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Phase 1b/2 Study of BKM120 Plus Trastuzumab in Patients With HER2-positive Breast Cancer

9 de agosto de 2016 atualizado por: Novartis Pharmaceuticals

A Phase Ib/II, Open Label, Multi-center Study Evaluating the Safety and Efficacy of BKM120 in Combination With Trastuzumab in Patients With Relapsing HER2 Overexpressing Breast Cancer Who Have Previously Failed Trastuzumab

This study will assess the safety and efficacy of BKM120 in combination with trastuzumab in patients with relapsing HER2 overexpressing breast cancer who have previously failed trastuzumab.

The study will further assess the safety and preliminary efficacy of BKM120 in combination with trastuzumab and capecitabine in patients with relapsing HER2 overexpressing breast cancer and brain metastases (BM) who have previously failed trastuzumab.

Visão geral do estudo

Status

Rescindido

Condições

Intervenção / Tratamento

Tipo de estudo

Intervencional

Inscrição (Real)

72

Estágio

  • Fase 2
  • Fase 1

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

  • Bélgica
      • Liege, Bélgica, 4000
        • Novartis Investigative Site
      • Wilrijk, Bélgica, 2610
        • Novartis Investigative Site
  • Espanha
    • Catalunya
      • Barcelona, Catalunya, Espanha, 08035
        • Novartis Investigative Site
      • Hospitalet de LLobregat, Catalunya, Espanha, 08907
        • Novartis Investigative Site
    • Comunidad Valenciana
      • Valencia, Comunidad Valenciana, Espanha, 46010
        • Novartis Investigative Site
  • Estados Unidos
    • Alabama
      • Birmingham, Alabama, Estados Unidos, 35294-0006
        • University of Alabama at Birmingham/ Kirklin Clinic Univ AL - PI
    • Arkansas
      • Fayetteville, Arkansas, Estados Unidos, 72703
        • Highlands Oncology Group Dept of Highlands Oncology Grp
    • Florida
      • Tampa, Florida, Estados Unidos, 33612
        • H. Lee Moffitt Cancer Center & Research Institute
    • Michigan
      • Detroit, Michigan, Estados Unidos, 48201
        • Karmanos Cancer Institute Dept.of KarmanosCancerInst (6)
    • Missouri
      • St. Louis, Missouri, Estados Unidos, 63110
        • Washington University School Of Medicine-Siteman Cancer Ctr WA Siteman
    • New York
      • New York, New York, Estados Unidos, 10003
        • Beth Israel Medical Center BIMC
    • Tennessee
      • Nashville, Tennessee, Estados Unidos, 37203
        • Sarah Cannon Research Institute Sarah Cannon Cancer Center SC
  • França
      • Lyon Cedex, França, 69373
        • Novartis Investigative Site
      • Saint-Herblain Cédex, França, 44805
        • Novartis Investigative Site
  • Itália
    • CA
      • Cagliari, CA, Itália, 09134
        • Novartis Investigative Site
    • MC
      • Macerata, MC, Itália, 62100
        • Novartis Investigative Site
    • MO
      • Modena, MO, Itália, 41100
        • Novartis Investigative Site
    • TR
      • Terni, TR, Itália, 05100
        • Novartis Investigative Site
  • Reino Unido
      • Nottingham, Reino Unido, NG5 1PB
        • Novartis Investigative Site
      • Oxford, Reino Unido, OX3 7LJ
        • Novartis Investigative Site
    • East Sussex
      • Brighton, East Sussex, Reino Unido, BN2 5BE
        • Novartis Investigative Site

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

Tudo

Descrição

Inclusion Criteria:

  • World Health Organization (WHO) Performance Status of ≤ 2
  • Patients with HER2+ breast cancer by local laboratory testing (immunohistochemistry [IHC] 3+ staining or fluorescence in situ hybridization [FISH] confirmation for IHC 2+ and 1+)

  • Documented tumor resistance to trastuzumab:

    • Recurrence while on trastuzumab or within 12 months since the last infusion for patients who received trastuzumab as adjuvant treatment
    • Progression while on or within 4 weeks since the last infusion of trastuzumab for patients who received trastuzumab for metastatic disease.

  • Documented evidence of progressive disease per Response Evaluation Criteria in Solid Tumors (RECIST) on trastuzumab-based therapy defined as:

    • Phase Ib: at any time before study entry
    • Phase II: within 16 weeks before date of first dosing

  • Received at least 1 but no more than 4 prior anit-HER2 based regimens including at least 1 regimen containing trastuzumab (adjuvant or neo-adjuvant trastuzumab will be considered as one prior regimen). HER2 directed therapies are defined as comprising trastuzumab, lapatinib, and trastuzumab-DM1 (T-DM1) only.

    • Phase II only: trastuzumab, T-DM1 or lapatinib must be part of the most recent line of therapy

  • Previous lines of cytotoxic chemotherapy:

    • Phase Ib: no more than 4 lines of cytotoxic chemotherapy
    • Phase II: no more than 3 lines of cytotoxic chemotherapy

Measurable disease:

  • Phase Ib: patient has at least one measurable lesion or non-measurable disease as defined per RECIST
  • Phase II: patient has at least one measureable lesion as defined per RECIST

|| Specific Inclusion Criteria for patients in BM cohorts:

  • Patient has evidence of progressing brain metastases and/or new metastatic brain lesion(s) without leptomeningeal disease.
  • Patient has received prior WBRT and/or SRS at at >28 and >/= 14 days, respectively, prior to starting study drug and the patient must have recovered from the side effects of the therapy
  • WHO performance status of </=1
  • PT INR </= 1.5
  • Any number of prior HER2-directed and cytotoxic regimens, and the most recent line may be any type of anti-neoplastic therapy

|| Exclusion Criteria:

