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Ph II Letrozole + OSI-774 (Tarceva) in Post-menopausal, w/ ER and/or PR-positive Met Breast Cancer.

3 de agosto de 2012 actualizado por: Ingrid Mayer, MD, Vanderbilt-Ingram Cancer Center

A Phase II Trial of Letrozole Plus OSI-774 (Tarceva) in Post-menopausal Women With ER and/or PR-Positive Metastatic Breast Cancer

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by blocking the use of estrogen by the tumor cells. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving letrozole together with erlotinib may kill more tumor cells.

PURPOSE: This phase II clinical trial is studying how well giving letrozole together with erlotinib works in treating postmenopausal women with estrogen receptor-positive and/or progesterone receptor-positive locally recurrent or metastatic breast cancer.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

OBJECTIVES:

Primary

  • To determine the rate of clinical benefit (complete response [CR], partial response [PR], and stable disease [SD] in patients with hormone-dependent locally recurrent or metastatic breast cancer treated with letrozole in combination with erlotinib hydrochloride.

Secondary

  • To determine the time to progression (TTP) in patients treated with this regimen.
  • To evaluate the anti-tumor activity, as determined by CR and PR rates, of this regimen in these patients.
  • To evaluate the safety of this regimen in these patients.
  • To determine if tumors that are positive for epidermal growth factor receptor (EGFR) or Ser118 ER, or that overexpress human epidermal receptor (HER2) exhibit a longer TTP from the combination compared to tumors that do not express or overexpress these molecules.

OUTLINE: This is a multicenter study. Patients are stratified according to prior hormone therapy (hormone-therapy naive/first-line therapy vs prior hormonal therapy with either tamoxifen or an aromatase inhibitor in the adjuvant or metastatic setting/second-line therapy)

Patients receive oral letrozole and oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then yearly thereafter.

Tipo de estudio

Intervencionista

Inscripción (Actual)

48

Fase

  • Fase 2

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Estados Unidos
    • Georgia
      • Macon, Georgia, Estados Unidos, 31201
        • Central Georgia Hematology/Oncology Associates, P.C.
    • Kentucky
      • Hopkinsville, Kentucky, Estados Unidos, 42240
        • Jennie Stuart Medical Center
      • Paducah, Kentucky, Estados Unidos, 42002
        • Purchase Cancer Group
    • Tennessee
      • Chattanooga, Tennessee, Estados Unidos, 37404
        • Memorial Health Care System
      • Germantown, Tennessee, Estados Unidos, 38138
        • The Jones Clinic - Germantown
      • Jackson, Tennessee, Estados Unidos, 38301
        • Jackson-Madison County Hospital
      • Knoxville, Tennessee, Estados Unidos, 37909
        • Tennessee Cancer Specialists
      • Nashville, Tennessee, Estados Unidos, 37232-6838
        • Vanderbilt-Ingram Cancer Center
      • Nashville, Tennessee, Estados Unidos, 37067
        • Vanderbilt-Ingram Cancer Center - Cool Springs

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Femenino

Descripción

  • Patients must have estrogen (ER) and/or progesterone receptor (PgR)-positive, histologically confirmed adenocarcinoma of the breast with measurable (but not operable) locally recurrent disease, or measurable and/or evaluable metastatic disease (see protocol section 10.3), including isolated bone metastases.
  • Patients with available paraffin tissue blocks from either the primary or the metastatic site must submit tissue blocks for retrospective EGFR and HER2 analysis. If tissue blocks cannot be submitted, 20 unstained slides from each paraffin block must be submitted.

  • All patients must be post-menopausal females as defined by one of the following:

    • Prior bilateral oophorectomy
    • Prior bilateral ovarian irradiation
    • No menstrual period for 12 months or longer
    • If age 55 years or less and < 12 months from last menstrual period, patient must have a serum estradiol < or equal to 30 and an FSH level > 40.
  • Patients must not have had more than 1 prior chemotherapy regimen for metastatic disease and have fully recovered from any grade 2-4 toxicities related to chemotherapy. No concurrent chemotherapy is allowed while on protocol therapy.
  • Patients may have had 1 prior hormonal therapy for metastatic disease. This includes: tamoxifen, fulvestrant, anastrozole, exemestane, aminoglutethimide, megace, and letrozole. Patients may have received tamoxifen or aromatase inhibitors in the adjuvant setting.
  • Patients must not have had prior therapy with EGF receptor inhibitors.
  • Previous but not concomitant therapy with trastuzumab (Herceptin) is allowed. Patients must not have received Herceptin within 4 weeks of initiation of protocol therapy.
  • Patients must have an ECOG performance status of 0, 1, or 2.

