- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00027027
Safety Study of rhuMAb 2C4 to Treat Advanced Solid Tumors
A Phase I, Open-Label, Multicenter, Dose-Escalation Study of the Safety and Pharmacokinetics of a Recombinant Humanized Antibody to Her2 (rhuMAb 2C4) Administered Every 3 Weeks to Subjects With Advanced Solid Malignancies
Descripción general del estudio
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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California
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Los Angeles, California, Estados Unidos, 90211
- Cedars-Sinai Medical Center
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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:
- Signed informed consent
- Age >=18 years old
- ECOG performance status of 0 or 1 (see Appendix F)
- Life expectancy of >=12 weeks
- Histologically documented, incurable, locally advanced or metastatic solid malignancies
- Disease progression on or after standard effective therapy or a malignancy for which there is no standard therapy
- At least one bi-dimensionally measurable lesion (>=2 cm [>=1 cm on spiral CT scan])
- HER2-negative status as defined by fluorescence in situ hybridization (FISH) testing (only for subjects with breast cancer)
- Use of an effective means of contraception for women of childbearing potential
- Granulocyte count of >=1500/uL, platelet count of >=100,000/uL, and hemoglobin of >=9 g/dL
- Serum bilirubin less than or equal to the upper limit of normal (ULN) and alkaline phosphatase, AST, and ALT <=2.5x ULN (ALT and AST <=5x ULN for subjects with liver metastases; alkaline phosphatase <=5x ULN for subjects with liver or bone metastases)
- Serum creatinine less than or equal to ULN or creatinine clearance of >=60 mL/min
- International normalized ratio (INR) of <1.3 and activated partial thromboplastin time (aPTT) of <1.5x ULN
Exclusion Criteria:
- Pleural effusions, ascites, or bone lesions as the only manifestation of the current cancer
- Symptomatic or untreated brain metastases
- Prior chemotherapy, hormonal therapy (except for androgen-deprivation therapy for subjects with prostate cancer), radiotherapy, or immunotherapy within 4 weeks of Day 1 (within 6 weeks for nitrosoureas or mitomycin)
- Prior treatment with Herceptin
- Prior cumulative doxorubicin dose of >360 mg/m2 or the equivalent
- History of other malignancies within 5 years of Day 1 except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer
- History of significant cardiac disease, unstable angina, congestive heart failure, myocardial infarction, or ventricular arrhythmia requiring medication
- Ejection fraction of <50% or below the lower limit of normal determined by ECHO (Subjects who are unable to have ejection fraction evaluated by ECHO may have ejection fraction evaluated by a MUGA scan, although this must be discussed with the Medical Monitor prior to enrollment.)
- Active infection requiring IV antibiotics
- Uncontrolled hypercalcemia (>11.5 mg/dL)
- Clinically important history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
- Known human immunodeficiency virus (HIV) infection
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications
- Major surgery or significant traumatic injury within 3 weeks of Day 1
- Pregnancy or lactation
- Inability to comply with study and follow-up procedures
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Number of Participants With an Adverse Event (AE), Serious Adverse Event (SAE), or Death
Periodo de tiempo: Days 1, 2, 5, 8, and 15 of Cycle 1; Days 1, 8, and Week 3, of Cycles 2 and beyond up to 1 year and at the follow-up visit (4 weeks after last infusion)
|
For this protocol, an AE is defined any untoward medical occurrence (e.g., sign, symptom, disease, syndrome, intercurrent illness, abnormal laboratory finding) that emerges or worsens relative to pretreatment baseline during the treatment or post-treatment periods, regardless of the suspected cause. For this protocol an SAE was defined as any AE that occurred at any dose if:
The primary cause of death for all reported cases was disease progression, and all of the deaths occurred following study discontinuation, with one death occurring within 4 weeks of the last treatment day. |
Days 1, 2, 5, 8, and 15 of Cycle 1; Days 1, 8, and Week 3, of Cycles 2 and beyond up to 1 year and at the follow-up visit (4 weeks after last infusion)
|
Number of Participants With Dose-Limiting Toxicities (DLTs)
Periodo de tiempo: Day 1 of Cycles 1 and 2, and 24 hours after Cycle 2 infusion
|
Incidence of DLTs defined as any Grade 3 or 4 major organ toxicity according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 2 or any subjectively intolerable toxicity felt by the investigator to be related to rhuMAb 2C4. One participant in the 15.0 mg/kg dose group experienced a gastrointestinal hemorrhage on Day 16. This event was judged by the investigator to be related to study drug. The participant recovered in 3 days and continued to receive rhuMAb 2C4 beyond Cycle 2.This was the only DLT reported during the first two treatment cycles. |
Day 1 of Cycles 1 and 2, and 24 hours after Cycle 2 infusion
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Pharmacokinetic Measurement of Area Under the Curve (AUC)
Periodo de tiempo: Days 1 (predose, 89 minutes following start of infusion and at 1.5, 4, and 8 hours postdose) 2, 5, 8 and 15 of Cycle 1; Days 1 (predose and 29 minutes following start of infusion) and 8 of Cycle 2
|
Mean rhuMAb 2C4 serum concentrations versus nominal time profiles for the first two treatment cycles are presented for AUC micrograms per milliliters (ug/mL) by day.
A one-compartment model was used for the 0.5 mg/kg dose group, and a two-compartment model was used for the 2-15 mg/kg dose groups.
|
Days 1 (predose, 89 minutes following start of infusion and at 1.5, 4, and 8 hours postdose) 2, 5, 8 and 15 of Cycle 1; Days 1 (predose and 29 minutes following start of infusion) and 8 of Cycle 2
|
Pharmacokinetic Measurement of Systemic Clearance (CL)
Periodo de tiempo: Days 1 (predose, 89 minutes from infusion start, at 1.5, 4, and 8 hours postdose), 2, 5, 8 and 15 of Cycle 1; Days 1 (predose, 29 minutes from infusion start) and 8 of Cycles 2 and beyond until the follow-up visit (4 weeks after the last infusion)
|
A one-compartment model was used for the 0.5 mg/kg dose group, and a two-compartment model was used for the 2-15 mg/kg dose groups.
|
Days 1 (predose, 89 minutes from infusion start, at 1.5, 4, and 8 hours postdose), 2, 5, 8 and 15 of Cycle 1; Days 1 (predose, 29 minutes from infusion start) and 8 of Cycles 2 and beyond until the follow-up visit (4 weeks after the last infusion)
|
Pharmacokinetic Measurement of Volume of Central Compartment (Vc)
Periodo de tiempo: Days 1 (predose, 89 minutes from infusion start, at 1.5, 4, and 8 hours postdose), 2, 5, 8 and 15 of Cycle 1; Days 1 (predose, 29 minutes from infusion start) and 8 of Cycles 2 and beyond until the follow-up visit (4 weeks after the last infusion)
|
A one-compartment model was used for the 0.5 mg/kg dose group, and a two-compartment model was used for the 2-15 mg/kg dose groups.
|
Days 1 (predose, 89 minutes from infusion start, at 1.5, 4, and 8 hours postdose), 2, 5, 8 and 15 of Cycle 1; Days 1 (predose, 29 minutes from infusion start) and 8 of Cycles 2 and beyond until the follow-up visit (4 weeks after the last infusion)
|
Pharmacokinetic Measurement of Steady-State Volume of Distribution (Vss)
Periodo de tiempo: Days 1 (predose, 89 minutes from infusion start, at 1.5, 4, and 8 hours postdose), 2, 5, 8 and 15 of Cycle 1; Days 1 (predose, 29 minutes from infusion start) and 8 of Cycles 2 and beyond until the follow-up visit (4 weeks after the last infusion)
|
A one-compartment model was used for the 0.5 mg/kg dose group, and a two-compartment model was used for the 2-15 mg/kg dose groups.