  • Patients with untreated brain metastases
  • Patients with acute or chronic liver, renal disease or pancreatitis
  • Patients with any peripheral neuropathy ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade 2
  • Patients with a history of mood disorders or ≥ CTCAE grade 3 anxiety
  • Patient with clinical manifest diabetes mellitus or steroid-induced diabetes mellitus

|| Specific Exclusion Criteria for patients in BM cohorts

  • Prior treatment with capecitabine
  • Patient has known dihydropyrimidine dehydrogenase (DPD) deficiency
  • Patient is currently receiving treatment with EIAED
  • Other protocol-defined inclusion/exclusion criteria may apply

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: HER2+ metastatic breast cancer
Patients with HER2-overexpressing metastatic breast cancer, with or without PIK3 signaling pathway alteration, who have previously failed trastuzumab
Medicamento: BKM120
Buparlisib (BKM120) is the investigational drug. Burparlisib was supplied as 10 mg and 50 mg hard gelatin capsules. Buparlisib was dosed on a flat scale of mg/day and not adjusted to body weight or body surface area. Buparlisib capsules were packaged in high density polyethylene bottles with a plastic child resistant closure.
Medicamento: Trastuzumab
Trastuzumab was used in this study according to the local regulations in each participating country. A loading dose (4 mg/kg) of trastuzumab was administered (if required as assessed by the principal Investigator based on the timing of the last trastuzumab dose prior to enrollment) on Day -7 over 90 minutes, followed by weekly intravenous infusion of 2 mg/kg maintenance doses from Day 1 of Cycle 1 (over 30 minutes if the previous infusion was well tolerated).
Experimental: HER2+ metastatic breast cancer with BM
Patients with HER2-overexpressing metastatic breast cancer and brain metastases, with or without PIK3 signaling pathway alteration, who have previously failed trastuzumab
Medicamento: BKM120
Buparlisib (BKM120) is the investigational drug. Burparlisib was supplied as 10 mg and 50 mg hard gelatin capsules. Buparlisib was dosed on a flat scale of mg/day and not adjusted to body weight or body surface area. Buparlisib capsules were packaged in high density polyethylene bottles with a plastic child resistant closure.
Medicamento: Trastuzumab
Trastuzumab was used in this study according to the local regulations in each participating country. A loading dose (4 mg/kg) of trastuzumab was administered (if required as assessed by the principal Investigator based on the timing of the last trastuzumab dose prior to enrollment) on Day -7 over 90 minutes, followed by weekly intravenous infusion of 2 mg/kg maintenance doses from Day 1 of Cycle 1 (over 30 minutes if the previous infusion was well tolerated).
Medicamento: Capecitabine
1000 mg/m2 twice a day from day 1 to Day 14 of a 21-day cycle.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Dose Limiting Toxicity (DLT) - Phase l Only
Prazo: cycle 1 - 28 days
Determination of the maximum tolerated dose (MTD) in the dose escalation part of the study was based upon the estimation of the probability of DLT in Cycle 1 in patients of the dose-determining set.
cycle 1 - 28 days
Overall Response Rate (ORR) - Phase ll
Prazo: 18 months

Objective response rate (ORR) was defined as the rate of patients with best overall response (BOR) equal to complete response (CR) or partial response (PR) according to RECIST 1.0 from the Investigators review.

Per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0 assessed of the disease status by imaging (i.e. CT/MRI): Complete Response (CR) = Disappearance of all tumor lesions; Partial Response (PR)= >=30% shrinkage of lesions; Overall Response (OR) = patients with CR and PR.
18 months

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Disease Control Rate (DCR) Based on Investigator Assessment- Phase l & ll
Prazo: 18 months

Disease control rate (DCR) = patients with complete response (CR), partial response (PR) or stable disease (SD) as per RECIST criteria.

Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0 assessed the disease status by imaging (i.e. CT/MRI): CR = disappearance of all tumor lesions; PR = >=30% shrinkage of lesions; SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD); PD = At least a 20% increase in the sum of the longest diameter of all measured target lesions, taking as reference the smallest sum of longest diameter of all target lesions recorded at or after baseline.
18 months
Clinical Benefit Rate (CBR) - Phase l & ll
Prazo: 18 months

CBR = patients with CR, PR or SD ≥ 24 weeks according to RECIST by the investigator.

Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0 assessed the disease status by imaging (i.e. CT/MRI): CR = Disappearance of all tumor lesions; PR= >=30% shrinkage of lesions; SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD; PD = At least a 20% increase in the sum of the longest diameter of all measured target lesions, taking as reference the smallest sum of longest diameter of all target lesions recorded at or after baseline.
18 months
Progression Free Survival (PFS) - Based on Investigator Review Using Kaplan Meier - Phase l & ll
Prazo: 18 months
18 months

Colaboradores e Investigadores

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

Patrocinador

Novartis Pharmaceuticals

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 maio de 2010

Conclusão Primária (Real)

1 de agosto de 2014

Conclusão do estudo (Real)

1 de agosto de 2014

Datas de inscrição no estudo

Enviado pela primeira vez

7 de maio de 2010

Enviado pela primeira vez que atendeu aos critérios de CQ

27 de maio de 2010

Primeira postagem (Estimativa)

28 de maio de 2010

Atualizações de registro de estudo

Última Atualização Postada (Estimativa)

17 de agosto de 2016

Última atualização enviada que atendeu aos critérios de controle de qualidade

9 de agosto de 2016

Última verificação

1 de agosto de 2016

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • CBKM120X2107
  • 2009-015417-46 (Número EudraCT)

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 .

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