- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT01281150
Veliparib in Combination With Carboplatin and Paclitaxel in Treating Patients With Locally Advanced or Metastatic Solid Tumors
A Phase 1 Study of ABT-888 (Veliparib) in Combination With Weekly Carboplatin and Paclitaxel in Advanced Solid Tumors
Descripción general del estudio
Estado
Condiciones
- Cáncer de mama en estadio IV
- Carcinoma de mama recurrente
- Cáncer de mama en estadio IIIB
- Cáncer de mama en estadio IIIC
- Receptor de estrógeno negativo
- Receptor de estrógeno positivo
- HER2/Neu Negativo
- Receptor de progesterona negativo
- Carcinoma de mama triple negativo
- Carcinoma de mama masculino
- Neoplasia sólida del adulto
Descripción detallada
PRIMARY OBJECTIVE:
I. To determine the maximum-tolerated dose (MTD) of the combination of weekly carboplatin, paclitaxel, and veliparib.
SECONDARY OBJECTIVES:
I. To assess the safety, tolerability, and MTD of the combination of weekly carboplatin, paclitaxel, and veliparib.
II. To assess the safety and toxicity of this combination as determined by the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v. 4.0) and to determine the dose-limiting toxicity (DLT).
III. To determine the pharmacokinetic and pharmacodynamic effects of this combination, including determinations of poly (adenosine diphosphate [ADP]-ribose) polymerase (PAR) in tumor specimens when available, assessment of deoxyribonucleic acid (DNA) damage as measured by gamma H2A histone family, member X (g-H2AX) in skin biopsies and tumor specimens will be obtained.
IV. To assess characteristics of primary tumor specimens that may contribute to efficacy of this combination including breast cancer, early onset (BRCA) by immunohistochemistry, gene analysis of PARP 1, PARP 2, BRCA, and triple negative and homologous recombination repair (HRR) deficiency gene expression signatures.
V. To document any anti-tumor response.
OUTLINE: This is a dose-escalation study of veliparib.
DOSE-ESCALATION: Patients receive veliparib orally (PO) twice daily (BID) on days 1-5, 8-12, and 15-19 and paclitaxel IV over 1 hour and carboplatin IV over 30 minutes in course 1 and 3 hours in subsequent courses on days 3, 10, and 17. After 4 courses, patients receive paclitaxel and carboplatin on days 3 and 10 only. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (Completed as of 12/2012)
EXPANSION COHORT: Patients receive veliparib PO BID on days 1-21 and paclitaxel IV over 1 hour and carboplatin IV over 3 hours on days 3 and 10. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up for 4 weeks.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
Pennsylvania
-
Hershey, Pennsylvania, Estados Unidos, 17033-0850
- Penn State Milton S Hershey Medical Center
-
Pittsburgh, Pennsylvania, Estados Unidos, 15213
- UPMC-Magee Womens Hospital
-
Pittsburgh, Pennsylvania, Estados Unidos, 15232
- University of Pittsburgh Cancer Institute (UPCI)
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
Histologically or cytologically confirmed solid tumor that has evidence of metastatic spread (stage IV) or is locally advanced and unresectable
- Patients with breast cancer may have estrogen receptor positive or negative (ER+ or ER-) disease
- Patients with breast cancer may not be human epidermal growth receptor -2 (HER2)-positive ( 3+), or fluorescent in situ hybridization (FISH) ratio > 2.2
Patients in the biopsy expansion cohort must have "triple negative" breast cancer defined as:
- Estrogen receptor staining < 10%; progesterone receptor staining <10%; Her 2 < 2.2 by FISH, or immunohistochemistry (IHC) 0-2+
Patients may have been previously treated
- In the dose escalation cohort, there is no limit to prior therapies
- In the expansion cohort, patients may have only had 1-3 prior regimens for metastatic disease
Patients may have received prior carboplatin, paclitaxel, or poly (ADP-ribose) polymerase (PARP) inhibitor therapy as part of their previous treatment regimens
- However, patients may NOT have received prior therapy with paclitaxel, carboplatin, and PARP inhibitor in combination
- Patients must not have received chemotherapy within 4 weeks of starting study (or 6 weeks if prior treatment was with carmustine [BCNU] or mitomycin C)
- Patients must not have received radiation within 2 weeks of starting study
- Eastern Cooperative Oncology Group (ECOG) performance status (PS)< 2 (Karnofsky > 60%)
- Life expectancy > 2 months
- Absolute neutrophil count (ANC) >= 1,500/mcL
- Platelet count >= 100,000/mcL
- Total bilirubin =< 1.5 times upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times ULN
- Creatinine normal within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73m^2 for patients with creatinine levels above institutional normal
- Must able to swallow pills
Pregnant women are excluded from this study