  • Patients must have adequate hematologic, hepatic, and renal function as defined by the following within 2 weeks of initiation of therapy:

    • Absolute neutrophils > or equal to 1,500/mm3 and platelets > or equal to 100,000/mm3.
    • Bilirubin < than or equal to 1.5 upper limit of normal.
    • SGOT and SGPT < or equal to 2.5 upper limit of normal.
    • Creatinine < or equal to 1.5 upper limit of normal.
    • INR, PTT and PT in the normal range.
    • Must be 18 years of age or older.
  • Patients must not have a history of central nervous system metastases or unevaluated CNS symptoms suggestive of possible brain metastases.
  • Patients may receive concurrent radiation therapy to painful bone metastases or areas of impending bone fracture as long as radiation therapy is initiated prior to study entry and sites of evaluable disease outside the radiation port(s) are available for follow-up. Patients who have received prior radiotherapy must have recovered from toxicity induced by this treatment.
  • Patients < 55 years of age must not have received Luteinizing hormone releasing hormone (LHRH) antagonists within 3 months prior to protocol therapy.
  • Patients must not suffer from medical or psychiatric conditions that would interfere with ability to provide informed consent, communicate side effects, or comply with protocol requirements including maintenance of a compliance/pill diary.
  • Patients must be disease-free of prior invasive cancers for > 5 years with the exception of basal or squamous cancer of the skin or cervical carcinoma in situ.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: No aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: First line/hormone-therapy naive
Droga: erlotinib hydrochloride
OSI-774 150 mg/day
Otros nombres:
  • Tarceva, OSI-774
Droga: letrozole
Letrozole 2.5 mg/day
Otros nombres:
  • Fémara
Genético: fluorescence in situ hybridization
To determine HER2 gene amplification or excess copies of the HER2 gene
Otros nombres:
  • No especificado
Otro: immunohistochemistry staining method
to measure the epidermal growth factor receptors (EGFR)
Otros nombres:
  • No especificado
Otro: laboratory biomarker analysis
To determine if specific biomarkers exhibit a longer time to tumor progression after treatment with the study drugs
Otros nombres:
  • No especificado
Experimental: Second-line/prev hormone-therapy tx
Droga: erlotinib hydrochloride
OSI-774 150 mg/day
Otros nombres:
  • Tarceva, OSI-774
Droga: letrozole
Letrozole 2.5 mg/day
Otros nombres:
  • Fémara
Genético: fluorescence in situ hybridization
To determine HER2 gene amplification or excess copies of the HER2 gene
Otros nombres:
  • No especificado
Otro: immunohistochemistry staining method
to measure the epidermal growth factor receptors (EGFR)
Otros nombres:
  • No especificado
Otro: laboratory biomarker analysis
To determine if specific biomarkers exhibit a longer time to tumor progression after treatment with the study drugs
Otros nombres:
  • No especificado

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Number of Patients With Pathological Complete Response.
Periodo de tiempo: at 24 weeks
Per RECIST criteria v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions
at 24 weeks

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Median Time to Progression of Target Lesions
Periodo de tiempo: Every 12 weeks from on-study to disease progression
Time frame from study entry till discontinuation of treatment due to disease progression. Progression of target lesions is measured by RECIST criteria v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions.
Every 12 weeks from on-study to disease progression
Number of Patients With Anti-tumor Activity: Complete Response (CR) and Partial Response (PR)
Periodo de tiempo: at 24 weeks
Per RECIST criteria v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions and partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions.
at 24 weeks
Number of Patients With Worst-grade Toxicities Per Grade
Periodo de tiempo: at 24 weeks
Number of patients with worst-grade toxicities following NCI Common Toxicity Criteria: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, disabling, 5 = death
at 24 weeks

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Vanderbilt-Ingram Cancer Center

Colaboradores

National Cancer Institute (NCI)

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de noviembre de 2003

Finalización primaria (Actual)

1 de diciembre de 2008

Finalización del estudio (Actual)

1 de diciembre de 2008

Fechas de registro del estudio

Enviado por primera vez

8 de febrero de 2008

Primero enviado que cumplió con los criterios de control de calidad

8 de febrero de 2008

Publicado por primera vez (Estimar)

11 de febrero de 2008

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

9 de agosto de 2012

Última actualización enviada que cumplió con los criterios de control de calidad

3 de agosto de 2012

Última verificación

1 de agosto de 2012

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • VICC BRE 0303
  • VU-VICC-BRE-0303
  • VU-VICC-030592
  • GENENTECH-VU-VICC-BRE-0303
  • NOVARTIS-VU-VICC-BRE-0303

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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