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Lapatinib in Metastatic Breast Cancer Resistant to Hormone Therapy

1. Juli 2018 aktualisiert von: Gary Schwartz

Lapatinib in Endocrine-Resistant Metastatic Breast Cancer

Two thirds or more of breast cancers are dependent on estrogen for growth. We use a number of estrogen-blocking medicines for treatment of metastatic breast cancer. The treatment response to these agents is unpredictable, however, and approximately one-third of patients with metastatic breast cancer with receptors for estrogen or progesterone have no benefit from hormonal therapy. Nearly all patients with metastatic breast cancer will eventually become resistant to hormonal therapy despite the fact that the hormone receptors are still present.

Some cells make a different class of growth factor receptor called the Epidermal Growth Factor Receptor. There is a growing body of experimental evidence showing that breast cancer cells that make Epidermal Growth Factor Receptors are more resistant to hormonal therapy and have a poorer prognosis. Several investigators have found that the Epidermal Growth Factor Receptor can activate the estrogen receptor, even in the presence of estrogen-blocking drugs. Growth of these cells can be slowed by blockade of both Epidermal Growth Factor Receptor signaling and estrogen-receptor signaling. Lapatinib is a small molecule which can inhibit two different forms of the Epidermal Growth Factor Receptor. It has been studied in people with a number of different cancers, including breast cancer, and a safe dose and its common side effects have been defined.

Our hypothesis is that the Epidermal Growth Factor Receptor is the dominant receptor pathway used by breast cancers in our patients with hormone-resistant tumors. Drugs like lapatinib which block several forms of the Epidermal Growth Factor Receptor would best be able to reverse resistance to hormonal agents.

Studienübersicht

Status

Beendet

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

All patients must have stopped their endocrine two to four weeks or longer prior to entry on study. Upon enrollment, patients will begin lapatinib at 1500 mg once a day orally. The original endocrine therapy will resume two weeks later. The lapatinib will be continued for a maximum of 26 weeks.

A history, physical examination, blood counts, and chemistries will be done at baseline, and at regular intervals through the course of the study. A CT scan and bone scan will be done prior to treatment and at weeks 14 and 26. Assays for plasma DNA will be performed on blood sampled at baseline and at multiple time points throughout the course of treatment. Percutaneous biopsies will be taken in selected patients with accessible disease, 72 hours or less prior to the start of lapatinib, and again 13-15 days, and 27-29 days following the start of lapatinib. The day 13-15 biopsy will be done just prior to the resumption of the patient's endocrine therapy. Assays for phospho-ERK, phospho-Akt, Cyclin D1, Ki-67, and IRS-1 will be performed by conventional immunohistochemistry on the biopsied tissue.

Studientyp

Interventionell

Einschreibung (Tatsächlich)

27

Phase

  • Phase 2

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

  • Vereinigte Staaten
    • Colorado
      • Aurora, Colorado, Vereinigte Staaten, 80045
        • University of Colorado Cancer Center
    • New Hampshire
      • Lebanon, New Hampshire, Vereinigte Staaten, 03756
        • Norris Cotton Cancer Center
    • New York
      • Lake Success, New York, Vereinigte Staaten, 11042
        • North Shore University Hospital

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Weiblich

Beschreibung

Inclusion Criteria:

  • Patients with histologically or cytologically proven metastatic breast cancer.
  • Patients with either estrogen or progesterone receptor positivity on the most recently examined tumor biopsy.
  • Patients must have most recently been using an anti-estrogen (tamoxifen, toremifene, raloxifene, or fulvestrant) or an aromatase inhibitor.
  • Patients must have had either a partial response or better, or stable disease for 24 weeks or longer, followed by disease progression, on the current or most recent hormonal therapy for management of metastatic breast cancer.
  • Patients must be enrolled within six weeks of defining disease progression on hormonal therapy.
  • Patients must have stopped fulvestrant at least four weeks prior and other endocrine therapy at least two weeks prior to enrollment on study.
  • Patients must have either measurable disease or at least one evaluable bone lesion that has not been irradiated. Measurable disease is not necessary.
  • Estimated life expectancy of at least 6 months.
  • ECOG performance status 0-2.
  • Adequate hematologic, hepatic, and renal function.
  • Patients must be post-menopausal, or they must be practicing either abstinence or an adequate method of contraception, or their sexual partner must be sterile.
  • All patients must be able to swallow, retain, and absorb oral medications.
  • All patients must be able to give informed consent indicating that they are aware of the investigational nature of this study.

Exclusion Criteria:

  • Patients may not have received an investigational agent within the prior four weeks.
  • Patients may not have received trastuzumab within three weeks of study entry.
  • Patients may not have had major surgery within the prior two weeks.
  • Patients may not have Class III or IV heart failure as defined by the NYHA functional classification system.
  • Patients may not have a left ventricular ejection fraction < 40% based on MUGA or echocardiogram.
  • Patients may not have uncontrolled brain metastases or leptomeningeal disease.
  • Patients may not have rapidly progressive visceral metastases.
  • Patients may not have a serious illness or conditions including clinically significant cardiac disease, angina pectoris, serious psychiatric disorder, or an active infection.
  • Patients may not be receiving concurrent medications (listed in the protocol) which may interact with lapatinib during treatment with lapatinib.

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: N / A
  • Interventionsmodell: Einzelgruppenzuweisung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: 1
Subjects will continue on their prior endocrine therapy with the addition of lapatinib at 1500 mg once daily for 26 weeks or longer.
Arzneimittel: Lapatinib
1500 mg po daily for 26 weeks or longer
Andere Namen:
  • Tykerb

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Determine the Response Rate and Progression Free Survival of Hormone Therapy-resistant Patients With Metastatic Breast Cancer Treated With the Same Continued Hormonal Agent With the Addition of Lapatinib.
Zeitfenster: 26 weeks
A response is defined as stable disease or better at 26 weeks. Twenty two patients are evaluable for response
26 weeks
Progression-free Survival
Zeitfenster: Up to 575 days
Progression-free survival is the time between date on study and progression based on RECIST criteria.
Up to 575 days

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Zeitfenster
Determine the Toxicities of the Combination of the Hormonal Agent and Lapatinib in Patients With Metastatic Breast Cancer
Zeitfenster: 26 weeks
26 weeks
Determine Changes in Activation of Tumor Cell ERK and Akt, as Between the Hormonal Agent and Lapatinib Contributes to the Molecular Pharmacodynamic Effect Postulated Above.
Zeitfenster: 4 weeks
4 weeks
Determine Whether Changes in Plasma DNA Concentrations Are Predictive Markers of an Early Response to Lapatinib
Zeitfenster: 14 weeks
14 weeks

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Gary Schwartz

Mitarbeiter

University of Colorado, Denver
North Shore University Hospital

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn

1. Januar 2006

Primärer Abschluss (Tatsächlich)

1. Oktober 2011

Studienabschluss (Tatsächlich)

1. Oktober 2011

Studienanmeldedaten

Zuerst eingereicht

22. September 2005

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

22. September 2005

Zuerst gepostet (Schätzen)

26. September 2005

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

27. Juli 2018

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

1. Juli 2018

Zuletzt verifiziert

1. Juli 2018

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • D-0520

Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .

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