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Docetaxel Followed by Surgery in Treating Women With Stage II or Stage III Breast Cancer

21 de abril de 2012 atualizado por: Bapsi Chak, MD, Vanderbilt-Ingram Cancer Center

Pilot Study of Neoadjuvant Dose Dense Docetaxel With Correlative Molecular Studies in Stage II/III Breast Cancer

RATIONALE: Dose-dense scheduling with (peg)filgrastim support may improve the clinical and pathologic complete response rate (pCR) and safety profile of single agent neoadjuvant docetaxel therapy.

PURPOSE: To evaluate whether dose-dense scheduling with (peg)filgrastim support may improve the clinical and pathologic complete response rate (pCR) and safety profile of single agent neoadjuvant docetaxel therapy. To determine the changes in molecular markers that occurs with single agent docetaxel, tissue will be obtained at the end of the four cycles of docetaxel (either by repeat biopsy or definitive surgery).

Visão geral do estudo

Descrição detalhada

OBJECTIVES:

Primary

  • Pathologic complete response rate (pCR) of dose dense docetaxel in the neoadjuvant setting.

Secondary

  • Safety and toxic effects of this regimen in these patients.
  • Tumor response rate (as measured by ultrasound) in patients treated with this regimen.
  • Determine whether early changes in markers of cell cycle position, proliferation, or apoptosis correlate with pathologic complete response rate in these patients.
  • Determine whether the molecular profile that predicts for chemoresponsiveness also predicts for response to radiotherapy (as measured by local recurrence) in these patients.
  • Determine whether tumors that demonstrate the greatest degree of change in protein expression patterns from pre- to post-docetaxel treatment will also be those that are most sensitive to chemotherapy (as measured by pathologic response rate) in these patients.

OUTLINE: This is a nonrandomized, open-label, pilot study.

  • Tissue Collection: Patients undergo tumor core biopsy (6-8 cores) and blood collection prior to initiating neoadjuvant docetaxel.
  • Neoadjuvant docetaxel with hematopoietic support: Patients receive docetaxel IV over 1 hour on day 1. Patients also receive pegfilgrastim subcutaneously (SC) on day 1 or 2 of each course OR filgrastim (G-CSF) or sargramostim (GM-CSF) SC daily beginning between day 2-4 of each course and continuing until blood counts recover. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
  • Surgery: Within 4-6 weeks after completion of neoadjuvant docetaxel, patients undergo definitive surgery.

Patients undergo tumor biopsy and blood collection periodically for pharmacokinetic, genetic, and molecular biomarker correlative studies. Samples are examined for changes in p21 protein expression (and/or p21 phosphorylation) and the protein expression profile.

After completion of study treatment, patients are followed at least every 6 months for 3 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Tipo de estudo

Intervencional

Inscrição (Real)

34

Estágio

  • Fase 2

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

    • Tennessee
      • Nashville, Tennessee, Estados Unidos, 37232-6838
        • Vanderbilt-Ingram Cancer Center
      • Nashville, Tennessee, Estados Unidos, 37208
        • Meharry Medical College

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Fêmea

Descrição

DISEASE CHARACTERISTICS:

Inclusion:

  • Histologically or cytologically confirmed invasive carcinoma of the breast by core biopsy
  • Tumor ≥ 2 cm in greatest dimension(may be either node positive or node negative disease
  • Patients with non-metastatic breast cancer who are in the judgment of the treating medical oncologist considered to be of sufficiently high risk to warrant adjuvant chemotherapy

    • Patients with internal mammary, supraclavicular and/or axillary node involvement are eligible. Patients with inflammatory breast cancer are eligible
    • Patients with T0 disease but palpable and measurable adenopathy are eligible for this trial. All sites of disease should be noted and followed
  • Hormone receptor status:

