A Phase I Trial of 17-Allylaminogeldanamycin (17-AAG) in Solid Tumor and Lymphoma Patients
tanespimycin
Enfermedad Crónica+24
+ Infecciones por virus ADN
+ Enfermedades Hematológicas
Estudio de Tratamiento
Resumen
Fecha de inicio: 1 de agosto de 1999
Fecha en la que se inscribió al primer participante.OBJECTIVES: Determine the maximum tolerated dose and dose-limiting toxicity of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), administered at 2 different dosing schedules, in patients with unresectable solid tumors. Determine the pharmacokinetics of this drug in these patients. Assess the effect of this drug on heat shock protein chaperone complex components and client proteins in lymphoma tissue obtained pre- and post-treatment in patients with relapsed lymphoma. Determine any response to this drug in these patients. OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 treatment groups. Group I: Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Group II: Patients receive 17-AAG IV over 1 hour on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 1-6 solid tumor patients receive escalating doses of 17-AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 10 patients with either lymphoma or superficial solid tumors accessible for biopsy are treated as in group II at the MTD. Patients are followed for 3 months. PROJECTED ACCRUAL: A total of 58-130 patients (30-72 for group I and 28-58 for group II) will be accrued for this study within 2 years.
Protocolo
Esta sección proporciona detalles del plan del estudio, incluyendo cómo está diseñado y qué se está evaluando.Estudio de Tratamiento
Elegibilidad
Los investigadores buscan pacientes que cumplan ciertos criterios, conocidos como criterios de elegibilidad: estado general de salud o tratamientos previos.Cualquier sexo
Sexo biológico de los participantes elegibles para inscribirse.A partir de 18 años
Rango de edades de los participantes que pueden unirse al estudio.Voluntarios sanos no permitidos
Indica si personas sanas, sin la condición que se estudia, pueden participar.Condiciones
Patología
Criterios
DISEASE CHARACTERISTICS: One of the following diagnoses: Histologically or cytologically confirmed solid tumor* Unresectable disease Hodgkin's or non-Hodgkin's lymphoma Relapsed disease Failed at least 1 prior therapy Neoplastic cells are accessible through biopsy NOTE: *Only patients with biopsy-accessible superficial tumors or lymphoma are eligible once the maximum tolerated dose has been determined No known standard therapy that is potentially curative or definitely capable of extending life expectancy exists No CNS metastases PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 12 weeks Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9 g/dL Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN) AST no greater than 2.5 times ULN Alkaline phosphatase no greater than 2 times ULN (5 times ULN if liver involvement) Renal: Creatinine no greater than 1.25 times ULN OR Creatinine clearance at least 60 mL/min Cardiovascular: No New York Heart Association class III or IV heart disease Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective nonhormonal contraception No uncontrolled infection No seizure disorder No history of serious allergic reaction to eggs PRIOR CONCURRENT THERAPY: Biologic therapy: More than 4 weeks since prior immunotherapy More than 4 weeks since prior biologic therapy No concurrent immunotherapy No concurrent routine or prophylactic use of a colony-stimulating factor (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) Chemotherapy: More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered from acute and reversible toxic effects No other concurrent chemotherapy Endocrine therapy: No concurrent birth control pills No concurrent steroids as anti-emetics Radiotherapy: More than 4 weeks since prior radiotherapy No prior radiotherapy to more than 25% of the bone marrow No prior radiopharmaceuticals No concurrent radiotherapy Surgery: Not specified Other: No concurrent 3A4 enzyme inhibitors (e.g., verapamil, erythromycin, miconazole, or ketoconazole) No concurrent investigational ancillary therapy No concurrent enrollment in another study involving a pharmacologic agent (e.g., drugs, biologics, immunotherapy approaches, or gene therapy) for symptom control or therapeutic intent
Centros del Estudio
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