- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT01042925
Study of XL147 (SAR245408) in Combination With Trastuzumab or Paclitaxel and Trastuzumab in Subjects With Metastatic Breast Cancer Who Have Progressed on a Previous Trastuzumab-based Regimen
A Phase 1/2 Study of XL147 (SAR245408) Administered in Combination With Trastuzumab or Paclitaxel and Trastuzumab in Subjects With Metastatic Breast Cancer Who Have Progressed on a Previous Trastuzumab-Based Regimen
Phase 1 of this study will evaluate the maximum tolerated dose (MTD) of XL147 when given in combination with trastuzumab (Herceptin) and in combination with trastuzumab and paclitaxel. After the MTD is established for each combination (Phase 2), subjects will be enrolled to evaluate the preliminary efficacy and safety of these combinations in metastatic HER2 positive breast cancer. Both trastuzumab and paclitaxel are used in the treatment of metastatic breast cancer (MBC), but patients can develop resistance.
The link between PI3K mutations and trastuzumab resistance has been seen in breast cancer patients. This suggests that inhibitors of the PI3K/PTEN pathway may have the potential to restore sensitivity to trastuzumab. Similarly, introduction of activated mutant forms of PI3K has been shown to transform and confer paclitaxel resistance to immortalized breast epithelial cells. XL147 is a potent and selective inhibitor of PI3K and inhibits phosphorylation of multiple downstream components of PI3K/PTEN signaling. Therefore, XL147 may have utility in the treatment of trastuzumab resistant/refractory and HER2-positive MBC when administered in combination with trastuzumab alone or with trastuzumab and paclitaxel.
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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Madrid, España, 28041
- Investigational Site Number 3413
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California
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Los Angeles, California, Estados Unidos, 90033
- Investigational Site Number 1537
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Florida
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Fort Meyers, Florida, Estados Unidos, 33901
- Investigational Site Number 1238
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02115
- Investigational Site Number 1138
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Michigan
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Detroit, Michigan, Estados Unidos, 48201
- Investigational Site Number 1330
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New York
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Bronx, New York, Estados Unidos, 10467
- Investigational Site Number 1151
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New York, New York, Estados Unidos, 10032
- Investigational Site Number 1150
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37203
- Investigational Site Number 1214
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Nashville, Tennessee, Estados Unidos, 37232
- Investigational Site Number 1246
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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:
- The subject has pathologically and radiologically confirmed metastatic HER2 positive breast cancer (Stage IV disease). Subjects must have received and progressed on at least one prior trastuzumab-containing regimen for metastatic disease. For subjects in Arm 2, they must also have received at least one prior taxane-containing regimen.
- The subject has at least one lesion that is not within a previously radiated field and measurable on computerized tomography (CT) or magnetic resonance imaging scan (MRI)
- The subjects enrolled in Phase 2 must be willing to undergo a biopsy of the primary tumor or a tumor metastasis at baseline, if tumor tissue is amenable to biopsy
- The subject's primary tumor and/or metastatic lesion must overexpress HER2
- For subjects enrolled in Phase 2: samples from archival or fresh tissue, or a tissue block of the subject's tumor.
- The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
- The subject has adequate organ and marrow function
- The subject is capable of understanding the informed consent and complying with the protocol and has signed the informed consent document prior to any study-specific screening procedures or evaluations being performed.