    • Not specified

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Menopausal status not specified
  • Female ≥ 18 years old
  • Absolute neutrophil count ≥ 1,000/mm^3
  • Hemoglobin ≥ 8 g/dL
  • Platelet count ≥ 100,000/mm^3
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Bilirubin normal
  • Alkaline phosphatase (AP), AST, and ALT meeting 1 of the following criteria:

    • AP normal AND AST or ALT ≤ 5 times ULN
    • AP ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN
    • AP ≤ 5 times ULN AND AST or ALT normal
  • Women of child-bearing potential, must have a negative serum pregnancy test and must use effective contraception for the duration of the study and for at least 6 months after completion of study treatment
  • Patients with prior malignancies are eligible if they have been disease free for ≥ 5 years. Patients with curative treatment of non-melanomatous skin cancer, carcinoma in situ of the cervix, contralateral DCIS treated with mastectomy are eligible even if it is diagnosed in < 5 years.

PRIOR CONCURRENT THERAPY:

  • No prior anthracycline or taxane-based chemotherapy. Patients who received chemoprevention are eligible if the chemopreventive agent has been discontinued for at least one year prior to enrollment in the current study.
  • At least 1 year since prior tamoxifen for breast cancer prevention

Exclusion:

  • Prior radiotherapy to the ipsilateral breast

    • Patients who have had radiation to the contralateral breast are eligible
  • Evidence of distant metastatic disease (i.e., lung, liver, bone, brain)
  • Pregnant of breastfeeding
  • Patients who have congestive heart failure, angina pectoris, uncontrolled cardiac arrhythmia, or other significant heart disease, or who have had a myocardial infarction within the past year
  • Patients with > grade 1 peripheral neuropathy
  • Patients with a history of hypersensitivity reaction to products containing polysorbate 80 (Tween 80)
  • Patients receiving an investigational anticancer drug within 3 weeks of registration
  • Patients with serious medical illness that in the judgment of the treating physician, places the patient at risk.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Não randomizado
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Intervenção Terapêutica
análise laboratorial de biomarcadores
análise de expressão de proteína
biópsia
cirurgia convencional
Docetaxel 75 mg/m2 IV (1-hour infusion) on day 1 of each cycle (cycle = 2 weeks) x 4 cycles
Outros nomes:
  • Taxotere
neoadjuvant therapy

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Number Participants to Achieve Pathologic Complete Response
Prazo: 3 month
whether or not patient has pathologic complete response (pCR) to dose dense docetaxel in the neoadjuvant setting (pCR = no residual viable tumor on histologic analysis)
3 month

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Safety Profile Based on Number of Patients With Each Worst-grade Toxicity
Prazo: Through 30 days after completion of treatment
Not all participants necessarily have an adverse event, thus not everyone will be accounted for in worst-grade toxicities. Likewise, one participant can potentially have more than one event in various grades 1-5 which accounts for the difference in number of patients analyzed and total number in the worst-grade toxicity tables. Tables represent the number of patients with worst-grade toxicity at each of five grades (grade 1, least severe; to grade 5, most severe) following NCI Common Toxicity Criteria
Through 30 days after completion of treatment
Tumor Response as Measured by Ultrasound
Prazo: At screening, 8 weeks and at surgery (within 14-21 days)
Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.
At screening, 8 weeks and at surgery (within 14-21 days)

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo

1 de fevereiro de 2004

Conclusão Primária (Real)

1 de março de 2008

Conclusão do estudo (Real)

1 de março de 2011

Datas de inscrição no estudo

Enviado pela primeira vez

22 de junho de 2006

Enviado pela primeira vez que atendeu aos critérios de CQ

22 de junho de 2006

Primeira postagem (Estimativa)

23 de junho de 2006

Atualizações de registro de estudo

Última Atualização Postada (Estimativa)

27 de abril de 2012

Última atualização enviada que atendeu aos critérios de controle de qualidade

21 de abril de 2012

Última verificação

1 de abril de 2012

Mais Informações

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

Ensaios clínicos em Câncer de mama

Ensaios clínicos em análise laboratorial de biomarcadores

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