Resumen

Este estudio evaluó la eficacia y la seguridad de RAD001 en primera línea seguido de sunitinib en segunda línea en comparación con la secuencia inversa: sunitinib en primera línea seguido de RAD001 en segunda línea, para el tratamiento de pacientes con carcinoma de células renales metastásico (CCRM).

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Patients with advanced renal cell carcinoma.
Patients with at least one measurable lesion.
Patients with a Karnofsky Performance Status ≥70%.
Adequate bone marrow function.
Adequate liver function.
Adequate renal function.
Left ventricular ejection fraction (LVEF) ≥ lower limit of institutional normal (LLN)
Women of childbearing potential must have had a negative serum pregnancy test within 14 days prior to the administration of the study medication. Adequate contraception must be used while on study.

Criterios de exclusión

Less than 4 weeks post-major surgery
Patients who had radiation therapy within 4 weeks prior to start of study treatment (palliative radiotherapy to bone lesions allowed within 2 weeks prior to study treatment start).
Patients in need for major surgical procedure during the course of the study
Patients with a serious non-healing wound, ulcer, or bone fracture
Patients with a history of seizure(s) not controlled with standard medical therapy
Patients who have received prior systemic treatment for their metastatic RCC
Patients who have previously received systemic mTOR inhibitors (sirolimus, temsirolimus, everolimus) or VEGF inhibitors. Note: History of adjuvant immunotherapy, vaccines or adjuvant sorafenib following localized surgical nephrectomy is acceptable.
Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins or to its excipients
Patients with a known hypersensitivity to sunitinib or its excipients
History or clinical evidence of central nervous system (CNS) metastases. Note: Subjects who have previously-treated CNS metastases (surgery plus or minus radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria are eligible:
Are asymptomatic and,
have had no evidence of active CNS metastases for ≥ 6 months prior to enrollment and,
have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC)
Clinically significant gastrointestinal abnormalities including, but not limited to:
Malabsorption syndrome
Major resection of the stomach or small bowel that could affect the absorption of study drug
Active peptic ulcer disease
Inflammatory bowel disease
Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation
History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
Poorly controlled hypertension \[defined as systolic blood pressure (SBP) of ≥160mmHg or diastolic blood pressure (DBP) of ≥ 95mmHg\]
Patients receiving chronic systemic treatment with corticosteroids or another immunosuppressive agent
Patients with a known history of HIV seropositivity.
Patients with active bleeding.
Patients who have any severe and/or uncontrolled medical conditions or other conditions within the past 12 months that could affect their participation in the study such as:
Cardiac angioplasty or stenting, unstable angina pectoris, symptomatic peripheral vascular disease, symptomatic congestive heart failure (NYHA II, III, IV), myocardial infarction ≤ 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia, cerebrovascular accidents ≤ 6 months before study treatment start.
Prolongation of corrected QT interval (QTc) \> 500 milliseconds (msecs).
Severally impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 0\^2 saturation that is 88% or less at rest on room air.
Poorly controlled diabetes as defined by fasting serum glucose \>2.0 x ULN.
Any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study.
Liver disease such as chronic active hepatitis or chronic persistent hepatitis.
History of cerebrovascular accident (CVA) including transient ischemic attack (TIA).
History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible.
Patients who have a history of another primary malignancy and off treatment for ≤ 3 years
Female patients of child-bearing potential who are not using adequate birth control methods, or who are pregnant or breast feeding.
Patients who are using other investigational agents or who had received investigational drugs ≤ 2 weeks prior to study treatment start.
Patients unwilling or unable to comply with the protocol.

Intervenciones

drug

everolimus

Everolimus was administered orally at 10 mg/day. Everolimus is formulated as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets.

drug

sunitinib

Sunitinib was administered orally 50 mg daily, on a schedule of 4 weeks on/2 weeks off. Sunitinib was supplied as hard gelatin capsules of 12.5 mg, 25 mg, or 50 mg strength according to local practice.

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

everolimus

sunitinib

Ubicaciones

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Patrocinadores