoadjuvant erlotinib hydrochloride as measured by a reduction in Ki67 and/or an increase in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL)-positive tumor cells in patients with treatment-naive, operable breast cancer.

Secondary

  • To identify a molecular profile, based on measurements of Estrogen Receptor (ER), Epidermal Growth Factor Receptor (EGFR), and a Human Epithelial Growth Factor Receptor-2(HER2), and protein expression profiles in patients with treatment-naïve, operable breast cancer that is responsive to erlotinib hydrochloride.
  • To correlate tumor concentrations of erlotinib hydrochloride with serum levels immediately before surgery.

OUTLINE: This is a multi-center study.

Patients receive oral erlotinib hydrochloride once daily for 5-14 days. Patients then undergo surgical resection within 24 hours after the last dose of erlotinib hydrochloride.

Tumor tissue samples are collected at baseline and during surgery for correlative laboratory studies. Tissue samples are stained for ER, HER2, and EGFR levels, proliferation (Ki67), and apoptosis (TUNEL) by immunohistochemistry. Levels of erlotinib hydrochloride in tissue samples are measured by matrix-assisted laser desorption/ionization mass spectrometry. Blood samples are collected on the day of surgery. Levels of erlotinib hydrochloride in blood samples are measured by liquid chromatography/mass spectrometry.

Patients are followed within 6 weeks after surgery.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

50

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigde Staten
    • Alabama
      • Birmingham, Alabama, Verenigde Staten, 35249
        • University of Alabama, Birmingham
    • Massachusetts
      • Boston, Massachusetts, Verenigde Staten, 02115
        • Dana-Farber Cancer Institute
    • North Carolina
      • Chapel Hill, North Carolina, Verenigde Staten, 27514
        • Lineberger Comprehensive Cancer Center
    • Tennessee
      • Nashville, Tennessee, Verenigde Staten, 37232
        • Vanderbilt-Ingram Cancer Center
      • Nashville, Tennessee, Verenigde Staten, 37208
        • Meharry Medical College

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  • Clinical stage I or II (T1 or T2, N0 or N1) invasive mammary carcinoma

    • Diagnosis may be made by fine needle aspiration cytology or core biopsy

      • A repeat core biopsy is not required for patients who have a paraffin embedded diagnostic core biopsy specimen available for immunohistochemical staining

Exclusion Criteria:

  • Patients with locally advanced disease who are planning to undergo preoperative neoadjuvant therapy are not eligible*

    • Locally advanced disease includes any of the following:

      • Primary tumor ≥ 5 cm (T3)
      • Tumor of any size with direct extension to the chest wall or skin (T4a-c)
      • Inflammatory breast cancer (T4d)
      • Fixed axillary lymph node metastases (N2)
      • Metastasis to ipsilateral internal mammary node (N3) NOTE: *Patients with primary tumors ≥ 5 cm (T3) or tumors involving the chest wall or skin who are not candidates for preoperative chemotherapy or who decline preoperative chemotherapy are eligible

  • Measurable residual tumor at the primary site

    • Measurable disease is defined as any mass that can be reproducibly measured by physical examination
  • Planning to undergo surgical treatment with either segmental resection or total mastectomy
  • Patients with a prior history of contralateral breast cancer are eligible if they have no evidence of recurrence of their initial primary breast cancer
  • No locally recurrent breast cancer
  • No evidence of distant metastatic disease (i.e., lung, liver, bone, or brain metastases)
  • Hormone receptor status not specified

PATIENT CHARACTERISTICS:

  • Menopausal status not specified
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • ANC ≥ 1,000/mm^3
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 times ULN
  • Serum glutamic oxaloacetic transminase (SGOT) and serum glutamic pyruvic transminase (SGPT) ≤ 1.5 times ULN
  • Must be at least 18 years old
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No serious medical illness that, in the judgement of the treating physician, places the patient at high risk of operative mortality

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior chemotherapy for this primary breast cancer
  • At least 7 days since prior tamoxifen or raloxifene as a preventive agent

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Tarceva
Geneesmiddel: erlotinib hydrochloride
Tarceva will be given orally at a dose of 150 mg/day for 5-14 days. Patients are to undergo surgical resection of their tumor within 24 hours of the last dose of Tarceva.
Andere namen:
  • OSI-774
  • erlotonib
Genetisch: TUNEL assay
Used to assess drug-induced changes in tumor cell proliferation and cell death in pre-therapy and surgical specimens
Genetisch: protein expression analysis
Used to assess drug-induced changes in tumor cell proliferation and cell death in pre-therapy and surgical specimens
Ander: immunohistochemistry staining method
Used to assess drug-induced changes in tumor cell proliferation and cell death in pre-therapy and surgical specimens
Ander: laboratory biomarker analysis
Used to assess level of expression of genetic markers in pre-therapy and surgical specimens
Ander: liquid chromatography
Used to determine blood plasma levels of Erlotinib on the day of surgery
Andere namen:
  • (LC/MS)
Ander: mass spectrometry
Used to determine blood plasma levels of Erlotinib on the day of surgery
Andere namen:
  • (LC/MS)
Ander: matrix-assisted laser desorption ionization mass spectrometry
After treatment and following surgery, intervention will be used to determine Tarceva levels in tissue
Andere namen:
  • MALDI MS
Procedure: therapeutic conventional surgery
Surgical treatment will occur within 24-hours following completion of therapy.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Number of Participants Experiencing in Situ Anti-tumor Effect of Tarceva
Tijdsspanne: 5-14 days
In situ anti-tumor effect of Tarceva as measured by a minimum 75% reduction in Ki67 compared to pre-treatment tumor cells in patients with operable breast cancer.
5-14 days

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Molecular Profile of Participants Who Are Responsive to Tarceva
Tijdsspanne: at 5-14 days
Determined by estrogen receptor status (ER) and human epidermal growth factor receptor 2 (HER2) status, which are measured by staining of 200-500 tumor cells and noting the number stained. Positive = > 10% of cell show staining, negative = < 10% of cells show staining
at 5-14 days
Average Post-treatment Plasma Level of Erlotinib Hydrochloride
Tijdsspanne: After last dose of Tarceva, at 5-14 days, and before surgery
Post-treatment plasma level in µmol/L of erlotinib hydrochloride
After last dose of Tarceva, at 5-14 days, and before surgery

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Vanderbilt-Ingram Cancer Center

Medewerkers

National Cancer Institute (NCI)

Onderzoekers

  • Studie stoel: Carlos L. Arteaga, MD, Vanderbilt-Ingram Cancer Center

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 augustus 2002

Primaire voltooiing (Werkelijk)

1 oktober 2007

Studie voltooiing (Werkelijk)

1 oktober 2007

Studieregistratiedata

Eerst ingediend

11 maart 2008

Eerst ingediend dat voldeed aan de QC-criteria

11 maart 2008

Eerst geplaatst (Schatting)

12 maart 2008

Updates van studierecords

Laatste update geplaatst (Schatting)

5 september 2012

Laatste update ingediend die voldeed aan QC-criteria

2 augustus 2012

Laatst geverifieerd

1 juli 2012

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • VICC BRE 0222
  • P50CA098131 (Subsidie/contract van de Amerikaanse NIH)
  • VU-VICC-BRE-0222
  • VU-VICC-020448
  • R01CA080195 (Subsidie/contract van de Amerikaanse NIH)

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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