Locally Advanced or Metastatic Renal Cell Carcinoma MedDRA version: 20.0 Level: PT Classification code 10050513 Term: Metastatic renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Cabometyx
Product Name: Cabometyx
Product Code: XL184
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: CABOZANTINIB
CAS Number: 849217-68-1
Concentration unit: mg milligram(s)
Sponsors
Fundación ONCOSUR
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet the following inclusion criteria: 1. Patients with locally advanced or metastatic renal cell carcinoma with a clear cell component confirmed histologically by biopsy. 2. Patients eligible for CN according to their surgical risk established in routine clinical practice at the center. 3. Age = 18 years. 4. Patients with an ECOG performance status of between 0 and 1. 5. Patients with appropriate organ and bone marrow function within 4 weeks prior to starting treatment with cabozantinib: o Leukocyte count > 4,000 cells/µL o Hemoglobin > 9 g/dL o Platelet count > 100,000/mm3 o Serum creatinine 30 mL/min (according to the Cockcroft-Gault formula (Cockcroft and Gault 1976). o Preserved liver function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Patients with a second active malignant tumor. 2. Patients with tumors treated in the last 2 years. 3. Pregnant or breast-feeding women. 4. Women of child-bearing potential who do not agree to use a contraceptive method during treatment. Women participating in the study should have undergone surgical sterilization, be post-menopausal, or agree to use a highly effective contraceptive method (in accordance with CTFG criteria) during the treatment period. Both patients of both sexes and their partners must use effective contraception during treatment and, at least, up to four months after completing treatment. Since oral contraceptives can not possibly be considered "effective contraceptive methods", they should be used in conjunction with another method, such as a barrier method. 5. Fertile men who do not agree to use a contraceptive method during treatment. Male participants in the study should have undergone surgical sterilization, or agree to use a highly effective contraceptive method (in accordance with CTFG criteria) during the treatment period. 6. Patients with gastrointestinal disorders, including: o Inability to take oral medication. o Need for parenteral nutrition. o Prior surgical procedures affecting absorption. o Active gastrointestinal bleeding. o Malabsorption syndrome. o Gastrointestinal disorders that increase the risk of perforation. 7. Patients who have had any of the following conditions within the 12 months prior to inclusion in the study: myocardial infarction, uncontrolled angina, uncontrolled hypertension, peripheral arterial or coronary graft bypass, congestive heart failure, stroke, or transient ischemic attack. 8. Patients with tumors that invade or affect major blood vessels, gastrointestinal tract, or trachea/bronchi. 9. Patients with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related diseases. 10. Patients with active hepatitis or hepatitis C. 11. Patients with active tuberculosis. 12. Patients with uncontrolled (Ca > 12 mg/dL) or symptomatic hypercalcemia who require continuous treatment with bisphosphonates or denosumab. 13. Patients who have undergone major surgery within 4 weeks prior to inclusion in the study. 14. Patients with active bleeding. 15. Patients with a recent episode of intestinal obstruction. 16. Patients who have previously received VEGF growth factor-targeted therapy for advanced disease. 17. Patients who have undergone radiation therapy for bone metastases within 2 weeks prior to the first dose of cabozantinib, or any external radiation therapy within 4 weeks prior to the first dose of cabozantinib. 18. Patients who have received an allogeneic transplant or stem cells in the last 5 years. 19. Malignant tumors within 3 years before Day 1 of Cycle 1, except for those with negligible risk of metastasis or death and who have been treated with curative intent, such as cervical carcinoma in situ or localized prostate cancer treated with curative intent. 20. Patients receiving therapeutic doses of oral anticoagulants (e.g., warfarin, direct thrombin inhibitors and Factor Xa) or antiplatelet agents (e.g., clopidogrel). The use of low molecular weight heparins is allowed. 21. Hypersensitivity to the active substance or to any of the excipients (exclude lactose intolerant patients since each film-coated tablet contains 46.61 mg of lactose) 22. Any other clinical condition that the physician responsible for the patient con
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effectiveness of preoperative treatment with cabozantinib (Cabometyx), measured by the radiological response rate prior to cytoreductive nephrectomy, in patients with advanced or metastatic renal cell carcinoma who are candidates for cytoreductive nephrectomy .;Secondary Objective: -To evaluate radiological response rates during treatment with cabozantinib in patients with advanced or metastatic renal cell carcinoma who are candidates for cytoreductive nephrectomy (NC). -To evaluate progression-free survival in patients undergoing CN after treatment with cabozantinib. -To evaluate overall survival in patients undergoing CN after a 12-week course of treatment with cabozantinib. -To evaluate the safety and tolerance of cabozantinib when administered before cytoreductive surgery, on the basis of the incidence and intensity of treatment-related adverse events reported during the study and classified according to the NCI CTCAE v4.03, and surgical complications according to the Clavien-Dindo classification system. -To evaluate changes in serum molecular markers of renal cell carcinoma associated with cabozantinib treatment in patients who are candidates for CN.;Primary end point(s): Objective response to preoperative treatment with cabozantinib, defined as the percentage of patients that reach a total or partial radiological response after a 12-week course of treatment with cabozantinib, defined according to the RECIST 1.1 criteria (Eisenhauer et al., 2009);Timepoint(s) of evaluation of this end point: After a 12-week course of treatment with cabozantinib (visit 2) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Better objective response during treatment with cabozantinib, defined as the percentage of patients that reach a total or partial radiological response during treatment with cabozantinib. 2. Progression Free Survival, defined as the time (in months) elapsed since the start of treatment with cabozantinib until the progression of the disease (according to the RECIST criteria 1.1) or the death of the patient. 3. Percentage of patients free of progression (according to the RECIST criteria1.1) after 12 months from the start of treatment with cabozantinib. 4. Overall Survival, defined as the time (in months) elapsed since the start of treatment with cabozantinib until the death of the patient. 5. Frequency of adverse events related to cabozantinib registered during the study. 6. Variation in the concentration of biomarkers from the beginning of treatment with cabozantinb until its completion.;Timepoint(s) of evaluation of this end point: 1. During all study 2. During all study 3. Final Visit (12 months from the start of treatment with cabozantinib) 4. During all study 5. During all study 6. Basal Visit, D1C1, D1C3, D1C4, Final Visit (12 months from the start of treatment with cabozantinib) | — |
Countries
Spain
Contacts
Public ContactPLATAFORMA DE ENSAYOS CLÍNICOS
Fundación ONCOSUR
Outcome results
None listed