- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT01499121
Study of Efficacy and Safety of Sunitinib Given on an Individualized Schedule
A Phase II, Multi-Centre, Study of the Efficacy and Safety of Sunitinib Given on an Individualized Schedule as First-Line Therapy for Metastatic Renal Cell Cancer
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
This is a single-arm, single-stage phase II study investigating the use of an individualized dosing regimen of Sunitinib on patients with metastatic renal cell carcinoma. The intent is to maximize dose intensity of sunitinib and minimize time off therapy based on individual tolerability using protocol directed dose modification criteria. Dose and schedule changes are done if toxicity (hematological, fatigue, skin, GI) is > grade 2. There will be no dosing or schedule changes for hypertension, hypothyroidism, skin color changes, heartburn, etc. unless clinically indicated. Subjects will continue therapy until progression according to RECIST 1.1 criteria. All subjects will be followed for progression free survival until progression but after 2 years on therapy, only grade 3/4 drug related adverse events will be recorded.
Fact-G and FKSI-DRS will be used to evaluate PRO/QOL at baseline and every 2 months timepoints. A more detailed pharmacokinetic blood sampling will be done in a subset of patients in an effort to understand if Sunitinib blood concentration has a tendency to go down during treatment, as has been shown to be the case for Sorafenib. Biomarker and genomics blood sampling for correlation with progression free survival, toxicity and pharmacokinetics will be collected at baseline and stored.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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Alberta
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Calgary, Alberta, Canadá, T2N 4N2
- Tom Baker Cancer Centre
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Edmonton, Alberta, Canadá, T6G 1Z2
- Cross Cancer Institute
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British Columbia
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Vancouver, British Columbia, Canadá, V5Z 4E6
- BC Cancer Agency - Vancouver
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Manitoba
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Winnipeg, Manitoba, Canadá, R3E 0V9
- CancerCare Manitoba
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Nova Scotia
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Halifax, Nova Scotia, Canadá, B3H 3A7
- QEII Health Sciences Centre
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Ontario
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Hamilton, Ontario, Canadá, L8V 5C2
- Juravinski Cancer Centre
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Kingston, Ontario, Canadá, K7L 2V7
- Kingston General Hospital Research Institute
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London, Ontario, Canadá, N6A 4L6
- London Health Sciences Centre
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Oshawa, Ontario, Canadá, L1G 2B9
- Durham Regional Cancer Centre
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Ottawa, Ontario, Canadá, K1H 8L6
- Ottawa Hospital Cancer Centre
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Toronto, Ontario, Canadá, M4N 3M5
- Sunnybrook Health Sciences Centre
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Toronto, Ontario, Canadá, M5G 2M9
- Princess Margaret Hospital
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Quebec
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Montreal, Quebec, Canadá, H2W 1T8
- Notre-Dame Hospital
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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 locally recurrent or metastatic renal cell carcinoma of clear cell origin or with a component of clear cell histology.
- Patients with nephrectomy (partial or total) or without nephrectomy are eligible.
- Evidence of measurable disease by RECIST criteria version 1.1.
- Male or female, age ≥ 18 years old
- Karnofsky performance status ≥ 80 %.
- Adequate organ functions determined by protocol directed lab values
- Subject's willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Exclusion Criteria:
- Renal cell carcinoma without any clear (conventional) cell component.
- Prior systemic therapy of any kind for advanced RCC (including targeted therapy, immunotherapy, chemotherapy, hormonal, or investigational therapy). Prior neo-adjuvant or adjuvant therapy with cytokines, IL-2 or vaccines is only permitted if it did not occur within the preceding 12 months. Prior and/or concurrent bisphosphonate therapy is allowed.
- Major surgery or radiation therapy within 4 weeks of starting the study treatment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated
- NCI CTCAE Version 3.0 grade 3 haemorrhage within 4 weeks of starting the study treatment
- Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell carcinoma, squamous cell skin cancer, or in situ cervical cancer
- Known brain metastases, spinal cord compression, or evidence of symptomatic brain or leptomeningeal carcinomatosis on screening CT or MRI scan.
- Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism
- Ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 grade ≥2
- Prolonged QTc interval on baseline EKG (>450 msec for males or >470 msec for females).
- Atrial Fibrillation of any grade.
- Uncontrolled hypertension (>150/100 mm Hg despite optimal medical therapy.
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection.
- Concurrent treatment on another clinical trial. Supportive care trials or non-treatment trials, e.g. QOL, and imaging trials are allowed.