- Sexually active subjects must agree to use a medically-accepted barrier method of contraception during the course of the study and for 3 months following discontinuation of study treatments. For subjects using oral contraceptives, a barrier method must be used in addition to the oral contraceptive
- Subjects of childbearing potential must have a negative pregnancy test at screening and enrollment
Exclusion Criteria:
- The subject has previously been treated with a selective inhibitor of PI3K and / or AKT
- Certain restrictions on prior therapies apply
- The subject has not recovered from toxicity due to prior therapy to Grade ≤ 1 or to pre-therapy baseline
- The subject has untreated, symptomatic, or progressive brain metastases. Any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for ≥4 weeks prior to first study treatment
- The subject has prothrombin time/International Normalized Ratio (PT/INR) or partial thromboplastin time (PTT) test results at screening that are ≥ 1.3 times above the laboratory upper limit of normal
- The subject has a diagnosis of uncontrolled diabetes mellitus
- The subject has uncontrolled significant intercurrent illness
- The subject has uncontrolled hypertension or other clinically significant cardiovascular disease
- The subject has left ventricular ejection fraction (LVEF) ≤ 50%
- The subject has a baseline corrected QT interval ≥ 460 ms
- The subject is currently receiving anticoagulation with therapeutic doses of warfarin (low-dose warfarin ≤ 1mg/day is permitted)
- The subject is pregnant or breastfeeding
- The subject is known to be positive for the human immunodeficiency virus (HIV) (a test for HIV at screening is not required)
- The subject has any other diagnosis of malignancy or evidence of malignancy (except non-melanoma skin cancer, in situ carcinoma of the cervix) within 2 years prior to screening for this study
- The subject has a previously identified allergy or hypersensitivity or is intolerant to components of any of the study treatment formulations
- The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Arm 1
XL147 in combination with trastuzumab
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administered orally once daily as tablet(s)
administered by IV once every 3 weeks
Otros nombres:
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Experimental: Arm 2
XL147 in combination with trastuzumab and paclitaxel
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administered orally once daily as tablet(s)
administered by IV once every 3 weeks
Otros nombres:
administered by IV once every week
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
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Safety and tolerability of XL147 in combination with trastuzumab and in combination with trastuzumab and paclitaxel
Periodo de tiempo: safety assessments at weekly study visits
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safety assessments at weekly study visits
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In Phase 1, the maximum tolerated dose (MTD) of XL147 when administered in combination with trastuzumab and in combination with trastuzumab and paclitaxel
Periodo de tiempo: assessed by weekly study visits
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assessed by weekly study visits
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In Phase 2, objective tumor response
Periodo de tiempo: every 6 weeks
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every 6 weeks
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Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
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Duration of response and progression-free survival (Phase 2)
Periodo de tiempo: every 6 weeks
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every 6 weeks
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Pharmacokinetics and pharmacodynamics of XL147 and trastuzumab when given in combination, and of XL147, trastuzumab, and paclitaxel when given in combination
Periodo de tiempo: assessed weekly, then every 3 weeks
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assessed weekly, then every 3 weeks
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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
Términos MeSH relevantes adicionales
- Enfermedades de la piel
- Neoplasias
- Neoplasias por sitio
- Enfermedades de los senos
- Neoplasias de mama
- Mecanismos moleculares de acción farmacológica
- Agentes antineoplásicos
- Moduladores de tubulina
- Agentes antimitóticos
- Moduladores de mitosis
- Agentes antineoplásicos, fitogénicos
- Agentes antineoplásicos inmunológicos
- Paclitaxel
- Trastuzumab
Otros números de identificación del estudio
- ARD11439
- XL147-203 (Otro identificador: (other study code))
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
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Ensayos clínicos sobre XL147 (SAR245408)
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SanofiTerminadoNeoplasias Endometriales | Cáncer endometrialEstados Unidos, Bélgica
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SanofiTerminadoEstudio de seguridad y farmacocinética de XL147 (SAR245408) en adultos con tumores sólidos o linfomaLinfoma | CáncerEstados Unidos, España
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SanofiTerminadoTumores sólidosEstados Unidos
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SanofiTerminadoGlioblastoma | Astrocitoma, Grado IVEstados Unidos
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SanofiTerminadoCáncer | Cáncer de pulmón de células no pequeñas | Carcinoma endometrial | Carcinoma de ovarioEstados Unidos
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SanofiTerminado
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SanofiTerminadoNeoplasia malignaJapón
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SanofiTerminadoCáncer de mamaEstados Unidos, Francia, España
-
SanofiTerminadoNeoplasia malignaEspaña, Bélgica, Estados Unidos, Francia
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SanofiMerrimack PharmaceuticalsTerminadoCánceres de tumores sólidosEstados Unidos