Decitabine With or Without Interferon Alfa-2b in Treating Patients With Unresectable or Metastatic Solid Tumors
Inhibition of DNA Methylation by 1-Hr Infusion of 5-aza-2'-Deoxycitidine (Decitabine) x 10 Days (M-F) With Escalating Doses of Sub-Q Pegylated (PEG) Interferon-alpha 2B (PEG-Intron): A Phase I Study With Molecular Correlates
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
PRIMARY OBJECTIVES:
I. To assess toxicities of decitabine plus escalating doses of pegylated interferon alfa-2b (PEG-Intron) in patients with metastatic solid tumor.
II. To identify the dose-limiting toxicity of decitabine in combination with escalating doses of pegylated interferon alfa-2b in these patients.
III. To identify the maximum tolerated dose of pegylated interferon alfa-2b in combination with decitabine in these patients.
SECONDARY OBJECTIVES:
I. To evaluate pretreatment and post-treatment blood and tumor samples to identify changes in global (genomic) DNA methylation.
II. To evaluate pretreatment and post-treatment blood, skin and tumor samples to identify changes in Mage-1 mRNA and protein expression, DNMT-1 levels (due to sequestration by 5-azacytidine), p53 induction (evidence of DNA damage response), as well as changes in levels of 2'5'-oligoadenylate synthesis, MxA and HLA class I as indicators of interferon response.
III. To evaluate complete and partial response rates in patients receiving decitabine in combination with escalating doses of pegylated interferon alfa-2b.
OUTLINE:
This is a dose-escalation study of pegylated interferon alfa-2b. Patients are assigned to 1 of 2 treatment groups.
GROUP 1 (control): Patients receive decitabine IV over 1 hour on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression after the first course of treatment may crossover to receive treatment in group 2.
GROUP 2: Patients receive decitabine as in group 1 and pegylated interferon alfa-2b subcutaneously on days 1, 8, 15, and 22.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample, normal skin, and tissue biopsy collection at baseline and periodically during study. Blood, normal skin, and tissue samples are analyzed for global (genomic) DNA methylation (gene-promoter methylation, gene and protein expression, p53 induction by DNA damage) and interferon levels by high-performance (pressure) liquid chromatography and PCR methylation assays, and for pharmacodynamic studies.
After completion of study treatment, patients are followed at 28 days and then every 3 months.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Nevada
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Las Vegas, Nevada, Estados Unidos, 89135
- Nevada Cancer Institute-Summerlin Campus
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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:
Biopsy-proven solid tumor
- Metastatic or unresectable disease
- Tumor amenable to biopsy
- No curative or more effective treatment for this disease exists, in the opinion of the investigator
- Measurable disease by scans as assessed by RECIST criteria
No untreated brain metastasis
- No longer receiving steroid therapy for previously treated brain metastasis
- Zubrod performance status of 0-2
- Bilirubin ≤ 1.5 times upper limit normal (ULN)
- SGOT or SGPT ≤ 2.5 times ULN (≤ 5 ULN if hepatic metastases present)
- Serum creatinine ≤ 1.5 times ULN
- Creatinine clearance ≥ 50 mL/min
- ANC > 1,500/μL
- Platelet count > 100,000/μL
- Hemoglobin > 9 g/dL (transfusion allowed)
- No NYHA class III-IV cardiac problems (e.g., congestive heart failure or myocardial infarction within the past 2 months)
- No severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease, or active uncontrolled infection [e.g., HIV])
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception during and for 3 months after completion of study therapy
- Willing to undergo biopsies
- No medical or psychological conditions that, in the opinion of the investigator, may preclude the patient's ability to tolerate or complete the treatment, or to grant reliable informed consent
- No other prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I, II, or III cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years
- No prior extensive pelvic irradiation or prolonged nucleoside analogue pretreatment
- At least 28 days since prior and no concurrent chemotherapy, radiotherapy, surgery, biological therapy, anticancer agent, or other investigational drug
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Comparador activo: Group 1 (chemotherapy)
Patients receive decitabine IV over 1 hour on days 1-5 and 8-12.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients whose disease is not responding after the first course may crossover to group 2.
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Estudios correlativos
Dado IV
Otros nombres:
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Experimental: Group 2 (chemotherapy and antineoplastic agent)
Patients receive decitabine as in group 1 and pegylated interferon alfa-2b subcutaneously on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
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Estudios correlativos
Dado IV
Otros nombres:
Given SC
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Toxicities as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Periodo de tiempo: Up to 28 days
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The type, frequency, and severity of each toxicity will be reported.
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Up to 28 days
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Dose-limiting toxicity (DLT) of pegylated interferon alfa-2b when given with decitabine as assessed by NCI CTCAE version 3.0
Periodo de tiempo: First 28-day course
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DLT is defined as grade III drug-related non hematologic and/or grade IV drug-related hematologic toxicity.
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First 28-day course
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Maximum-tolerated dose (MTD) of pegylated interferon alfa-2b when given with decitabine as assessed by NCI CTCAE version 3.0
Periodo de tiempo: First 28-day course
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The MTD will be the dose level where not more than 1 case of a specific grade III-IV drug-related toxicity is observed, and either 2+toxicities have been observed at the next highest dose level, or the maximum dose-level of PEG-Intron has been reached.
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First 28-day course
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Global (genomic) DNA methylation changes by high-performance liquid chromatography (HPLC)
Periodo de tiempo: Baseline to up to day 1 of course 2
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Repeated measures analysis of variance and other linear modeling techniques will be used.
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Baseline to up to day 1 of course 2
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Changes in expression of methylation-regulated genes in human biological tissues
Periodo de tiempo: Baseline to up to day 1 of course 2
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Repeated measures analysis of variance and other linear modeling techniques will be used.
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Baseline to up to day 1 of course 2
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Complete and partial response rates
Periodo de tiempo: Up to 1 year
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Up to 1 year
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Wolfram Samlowski, Nevada Cancer Institute-Summerlin Campus
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
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Agentes Antivirales
- Inhibidores de enzimas
- Antimetabolitos, Antineoplásicos
- Antimetabolitos
- Agentes antineoplásicos
- Factores inmunológicos
- Interferones
- Interferón-alfa
- Decitabina
- Interferón alfa-2
- Azacitidina
- Peginterferón alfa-2b
Otros números de identificación del estudio
- NCI-2009-00295 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
- CDR0000597624
- NVCI-0725
- NVCI 07-25 (Otro identificador: Nevada Cancer Institute-Summerlin Campus)
- 8224 (Otro identificador: CTEP)
- R21CA122270 (Subvención/contrato del NIH de EE. UU.)
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