- Concomitant treatment with a drug having proarrhythmic potential
- Use of potent CYP3A4 inhibitors and inducers 7 and 12 days before dosing, respectively
- Pregnancy or breastfeeding. Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. All female subjects with reproductive potential must have a negative pregnancy test (serum) prior to enrolment. Male subjects must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study
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 |
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Otro: Sunitinib
Starting dose/schedule of Sunitinib 50 mg/28 days on, 14 days off.
The intent is to maximize dose intensity of Sunitinib and minimize time off therapy based on individual tolerability using dose modification criteria.
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The starting dose will be 50 mg Sunitinib on the 28/14 schedule.
In patients that develop ≥ grade-2 toxicity after 2 weeks, therapy will be held for 7 days or resolution before continuing therapy according to the 1st dose/schedule change.
In patients that do not develop ≥ grade-2 toxicity, therapy will continue for 1-2 weeks or until ≥ grade-2 toxicity.
In patients that develop > grade-2 toxicity after less than 4 weeks, therapy will be held for 7 days or before continued according to the 1st dose/schedule change.
Patients that do develop grade-2 toxicity (but no more) on the 50 mg 28/14 schedule, will remain on schedule but the time off therapy will be reduced to 7 days if toxicity has resolved after a 7-day break.
Patients that develop ≤ grade-1 toxicity on the 50 mg 28/14 schedule, will be dose escalated according to protocol.
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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Progression free survival for sunitinib given on an individualized dose/schedule
Periodo de tiempo: 3.5 years
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Primary objective is to characterize the progression free survival for sunitinib given on an individualized dose/schedule in patients on first-line treatment for metastatic renal cell cancer.
Subjects will continue therapy until progression according to RECIST criteria version 1.1.
Tumour measurements using physical exam, spiral CT scan and/or MRI or other appropriate techniques deemed suitable by the investigator will be performed at screening and repeated at the end of every 2 cycles until disease progression.
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3.5 years
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Patient tolerability and safety of an individualized dose/schedule
Periodo de tiempo: 3.5 years
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To evaluate the tolerability and safety of individualized dose/schedule changes and dose escalation and schedule modification in patients with minimal toxicity after treatment with sunitinib 50 mg for 28 days.
The adverse effects of the drug will be assessed from adverse events, vital signs and by clinically significant changes in the lab evaluations and ECG's.
Categorical endpoints, will be summarized using proportions and frequencies.
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3.5 years
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Dose intensity of sunitinib given on an individualized dose/schedule.
Periodo de tiempo: 3.5 years
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The intent is to maximize dose intensity of sunitinib and minimize time off therapy based on individual tolerability using the dose modification criteria outlined in the protocol.
Dose and schedule changes are done if toxicity (hematological, fatigue, skin, GI) is > NCI CTCAE (version 3) grade 2. Patients that tolerate the standard 50 mg 28 days on/14 days off schedule with minimal toxicity (grade 1) will be dose escalated in 12.5 mg increments as outlined in the protocol on a schedule of 14 days on and 7 days off to a maximum of 75 mg.
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3.5 years
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Overall survival and patient quality of life
Periodo de tiempo: 3.5 years
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To characterize the overall survival and study the quality of life in subjects given sunitinib on an individualized dose/schedule.
Quality of life questionnaires (ie.
FACT-G and FKSI-DRS) will be completed at baseline and every 2 months thereafter until disease progression.
Summary scores for QOL outcomes will be reported as the raw value at each time point evaluated, as well as the change in score from baseline.
Overall survival will be calculated from the date of registration and estimated using the Kaplan-Meier method.
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3.5 years
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Georg A. Bjarnason, MD, Sunnybrook Health Sciences Centre
Publicaciones y enlaces útiles
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 (Actual)
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
- Neoplasias por tipo histológico
- Neoplasias
- Neoplasias Urológicas
- Neoplasias urogenitales
- Neoplasias por sitio
- Enfermedades Renales
- Enfermedades urológicas
- Adenocarcinoma
- Carcinoma
- Neoplasias Glandulares y Epiteliales
- Neoplasias Renales
- Carcinoma De Célula Renal
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Inhibidores de enzimas
- Agentes antineoplásicos
- Inhibidores de la angiogénesis
- Agentes moduladores de la angiogénesis
- Sustancias de crecimiento
- Inhibidores del crecimiento
- Inhibidores de la proteína quinasa
- Sunitinib
Otros números de identificación del estudio
- OZM-042
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. .
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