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

9. august 2016 opdateret af: 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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

72

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

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

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: HER2+ metastatic breast cancer
Patients with HER2-overexpressing metastatic breast cancer, with or without PIK3 signaling pathway alteration, who have previously failed trastuzumab
Medicin: 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.
Medicin: 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).
Eksperimentel: 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
Medicin: 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.
Medicin: 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).
Medicin: Capecitabine
1000 mg/m2 twice a day from day 1 to Day 14 of a 21-day cycle.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Dose Limiting Toxicity (DLT) - Phase l Only
Tidsramme: 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
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Disease Control Rate (DCR) Based on Investigator Assessment- Phase l & ll
Tidsramme: 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
Tidsramme: 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
Tidsramme: 18 months
18 months

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Novartis Pharmaceuticals

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. maj 2010

Primær færdiggørelse (Faktiske)

1. august 2014

Studieafslutning (Faktiske)

1. august 2014

Datoer for studieregistrering

Først indsendt

7. maj 2010

Først indsendt, der opfyldte QC-kriterier

27. maj 2010

Først opslået (Skøn)

28. maj 2010

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

17. august 2016

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

9. august 2016

Sidst verificeret

1. august 2016

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

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

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Metastatisk brystkræft

Kliniske forsøg med BKM120

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in Paraguay

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

Abonner