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

9 sierpnia 2016 zaktualizowane przez: 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.

Przegląd badań

Status

Zakończony

Warunki

Interwencja / Leczenie

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

72

Faza

  • Faza 2
  • Faza 1

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

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

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

18 lat i starsze (Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

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

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Nielosowe
  • Model interwencyjny: Zadanie dla jednej grupy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: HER2+ metastatic breast cancer
Patients with HER2-overexpressing metastatic breast cancer, with or without PIK3 signaling pathway alteration, who have previously failed trastuzumab
Lek: 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.
Lek: 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).
Eksperymentalny: 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
Lek: 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.
Lek: 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).
Lek: Capecitabine
1000 mg/m2 twice a day from day 1 to Day 14 of a 21-day cycle.

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Dose Limiting Toxicity (DLT) - Phase l Only
Ramy czasowe: 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
Ramy czasowe: 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

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Disease Control Rate (DCR) Based on Investigator Assessment- Phase l & ll
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 18 months
18 months

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Novartis Pharmaceuticals

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów

1 maja 2010

Zakończenie podstawowe (Rzeczywisty)

1 sierpnia 2014

Ukończenie studiów (Rzeczywisty)

1 sierpnia 2014

Daty rejestracji na studia

Pierwszy przesłany

7 maja 2010

Pierwszy przesłany, który spełnia kryteria kontroli jakości

27 maja 2010

Pierwszy wysłany (Oszacować)

28 maja 2010

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Oszacować)

17 sierpnia 2016

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

9 sierpnia 2016

Ostatnia weryfikacja

1 sierpnia 2016

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

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

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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