Phase 1b/2 Study of BKM120 Plus Trastuzumab in Patients With HER2-positive Breast Cancer
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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Liege, Bélgica, 4000
- Novartis Investigative Site
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Wilrijk, Bélgica, 2610
- Novartis Investigative Site
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Catalunya
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Barcelona, Catalunya, España, 08035
- Novartis Investigative Site
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Hospitalet de LLobregat, Catalunya, España, 08907
- Novartis Investigative Site
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Comunidad Valenciana
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Valencia, Comunidad Valenciana, España, 46010
- Novartis Investigative Site
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Alabama
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Birmingham, Alabama, Estados Unidos, 35294-0006
- University of Alabama at Birmingham/ Kirklin Clinic Univ AL - PI
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Arkansas
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Fayetteville, Arkansas, Estados Unidos, 72703
- Highlands Oncology Group Dept of Highlands Oncology Grp
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Florida
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Tampa, Florida, Estados Unidos, 33612
- H. Lee Moffitt Cancer Center & Research Institute
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Michigan
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Detroit, Michigan, Estados Unidos, 48201
- Karmanos Cancer Institute Dept.of KarmanosCancerInst (6)
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Missouri
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St. Louis, Missouri, Estados Unidos, 63110
- Washington University School Of Medicine-Siteman Cancer Ctr WA Siteman
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New York
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New York, New York, Estados Unidos, 10003
- Beth Israel Medical Center BIMC
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37203
- Sarah Cannon Research Institute Sarah Cannon Cancer Center SC
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Lyon Cedex, Francia, 69373
- Novartis Investigative Site
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Saint-Herblain Cédex, Francia, 44805
- Novartis Investigative Site
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CA
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Cagliari, CA, Italia, 09134
- Novartis Investigative Site
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MC
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Macerata, MC, Italia, 62100
- Novartis Investigative Site
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MO
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Modena, MO, Italia, 41100
- Novartis Investigative Site
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TR
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Terni, TR, Italia, 05100
- Novartis Investigative Site
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Nottingham, Reino Unido, NG5 1PB
- Novartis Investigative Site
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Oxford, Reino Unido, OX3 7LJ
- Novartis Investigative Site
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East Sussex
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Brighton, East Sussex, Reino Unido, BN2 5BE
- Novartis Investigative Site
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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 de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: HER2+ metastatic breast cancer
Patients with HER2-overexpressing metastatic breast cancer, with or without PIK3 signaling pathway alteration, who have previously failed trastuzumab
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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.
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).
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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
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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.
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).
1000 mg/m2 twice a day from day 1 to Day 14 of a 21-day cycle.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Dose Limiting Toxicity (DLT) - Phase l Only
Periodo de tiempo: cycle 1 - 28 days
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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.
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cycle 1 - 28 days
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Overall Response Rate (ORR) - Phase ll
Periodo de tiempo: 18 months
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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
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Disease Control Rate (DCR) Based on Investigator Assessment- Phase l & ll
Periodo de tiempo: 18 months
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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
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Clinical Benefit Rate (CBR) - Phase l & ll
Periodo de tiempo: 18 months
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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
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Progression Free Survival (PFS) - Based on Investigator Review Using Kaplan Meier - Phase l & ll
Periodo de tiempo: 18 months
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18 months
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Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- CBKM120X2107
- 2009-015417-46 (Número EudraCT)
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