- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00248521
17-Dimethylaminoethylamino-17-Demethoxygeldanamycin (17-DMAG) in Treating Patients With Metastatic Solid Tumors or Tumors That Cannot Be Removed By Surgery
A Cancer Research UK Phase I Trial to Evaluate the Safety, Tolerability and Pharmacokinetics of 17-Dimethylaminoethyl-amino-17-Demethoxygeldanamycin (17-DMAG) Given as a Once Weekly Infusion in Patients With Advanced Solid Tumors
RATIONALE: Drugs used in chemotherapy, such as 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This phase I trial is studying the side effects and best dose of 17-DMAG in treating patients with metastatic solid tumors or tumors that cannot be removed by surgery.
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
OBJECTIVES:
Primary
- Determine the maximum tolerated dose, dose-limiting toxicity, and recommended phase II dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in patients with unresectable or metastatic solid tumors.
- Determine the feasibility, safety, and toxicity profile of this drug in these patients.
Secondary
- Determine the clinical pharmacokinetic profile of this drug in these patients.
- Determine tumor response in patients treated with this drug.
- Determine the biologically effective dose.
OUTLINE: This is an open-label, non-randomized, dose-escalation, multicenter study.
Patients receive 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) IV over 1 hour on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of 17-DMAG 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. An additional 10 patients are treated at the MTD.
After completion of study treatment, patients are followed for 28 days.
PROJECTED ACCRUAL: Approximately 25-35 patients will be accrued for this study within 12-18 months.
Tipo de estudio
Inscripción (Anticipado)
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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England
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Sutton, England, Reino Unido, SM2 5PT
- Royal Marsden - Surrey
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Sutton, England, Reino Unido, SM2 5NG
- Institute of Cancer Research - Sutton
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Northern Ireland
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Belfast, Northern Ireland, Reino Unido, BT8 8JR
- Belfast City Hospital Trust Incorporating Belvoir Park Hospital
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed solid tumor
- Unresectable or metastatic disease
- Standard curative or palliative measures do not exist OR are no longer effective OR patient refused such measures
- No known brain metastases
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-1
Life expectancy
- More than 12 weeks
Hematopoietic
- Absolute neutrophil count > 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 9.0 g/dL
Hepatic
- Bilirubin normal
- ALT and AST ≤ 1.5 times upper limit of normal
- No chronic liver disease
- Hepatitis B or C negative
Renal
- Creatinine normal OR
- Creatinine clearance normal
Cardiovascular
- No symptomatic New York Heart Association class III-IV cardiac disease
- No myocardial infarction within the past year
- No active ischemic heart disease within the past year
- No poorly controlled angina
- No uncontrolled dysrhythmia or dysrhythmias requiring antiarrhythmic drugs
- No transient ischemic attack
- No stroke
- No peripheral vascular disease
- No congenital long QT syndrome
- No history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
- QTc < 450 msec (for men) and 470 msec (for woman)
- LVEF > 40% by MUGA
- No left bundle branch block
Pulmonary
No symptomatic pulmonary disease requiring medication, including any of the following:
- Dyspnea with or without exertion
- Paroxysmal nocturnal dyspnea
- Oxygen requirement
- Significant pulmonary disease (e.g., chronic obstructive/restrictive pulmonary disease
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception 4 weeks before, during, and for 6 months after completion of study treatment
- No known HIV positivity
- No other malignancy within the past 5 years except adequately treated cone biopsied carcinoma in situ of the cervix or basal cell or squamous cell skin cancer
- No ongoing or active infection
- No diabetes mellitus (with evidence of severe peripheral vascular disease or ulcers)
- No psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled illness
PRIOR CONCURRENT THERAPY:
Biologic therapy
- More than 4 weeks since prior immunotherapy
- Concurrent epoetin alfa allowed
Chemotherapy
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- No prior 17-N-allylamino-17-demethoxygeldanamycin (17-AAG)
Endocrine therapy
- More than 4 weeks since prior endocrine therapy
- Concurrent luteinizing hormone-releasing hormone analogues for androgen-insensitive prostate cancer and rising prostate-specific antigen allowed
Radiotherapy
- More than 4 weeks since prior radiotherapy (except for palliative treatment)
- No prior irradiation field that potentially included the heart (e.g., mantle)
Surgery
- Not specified
Other
- Recovered from all prior therapy
- Concurrent bisphosphonates allowed
- At least 5 half-lives since prior and no concurrent medication that prolong QTc
- No other concurrent anticancer or investigational agents
- No concurrent grapefruit juice
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Enmascaramiento: Ninguno (etiqueta abierta)
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
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Recommended phase II dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) at 28 days after treatment
|
Medidas de resultado secundarias
Medida de resultado |
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Heat shock protein 90 (HSP90) client protein and co-chaperone changes up to 29 days after treatment
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Tumor response by RECIST criteria every 6 weeks while on study
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Clinical pharmacokinetic profile established during the first course of treatment
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Silla de estudio: Ian R. Judson, MA, MD, FRCP, Institute of Cancer Research, United Kingdom
Publicaciones y enlaces útiles
Publicaciones Generales
- Pacey SC, Wilson RH, Walton M, et al.: A phase I trial of the heat shock protein 90 (HSP90) inhibitor alvespimycin (17-dimethylaminoethylamino-17-demethoxygeldanamycin 17-DMAG) administered weekly, intravenously, to patients with advanced solid tumors. [Abstract] American Association for Cancer Research: Molecular Targets and Cancer Therapeutics, October 22-26, 2007, San Francisco, CA A-PR-6, 2007.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Anticipado)
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
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- ICR-PH1/102
- CDR0000442402 (Identificador de registro: PDQ (Physician Data Query))
- NCI-6547
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