Irinotecan, Oxaliplatin, and Capecitabine in Treating Patients With Unresectable Solid Tumors
A Phase I And Pharmacogenetic Study Of CPT-11, Oxaliplatin, And Capecitabine In Patients With Solid Tumors
Descripción general del estudio
Estado
Descripción detallada
OBJECTIVES:
I. To define the maximally tolerated dose of the combination of CPT-11 (irinotecan hydrochloride), oxaliplatin, and capecitabine in three different populations, based on UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) genotype (6/6, 6/7, and 7/7).
II. To identify any activity of this treatment combination in patients with metastatic cancer.
III. To examine the differences in the toxicity profile, especially pertaining to hematologic and gastrointestinal (GI), and the maximally tolerated dose of the combination of CPT-11, oxaliplatin and capecitabine with respect to the UGT1A1 haplotypes.
IV. Examine the effect of the UGT1A1 genotype on the pharmacokinetics of CPT-11 and its metabolites.
OUTLINE: This is a dose-escalation study. Patients are stratified according to UGT1A1 genotype (6/6 vs 6/7 [closed to accrual as of 8/24/06] vs 7/7).
Patients receive irinotecan hydrochloride intravenously (IV) over 90 minutes and oxaliplatin IV over 2 hours on day 1 and capecitabine orally (PO) twice daily (QD) on days 2-15. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of irinotecan hydrochloride, oxaliplatin, and capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 6-10 patients (for a total of 12 patients) receive treatment at that dose.
After completion of study treatment, patients are followed up at 3 months.
PROJECTED ACCRUAL: A total of 54-84 patients (12-22 for stratum I, 18-28 for stratum II [closed to accrual as of 8/24/06], and 24-34 for stratum III) will be accrued for this study within approximately 4.4 years.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Minnesota
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Rochester, Minnesota, Estados Unidos, 55905
- Mayo Clinic
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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:
Histologically confirmed solid tumor for which there is no known standard therapy that is potentially curative or capable of extending life expectancy
- Unresectable disease
- Willing to provide biologic specimens to determine UGT1A1 genotype
No CNS metastases
- Prior CNS metastases allowed provided patient was treated with surgery and/or radiotherapy and is stable for more than 8 weeks
- Performance status - ECOG 0-2
- At least 12 weeks
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 9.0 g/dL
- Bilirubin no greater than upper limit of normal (ULN) for patients with 6/6 UGT1A1 genotype (1.5 times ULN for patients with 6/7 [closed to accrual as of 8/24/06] or 7/7 UGT1A1 genotype)
- AST no greater than 3 times ULN (5 times ULN if there is liver involvement)
- Creatinine no greater than 1.5 times ULN
- No New York Heart Association class III or IV heart disease
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No prior allergy to platinum compounds, irinotecan, or to antiemetics or antidiarrheals appropriate for administration with study therapy
- No uncontrolled infection
- No seizure disorder
- No peripheral neuropathy grade 2 or greater
- More than 4 weeks since prior biologic therapy
- More than 4 weeks since prior immunotherapy
- No concurrent immunotherapy
- No concurrent prophylactic colony-stimulating factor therapy
- More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
- No other concurrent chemotherapy
- See Disease Characteristics
- More than 4 weeks since prior radiotherapy
- No prior radiotherapy to more than 25% of the bone marrow
- No concurrent radiotherapy
- See Disease Characteristics
- No other concurrent investigational therapy
- No concurrent sorivudine, brivudine, lamivudine, or stavudine
- No concurrent enrollment in any other study involving a pharmacologic agent for symptom control or therapeutic intent
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: Arm I
Patients receive irinotecan hydrochloride IV over 90 minutes and oxaliplatin IV over 2 hours on day 1 and capecitabine PO QD on days 2-15.
Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
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Estudios correlativos
Dado IV
Otros nombres:
Estudios correlativos
Otros nombres:
Orden de compra dada
Otros nombres:
Dado IV
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
|---|---|
|
MTD defined as one dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) assessed using NCI CTCAE v3.0
Periodo de tiempo: 3 weeks
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3 weeks
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Tiempo hasta cualquier toxicidad relacionada con el tratamiento
Periodo de tiempo: Hasta 3 meses
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Se resumirán de forma descriptiva.
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Hasta 3 meses
|
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Tiempo hasta toxicidad grado 3+ relacionada con el tratamiento
Periodo de tiempo: Hasta 3 meses
|
Se resumirán de forma descriptiva.
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Hasta 3 meses
|
|
Tiempo de progresión
Periodo de tiempo: Hasta 3 meses
|
Se resumirán de forma descriptiva.
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Hasta 3 meses
|
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Tiempo hasta el fracaso del tratamiento
Periodo de tiempo: Desde el registro hasta la documentación de progresión, toxicidad inaceptable o negativa a continuar con la participación del paciente, evaluado hasta 3 meses
|
Se resumirán de forma descriptiva.
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Desde el registro hasta la documentación de progresión, toxicidad inaceptable o negativa a continuar con la participación del paciente, evaluado hasta 3 meses
|
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Incidence of UTG1A1*28 polymorphism
Periodo de tiempo: Up to 3 months
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The overall incidence of UTG1A1*28 polymorphism will be estimated and summarized in this patient population.
In addition, the incidence of this polymorphism will be explored in relation to tumor type.
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Up to 3 months
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Adverse events profile assessed using NCI CTCAE v3.0
Periodo de tiempo: Up to 3 months
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The number and severity of all adverse events (overall, by dose level, and by tumor group) will be tabulated and summarized for the three patient groups.
The grade 3+ adverse events will also be described and summarized in a similar fashion.
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Up to 3 months
|
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Toxicity profile assessed using NCI CTCAE v3.0
Periodo de tiempo: Up to 3 months
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Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized in each of the two groups.
Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
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Up to 3 months
|
|
Response profile using RECIST criteria
Periodo de tiempo: Up to 3 months
|
Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as table and progressive disease in the two patient populations (overall and by tumor group).
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Up to 3 months
|
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Time until hematologic nadirs (WBC, ANC, platelets)
Periodo de tiempo: Up to 3 months
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Will be summarized descriptively.
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Up to 3 months
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Colaboradores e Investigadores
Patrocinador
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
Otros números de identificación del estudio
- NCI-2012-01444
- MC0311
- NCI-6240
- CDR0000344367
- MAYO-MC0311
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