|
Days 1 (predose, 89 minutes from infusion start, at 1.5, 4, and 8 hours postdose), 2, 5, 8 and 15 of Cycle 1; Days 1 (predose, 29 minutes from infusion start) and 8 of Cycles 2 and beyond until the follow-up visit (4 weeks after the last infusion)
|
Pharmacokinetic Measurement of Initial Distribution Half-Life (t1/2 Initial)
Periodo de tiempo: Days 1 (predose, 89 minutes from infusion start, at 1.5, 4, and 8 hours postdose), 2, 5, 8 and 15 of Cycle 1; Days 1 (predose, 29 minutes from infusion start) and 8 of Cycles 2 and beyond until the follow-up visit (4 weeks after the last infusion)
|
A one-compartment model was used for the 0.5 mg/kg dose group, and a two-compartment model was used for the 2-15 mg/kg dose groups.
|
Days 1 (predose, 89 minutes from infusion start, at 1.5, 4, and 8 hours postdose), 2, 5, 8 and 15 of Cycle 1; Days 1 (predose, 29 minutes from infusion start) and 8 of Cycles 2 and beyond until the follow-up visit (4 weeks after the last infusion)
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Pharmacokinetic Measurement of Terminal Half-Life (t1/2 Terminal) in Days
Periodo de tiempo: Days 1 (predose, 89 minutes from infusion start, at 1.5, 4, and 8 hours postdose), 2, 5, 8 and 15 of Cycle 1; Days 1 (predose, 29 minutes from infusion start) and 8 of Cycles 2 and beyond until the follow-up visit (4 weeks after the last infusion)
|
A one-compartment model was used for the 0.5 mg/kg dose group, and a two-compartment model was used for the 2-15 mg/kg dose groups.
|
Days 1 (predose, 89 minutes from infusion start, at 1.5, 4, and 8 hours postdose), 2, 5, 8 and 15 of Cycle 1; Days 1 (predose, 29 minutes from infusion start) and 8 of Cycles 2 and beyond until the follow-up visit (4 weeks after the last infusion)
|
Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (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
- TOC2297g
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 rhuMAb 2C4
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Hoffmann-La RocheTerminadoCáncer de mamaAustralia, España, Reino Unido, Alemania, Bélgica, Italia, Finlandia, Países Bajos
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Genentech, Inc.Terminado
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Genentech, Inc.Terminado
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Hoffmann-La RocheTerminado
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Hoffmann-La RocheTerminadoTumor solidoReino Unido, Países Bajos
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City of Hope Medical CenterNational Cancer Institute (NCI)Activo, no reclutandoCáncer de mama HER2 positivo | Cáncer de mama en estadio IV | Cáncer de mama en estadio IIIA | Cáncer de mama en estadio IIIB | Cáncer de mama en estadio IIA | Cáncer de mama en estadio IIB | Cáncer de mama en estadio IIIC | Cáncer de mama recurrente | Adenocarcinoma de mama | Carcinoma de mama inflamatorioEstados Unidos
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University of WashingtonUnited States Department of DefenseReclutamientoCáncer de mama anatómico en estadio I AJCC v8 | Cáncer de mama anatómico en estadio IA AJCC v8 | Cáncer de mama en estadio anatómico IB AJCC v8 | Cáncer de mama anatómico en estadio II AJCC v8 | Cáncer de mama anatómico en estadio IIA AJCC v8 | Cáncer de mama en estadio anatómico IIB AJCC v8 | Cáncer... y otras condicionesEstados Unidos
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Genentech, Inc.TerminadoCáncer de ovarios | Cáncer de trompa de Falopio | Cáncer peritonealEstados Unidos
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National Cancer Institute (NCI)Activo, no reclutandoNeoplasia Sólida MalignaEstados Unidos
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Hoffmann-La RocheTerminadoCáncer de mamaEstados Unidos, Reino Unido, Francia, Italia, España, Pavo, Brasil, India