Esta página foi traduzida automaticamente e a precisão da tradução não é garantida. Por favor, consulte o versão em inglês para um texto fonte.

Safety & Efficacy of Three Docetaxel-Based Chemotherapy Regimens Plus Bevacizumab With or Without Trastuzumab for Adjuvant Treatment of Patients With Breast Cancer

16 de agosto de 2012 atualizado por: Sanofi

A Phase IIb, Randomized, Multicenter, Noncomparative Pilot Study of the Safety & Efficacy of Three Docetaxel-Based Chemotherapy Regimens Plus Bevacizumab ± Trastuzumab for the Adjuvant Treatment of Patients With Node-Positive & High-Risk Node-Negative Breast Cancer

This is a phase IIb, randomized, parallel-group, noncomparative, multicenter, pilot study designed to evaluate the safety and efficacy of bevacizumab with or without (+/-) trastuzumab administered with three different docetaxel-based combination regimens for the adjuvant treatment of participants with node positive or high-risk node negative breast cancer.

Visão geral do estudo

Status

Concluído

Condições

Intervenção / Tratamento

Descrição detalhada

In this study, participants were stratified according to HER2 status at the time of enrollment. HER2-negative participants were randomized in a 1:1 ratio to either stratum 1 (AC->T sequential + bevacizumab) or stratum 2 (TAC + bevacizumab). All HER2-positive participants were assigned to stratum 3 (TCH + bevacizumab).

The study included a treatment period of 1 year, followed by a 2 year posttreatment survival follow-up period.

Tipo de estudo

Intervencional

Inscrição (Real)

214

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

  • Estados Unidos
    • New Jersey
      • Bridgewater, New Jersey, Estados Unidos, 08807
        • Sanofi-Aventis Administrative Office

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

The following information on clinical trials is provided for information purposes only to allow participants and physicians to have an initial discussion about the trial. This information is not intended to be complete information about the trial, to contain all considerations that may be relevant to potential participation in the trial, or to replace the advice of a personal physician or health professional.

Inclusion Criteria:

  • Women >/= 18 years of age.
  • Histologically proven breast cancer with an interval between definitive breast surgery that includes axillary lymph node (LN) dissection or axillary nodal evaluation and study registration of < 60 days. (Note: Cycle 1 of chemotherapy treatment may NOT be infused until > 28 days after the date of definitive breast surgery and the participant must be recovered from any clinically significant toxicity thereof.)
  • Definitive surgical treatment must be either mastectomy, or breast conserving surgery with axillary lymph node dissection (axillary lymph node evaluation can be either full axillary node dissection or sentinel LN evaluation followed by dissection if sentinel LN is positive) for operable breast cancer (pT1-4 [including inflammatory], pNO-3, and MO). Margins of resected specimen from definitive surgery must be histologically free of invasive adenocarcinoma and ductal carcinoma in-situ (DCIS). Lobular carcinoma in-situ does not count as a positive margin.
  • Subjects must be either lymph node-positive (pN1-3) or lymph node-negative (pN0) with high-risk features as determined by Investigator.

  • High-risk, lymph node-negative participants, (pN0) will be defined as subjects having invasive adenocarcinoma with either a negative sentinel node biopsy (pN0[sn]) OR negative lymph node dissection (pN0) disease AND tumor size > 2 cm or tumor size >/= 1 cm with at least one of the following factors:

    • negative estrogen receptor (ER) and negative progesterone receptor (PR) status
    • histologic and/or nuclear Grade 2-3; or
    • age < 35 years
  • HER2/neu positive or negative tumors are eligible. HER2 positivity must be documented by fluorescence in situ hybridization (FISH).
  • Estrogen and progesterone receptor status must be performed on the primary tumor prior to study entry. Results must be pending or known at the time of study entry.
  • Normal cardiac function must be confirmed by left ventricular ejection fraction (LVEF) or shortening fraction (multiple-gated acquisition [MUGA] scan or echocardiography respectively). The result must be greater than the lower limit of normal (LLN) for the institution.

  • Hematology evaluation within 2 weeks prior to study entry:

    • Absolute neutrophil count (ANC) >/= 1,500/μL
    • Platelets >/= 100,000/μL
    • Hemoglobin >/= 9 g/dL

  • Hepatic function evaluation within 2 weeks prior to study entry:

    • Total bilirubin </= ULN for the institution
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be in the acceptable range.
  • Complete staging work-up as follows: All subjects must have an appropriate radiographic evaluation, e.g., computed tomography (CT), positron emission tomography (PET)/CT, and/or (magnetic resonance imaging) MRI of the brain, chest, abdomen and pelvis, and imaging of bone by either a bone scan or PET scan. In cases of positive bone imaging, a bone X-ray or MRI evaluation is mandatory to rule out the possibility of metastatic bone scan disease. Other tests may be performed as clinically indicated. It is recommended that all baseline staging should be completed within 35 days prior to study entry.

