- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT01251874
Veliparib and Carboplatin in Treating Patients With HER2-Negative Metastatic Breast Cancer
A Phase 1 Dose-Escalation Study of ABT-888 (Veliparib) in Combination With Carboplatin in HER2 Negative Metastatic Breast Cancer
Descripción general del estudio
Estado
Condiciones
- Mutación del gen BRCA1
- Mutación del gen BRCA2
- Carcinoma de mama recurrente
- Receptor de estrógeno negativo
- Receptor de estrógeno positivo
- HER2/Neu Negativo
- Receptor de progesterona negativo
- Receptor de progesterona positivo
- Carcinoma de mama triple negativo
- Cáncer de mama en estadio IV AJCC v6 y v7
- Cáncer de mama en estadio IIIB AJCC v7
- Cáncer de mama en estadio IIIC AJCC v7
Descripción detallada
PRIMARY OBJECTIVES:
I. To determine the recommended phase II dose of veliparib along with carboplatin on a 14-day and 21-day schedule in patients with Her2 negative metastatic breast cancer that are estrogen receptor (ER)/progesterone receptor(PR) negative or ER and/or PR positive with defects in Fanconi Anemia (FA) pathway repair genes.
II. To determine the safety and tolerability of combining veliparib on a 14-day and 21-day schedule with carboplatin in this patient population.
III. To determine the preliminary efficacy of this combination in this patient population.
SECONDARY OBJECTIVES:
I. To determine the pharmacodynamic endpoints of poly(ADP-ribose) polymerase (PARP) inhibition in the tumor by using, A) 3'-[F-18]fluoro-3'-deoxythymidine positron emission tomography (FLT-PET) of the target lesions, B) circulating tumor cells to detect the induction of the histone variant gamma H2AX, and C) peripheral blood mononuclear cells to assess poly ADP-Ribose (PAR) levels.
II. To determine biomarkers in the primary tumor that may predict antitumor responses to PARP inhibition such as breast cancer 1/2, early onset (BRCA)1/2 protein, Fanconi anemia, complementation group D2 (FANCD2) nuclear foci formation and expression of micro-ribonucleic acid (RNA) 155 (miR 155).
OUTLINE: This is a dose-escalation study of veliparib.
Patients receive carboplatin intravenously (IV) over 1 hour on day 1 and veliparib orally (PO) twice daily (BID) on days 1-7 or 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 12 weeks.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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New York
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Bronx, New York, Estados Unidos, 10461
- Montefiore Medical Center-Einstein Campus
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Bronx, New York, Estados Unidos, 10467
- Montefiore Medical Center - Moses Campus
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Ohio
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Columbus, Ohio, Estados Unidos, 43210
- Ohio State University Comprehensive Cancer Center
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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:
Patients must have histologically or cytologically proven metastatic or locally advanced inoperable breast cancer that fulfills one of the following two criteria:
- Triple-negative breast cancer
- ER and/or PR positive, HER2 negative if their tumors have been shown to be deficient for the FA pathway, based on FA triple stain immunofluorescence (FATSI) screening
HER negative with a known germline BRCA1/2 mutation
- Patients with ER- and/or PR-positive breast cancer will be consented to have their existing, or to be obtained, paraffin-embedded tumor tissue screened for FA deficiency
- No more than 3 prior chemotherapy regimens for metastatic disease will be allowed; any number of prior hormone therapies will be allowed; however, at least 4 weeks should have elapsed since prior chemotherapy (6 weeks for mitomycin C and nitrosoureas and 2 weeks for hormone therapy) or radiation therapy (2 weeks for limited field palliative radiation to the bone)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Patients with treated brain metastases and life expectancy of greater than 3 months
- Patients with known Gilbert syndrome with abnormal unconjugated bilirubin will be eligible
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic acid transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
- Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- No prior therapy with veliparib for metastatic disease will be allowed
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
- Patients must be able to swallow pills
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib or other agents used in study
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with veliparib
- Known human immunodeficiency virus (HIV)-infected patients on protease inhibitors are ineligible; HIV-infected patients with adequate cluster of differentiation (CD)4 counts (> 500) and not on protease inhibitors are eligible
- Patients with active seizure or a history of seizures are not eligible
- Patients with uncontrolled central nervous system (CNS) metastasis are not eligible; patients with CNS metastases must be stable after therapy for > 3 months and off steroid treatment prior to study enrollment
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Experimental: Treatment (veliparib, F 18 fluorothymidine, carboplatin)
Patients receive carboplatin IV over 1 hour on day 1 and veliparib PO BID on days 1-7 or 1-14.
Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients may undergo fluorothymidine PET scan and peripheral blood cell and tumor tissue collection periodically for correlative studies.
|
Estudios correlativos
Dado IV
Otros nombres:
Estudios correlativos
Orden de compra dada
Otros nombres:
Estudios correlativos
Otros nombres:
Estudios correlativos
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Incidence of adverse events to measure the safety and tolerability of this treatment combination
Periodo de tiempo: Up to 12 weeks post-treatment
|
Number and severity of toxicity incidents will be tabulated.
Non-hematologic toxicities will be evaluated via the ordinal Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 standard toxicity grading.
Hematologic toxicity measures of thrombocytopenia, neutropenia and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization via CTCAE standard toxicity grading.
Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.
|
Up to 12 weeks post-treatment
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Clinical response (complete and partial response as well as stable and progressive disease)
Periodo de tiempo: Up to 12 weeks post-treatment
|
Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease.
Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors guideline (version 1.1).
|
Up to 12 weeks post-treatment
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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
PARP-1 activity
Periodo de tiempo: Up to 5 years
|
Analysis will be descriptive and exploratory in nature.
Potential relationships and differences will be explored using graphical analyses and quantitative summaries of this marker.
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Up to 5 years
|
Thymidine kinase uptake on 3'-[F-18]fluoro-3'-deoxythymidine positron emission tomography (FLT-PET) scans
Periodo de tiempo: Up to 18 weeks (after course 3)
|
Analysis will be descriptive and exploratory in nature.
Potential relationships and differences will be explored using graphical analyses and quantitative summaries of this marker.
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Up to 18 weeks (after course 3)
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Circulating tumor cell markers
Periodo de tiempo: Up to 5 years
|
Analysis will be descriptive and exploratory in nature.
Potential relationships and differences will be explored using graphical analyses and quantitative summaries of this marker.
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Up to 5 years
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Bhuvaneswari Ramaswamy, Ohio State University Comprehensive Cancer Center
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
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 (Actual)
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 por tipo histológico
- Neoplasias
- Neoplasias por sitio
- Neoplasias Glandulares y Epiteliales
- Enfermedades de los senos
- Neoplasias de mama
- Carcinoma
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Agentes Antivirales
- Inhibidores de enzimas
- Agentes antineoplásicos
- Inhibidores de poli(ADP-ribosa) polimerasa
- Carboplatino
- Veliparib
- Alovudina
Otros números de identificación del estudio
- NCI-2011-02552 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
- P30CA016058 (Subvención/contrato del NIH de EE. UU.)
- UM1CA186712 (Subvención/contrato del NIH de EE. UU.)
- U01CA076576 (Subvención/contrato del NIH de EE. UU.)
- 8609 (Otro identificador: CTEP)
- CDR0000688990
- OSU 10080
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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