- 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 enrolled in the expanded cohort with mandatory biopsies must:
- Have accessible tumors
- Not be on therapeutic anticoagulation
- Have signed informed consent form
Exclusion Criteria:
- Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) or radiotherapy within 2 weeks (4 weeks for central nervous system [CNS] metastases) 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
- Concurrent treatment with bisphosphonates, or other bone anti-resorptive agent such as denosumab is allowed; concurrent treatment with hormonal therapy (tamoxifen, ovarian suppression with gonadotropin-releasing hormone [GNRH] agonists, aromatase inhibitors) or trastuzumab therapy is NOT allowed in breast cancer patients; prostate cancer patients may continue GNRH agents
- 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
- Active seizure or history of seizure disorder
- Patients with CNS metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for > 3 months and must be off steroid treatment prior to study enrollment
- Patients who undergo biopsy as part of the study in the expanded dose cohort should not be on anti-coagulants or have a pre-existing coagulopathy
- Peripheral neuropathy of severity greater than grade 1
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, paclitaxel, carboplatin)
DOSE-ESCALATION: Patients receive veliparib PO twice daily BID on days 1-5, 8-12, and 15-19 and paclitaxel IV over 1 hour and carboplatin IV over 30 minutes in course 1 and 3 hours in subsequent courses on days 3, 10, and 17. After 4 courses, patients receive paclitaxel and carboplatin on days 3 and 10 only. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (Completed as of 12/2012) EXPANSION COHORT: Patients receive veliparib PO BID on days 1-21 and paclitaxel IV over 1 hour and carboplatin IV over 3 hours on days 3 and 10. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
Estudios correlativos
Dado IV
Otros nombres:
Estudios correlativos
Dado IV
Otros nombres:
Orden de compra dada
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
---|---|
MTD defined as the dose level one level below the lowest dose where greater than or equal to 2 patients experience a DLT assessed by National Cancer Institute (NCI) CTCAE v. 4.0
Periodo de tiempo: 21 days
|
21 days
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Change in BRCA protein levels by immunohistochemistry
Periodo de tiempo: Baseline to day 4 of course 2
|
Calculated and compared using the Wilcoxon rank sum test.
|
Baseline to day 4 of course 2
|
Change in PAR and g-H2AX in tumor tissue
Periodo de tiempo: Baseline to day 4 of course 2
|
Assessed with Wilcoxon signed rank tests.
|
Baseline to day 4 of course 2
|
Grade >= 3 non-hematological or any grade 5 DLTs as graded by the NCI CTCAE v. 4.0
Periodo de tiempo: 21 days
|
Statistics on the number of cycles received by patients and any dose reductions will be tabulated.
|
21 days
|
Incidence of adverse events as graded by the NCI CTCAE v. 4.0
Periodo de tiempo: Up to 4 weeks post-treatment
|
The maximum grade of toxicity for each category of interest will be recorded for each patient and the summary results will be tabulated by category and grade.
|
Up to 4 weeks post-treatment
|
Plasma concentration of carboplatin, paclitaxel, and veliparib using liquid chromatography-mass spectrometry (LC-MS) assay and spectrometry assay
Periodo de tiempo: Baseline, at 30 minutes and at 1, 2, 4, and 8 hours on day 3 of course 1
|
Baseline, at 30 minutes and at 1, 2, 4, and 8 hours on day 3 of course 1
|
|
Response complete response [Cr], partial response [PR], and stable disease [SD]) using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
Periodo de tiempo: Up to 4 weeks post-treatment
|
CR, PR, and incidence of SD will be tabulated by disease diagnosis and by dose level.
|
Up to 4 weeks post-treatment
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Shannon Puhalla, University of Pittsburgh Cancer Institute (UPCI)
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (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 por tipo histológico
- Neoplasias
- Neoplasias por sitio
- Neoplasias Glandulares y Epiteliales
- Enfermedades de los senos
- Neoplasias de mama
- Carcinoma
- Neoplasias Mamarias Masculinas
- Mecanismos moleculares de acción farmacológica
- Inhibidores de enzimas
- Agentes antineoplásicos
- Moduladores de tubulina
- Agentes antimitóticos
- Moduladores de mitosis
- Agentes antineoplásicos, fitogénicos
- Inhibidores de poli(ADP-ribosa) polimerasa
- Carboplatino
- Paclitaxel
- Paclitaxel unido a albúmina
- Veliparib
Otros números de identificación del estudio
- NCI-2011-02490 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
- U01CA099168 (Subvención/contrato del NIH de EE. UU.)