Exclusion Criteria:

  • Prior systemic anticancer therapy for breast cancer (immunotherapy, hormonotherapy, chemotherapy).
  • Prior anthracycline therapy, taxoids or platinum salts for any malignancy.
  • Prior radiation therapy for breast cancer or any radiotherapy to the chest wall for any other malignancy.
  • Bilateral invasive breast cancer.
  • Pregnant or lactating subjects
  • Cardiac disease or risk for same as judged by Investigator
  • Other serious illness or medical conditions such as (partial list- review with Investigator) history of significant neurologic or psychiatric disorders that would prohibit the understanding and giving of informed consent, active uncontrolled infection, active peptic ulcer, unstable diabetes mellitus or subjects with symptomatic, intrinsic lung disease resulting in dyspnea at rest
  • Current therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulators (SERMs), either for osteoporosis or prevention of breast cancer. Subjects must have discontinued these agents prior to study entry.
  • Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment must be stopped prior to study entry.
  • Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational non-marketed drug within 30 days prior to study entry.
  • Concurrent treatment with any other anti-cancer therapy.
  • Male subjects, as no clinical efficacy or safety data are available from phase I-II studies.
  • Chemotherapy and/or bevacizumab may not be given until > 7 days following a minor surgical procedure. Chemotherapy may be given without bevacizumab in circumstances in which the participant has recovered sufficiently to receive chemotherapy but has not yet reached a 28 day time point at which bevacizumab could be administered.

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: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Stratum 1 (AC->T + bevacizumab)

HER2-negative participants administered

  • doxorubicin and cyclophosphamide (AC) + bevacizumab for 4 cycles followed by
  • docetaxel (T) + bevacizumab for 4 cycles followed by
  • bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
Medicamento: Doxorubicin and cyclophosphamide (AC) + bevacizumab

For every 3-week cycle

  • bevacizumab 15 mg/kg infused intravenously (IV) on Day 1 followed by
  • doxorubicin 60 mg/m^2 IV push or infusion followed by cyclophosphamide 600 mg/m^2 IV push or infusion
  • Prophylactic G-CSF was administered within 24 hours following each cycle of chemotherapy but no greater than 72 hours after chemotherapy
Outros nomes:
  • Avastin® (bevacizumabe)
  • Adriamycin® (doxorubicin)
Medicamento: Docetaxel (T) + bevacizumab

For every 3-week cycle

  • bevacizumab 15 mg/kg infused intravenously (IV) on Day 1 followed by
  • docetaxel 100 mg/m^2 IV
  • Prophylactic G-CSF was administered within 24 hours following each cycle of chemotherapy but no greater than 72 hours after chemotherapy

Note: The starting dose of docetaxel was reduced to 75 mg/m^2 if toxicity occurred that met the criteria for doxorubicin dose reduction

Outros nomes:
  • Avastin® (bevacizumabe)
  • Taxotere® (docetaxel)
Medicamento: Bevacizumab maintenance therapy

- bevacizumab 15 mg/kg was infused IV

Treatment was every 3 weeks for 52 weeks from the date of the first administration regardless of the number of doses received or missed.

Outros nomes:
  • Avastin® (bevacizumabe)
Experimental: Stratum 2 (TAC + bevacizumab)

HER2-negative participants administered

  • docetaxel, doxorubicin, cyclophosphamide (TAC) + bevacizumab for 6 cycles followed by
  • bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
Medicamento: Bevacizumab maintenance therapy

- bevacizumab 15 mg/kg was infused IV

Treatment was every 3 weeks for 52 weeks from the date of the first administration regardless of the number of doses received or missed.

Outros nomes:
  • Avastin® (bevacizumabe)
Medicamento: Docetaxel, doxorubicin, cyclophosphamide (TAC) + bevacizumab

For every 3-week cycle

  • bevacizumab 15 mg/kg infused intravenously (IV) on Day 1 followed by
  • doxorubicin 50 mg/m^2 IV push or infusion followed by cyclophosphamide 500 mg/m^2 IV push or infusion followed by docetaxel 75 mg/m^2
  • Prophylactic G-CSF was administered within 24 hours following each cycle of chemotherapy but no greater than 72 hours after chemotherapy
Outros nomes:
  • Avastin® (bevacizumabe)
  • Taxotere® (docetaxel)
Experimental: Stratum 3 (TCH + bevacizumab)

All HER2-positive participants administered

  • docetaxel, carboplatin, trastuzumab (TCH) + bevacizumab for 6 cycles followed by
  • bevacizumab and trastuzumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed
Medicamento: Docetaxel, carboplatin, trastuzumab (TCH) + bevacizumab