- P30CA047904 (Subvención/contrato del NIH de EE. UU.)
- CDR0000693333
- 09-084 (Otro identificador: University of Pittsburgh Cancer Institute (UPCI))
- 8620 (Otro identificador: CTEP)
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. .
Ensayos clínicos sobre Cáncer de mama en estadio IV
-
Charite University, Berlin, GermanyKlinikum rechts der Isar, TU München, (TUM), Munich, Germany.ReclutamientoSarcoma | Cancer de prostata | Cáncer de páncreas en estadio IV | Etapa IV del cáncer de mama | Carcinoma de células escamosas | Melanoma Etapa IVAlemania
-
Sidney Kimmel Comprehensive Cancer Center at Johns...National Cancer Institute (NCI)TerminadoCáncer de próstata en estadio IVEstados Unidos
-
Burzynski Research InstituteRetiradoCáncer de próstata en estadio IVEstados Unidos
-
Tianjin Medical University Cancer Institute and...Peking University First Hospital; The Affiliated Nanjing Drum Tower Hospital... y otros colaboradoresDesconocidoCáncer de próstata en estadio IVPorcelana
-
Seoul National University HospitalNational Cancer Center, Korea; Chonbuk National University Hospital; Asan Medical... y otros colaboradoresTerminadoCáncer de pulmón en estadio IV | Cáncer de páncreas en estadio IV | Cáncer de mama en estadio IV | Tumor cerebral pediátrico | Cáncer de colon en estadio IV | Cáncer gástrico en estadio IV | Cáncer de hígado en estadio IV | Neoplasia hematológica maligna | Tumor sólido pediátrico | Linfoma pediátrico | Metastásico... y otras condicionesCorea, república de
-
Jerome Canady, M.D.Activo, no reclutandoCáncer de pulmón en estadio IV | Cáncer de vejiga en estadio IV | Cáncer de páncreas en estadio IV | Neoplasia sólida maligna recurrente | Cáncer de mama en estadio IV | Cáncer de células renales en estadio IV | Cáncer de próstata en estadio IV | Cáncer de colon en estadio IV | Cáncer de recto en estadio... y otras condicionesEstados Unidos
-
National Cancer Institute (NCI)TerminadoAdenocarcinoma de próstata | Cáncer de próstata en estadio IVEstados Unidos
-
Spanish Oncology Genito-Urinary GroupPivotal S.L.Activo, no reclutandoCáncer de próstata en estadio III | Cáncer de próstata en estadio IV
-
Zhou FuxiangAún no reclutandoCáncer de páncreas en estadio IV | Carcinoma hepatocelular, colangiocarcinomaPorcelana
-
City of Hope Medical CenterNational Cancer Institute (NCI)TerminadoCáncer de próstata en estadio III | Cáncer de próstata en estadio IVEstados Unidos
Ensayos clínicos sobre Análisis de biomarcadores de laboratorio
-
ORIOL BESTARDTerminadoTrasplante de riñón | Infección por CMVEspaña, Bélgica
-
Vanderbilt University Medical Center4DMedicalTerminado
-
Central and North West London NHS Foundation TrustBritish HIV Association (BHIVA)Aún no reclutandoInfecciones por VIH | Hepatitis B
-
Johns Hopkins UniversityReclutamiento
-
University of MiamiActivo, no reclutando
-
Hvidovre University HospitalElsassFondenTerminadoAcidosis metabólica del recién nacidoDinamarca
-
Rio de Janeiro State UniversityCoordenação de Aperfeiçoamento de Pessoal de Nível Superior.; Conselho Nacional... y otros colaboradoresTerminadoEnfermedades cardiovasculares | Deficiencia de vitamina D | Condiciones relacionadas con la menopausiaBrasil