For every 3-week cycle

  • bevacizumab 15 mg/kg infused intravenously (IV) on Day 1 followed by
  • docetaxel in 75 mg/m^2 IV followed by carboplatin AUC 6 mg/mL/min IV followed by
  • trastuzumab 6 mg/kg by IV infusion (For the first cycle 1 only a loading dose of trastuzumab 8 mg/kg IV was infused on Day 2)
  • Prophylactic G-CSF was administered within 24 hours following each cycle of chemotherapy but no greater than 72 hours after chemotherapy
Outros nomes:
  • Avastin® (bevacizumabe)
  • Taxotere® (docetaxel)
  • Herceptin® (trastuzumab)
Medicamento: Bevacizumab and trastuzumab maintenance therapy
  • bevacizumab 15 mg/kg was infused IV followed by
  • trastuzumab 6 mg/kg IV

Treatment was every 3 weeks for 52 weeks from the date of the first administration regardless of the number of doses received or missed.

Outros nomes:
  • Avastin® (bevacizumabe)
  • Herceptin® (trastuzumab)

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Cardiac Safety - Number of Participants With Grade 3-4 Clinical Congestive Heart Failure (CHF)
Prazo: from the first dose of study medication up to the end of follow-up (up to 3 yrs)

Participants were evaluated for clinical CHF every 3 weeks during chemotherapy, every 3 months while on maintenance therapy, and every 3 months during the 2-year follow-up period. Left ventricular ejection fraction (LVEF) of CHF was assessed by multi-gated acquisition (MUGA) or echocardiogram (ECHO) performed midway through completion of chemotherapy according to a treatment-specific schedule, every 12 weeks during maintenance therapy, and at 6 and 24 months after completion of maintenance therapy.

Grade 3-4 CHF were identified through a clinical review of all study collected investigator verbatim and the Medical Dictionary for Regulatory Activities (MedDRA). The preferred terms (PT) cardiac failure congestive, cardiomyopathy, and ejection fraction decreased were associated with CHF.
from the first dose of study medication up to the end of follow-up (up to 3 yrs)

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Safety - Number of Participants With Adverse Events (AE)
Prazo: from the administration of the first dose of study medication up to 30 days after the last dose of study medication; events ongoing at the time of discontinuation were monitored in the follow-up period until resolution.

An adverse event was any untoward medical occurrence in a participant of the clinical investigation, regardless of the relationship to study treatment.

A serious adverse event (SAE) was an AE that at any dose (including overdose) resulted in death, was life-threatening, required inpatient hospitalization or prolonged existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly/birth defect, and/or was medically important.

Treatment-emergent adverse events (TEAE) were defined as AEs that developed or worsened in severity during the on-treatment period.
from the administration of the first dose of study medication up to 30 days after the last dose of study medication; events ongoing at the time of discontinuation were monitored in the follow-up period until resolution.
Disease-free Survival (DFS) Rate
Prazo: from the administration of the first-dose of study medication up to 12 months, 18 months and 24 months

DFS was defined as the time from the administration of the first-dose of study medication until recurrence of tumor or death from any cause in the absence of previous documentation of tumor recurrence. DFS rate was the probability of being disease free and alive at a particular time. DFS rates were estimated using Kaplan-Meier Method, and 95% confidence intervals were computed using the method of Kalbfleisch and Prentice.

For participants who did have objective recurrence of tumor and who were still on study at the time of an analysis, or who were given antitumor treatment other than the study treatment, or who were removed from study follow-up prior to documentation of the tumor recurrence, DFS was censored at the last date the participant was known to be disease-free.
from the administration of the first-dose of study medication up to 12 months, 18 months and 24 months

Colaboradores e Investigadores

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

Patrocinador

Sanofi

Investigadores

  • Diretor de estudo: Vicki Erickson, MSN, Sanofi

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 agosto de 2006

Conclusão Primária (Real)

1 de outubro de 2011

Conclusão do estudo (Real)

1 de outubro de 2011

Datas de inscrição no estudo

Enviado pela primeira vez

16 de agosto de 2006

Enviado pela primeira vez que atendeu aos critérios de CQ

16 de agosto de 2006

Primeira postagem (Estimativa)

17 de agosto de 2006

Atualizações de registro de estudo

Última Atualização Postada (Estimativa)

14 de setembro de 2012

Última atualização enviada que atendeu aos critérios de controle de qualidade

16 de agosto de 2012

Última verificação

1 de janeiro de 2012

Mais Informações

Termos relacionados a este estudo

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • DOCET_L_00714

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

Pesquisar ensaios semelhantes

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

CROs by country

CROs in Saint Lucia

Condições

Doenças Raras

Intervenções de drogas

Suplementos Alimentares

Patrocinador / Colaboradores

Localizações

3
Se inscrever