Renal Cell Carcinoma
Conditions
Brief summary
Combined sunitinib and bevacizumab in advanced renal cell carcinoma.
Detailed description
This is a phase I/II trial of combined sunitinib and bevacizumab in advanced renal cell carcinoma ( CASBA) where Bevacizumab will be used only on day 29 of each 6 weeks sunitinib cycle.
Interventions
DRUGSunitinib
Oral therapy ( Anti-vascular endothelial growth factor Tyrosin Kinase Inhibitor): given as 50 mg daily from day 1 to day 28- cycle repeated every 42 days
DRUGBevacizumab
Monoclonal antibody against vascular endothelial growth factor: given intravenously on day 29 of each sunitinib cycle
Sponsors
King Faisal Specialist Hospital & Research Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed renal cell carcinoma with clear cell histology ( mixed histology with clear cell component is accepted) 2. Patient should have either locally advanced or metastatic disease 3. No prior anti-cancer therapy 4. Age ≥ 18 years 5. Life expectancy of 3 months or more 6. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 7. Performance status 0-2 by ECOG scale 8. Patients with controlled brain metastasis are accepted 9. Adequate renal function: serum creatinine ≤ 2 times the institutional upper limit of normal 10. Adequate hepatic function: total bilirubin within normal institutional limits, serum AST and ALT levels ≤2 times the institutional upper limit of normal or ≤ 5 times the institutional upper limit of normal of elevated because of liver involvement 11. Coagulation (PT ≤ 1.5 times the institutional upper limit of normal) 12. Adequate hematological values: leukocyte count ≥3.0 x 109/L, an absolute neutrophil count ≥1.5 x 109/L, a platelet count ≥100 x 109/L and hemoglobin ≥ 9.0 g/dL 13. Urine dipstick for proteinuria \<1+, patients discovered to have ≥ 1+ on dipstick urinanalysis at baseline should have urine protein/urine creatinine ratio ≤1 14. Singed written informed consent before enrolment 15. Patient should have unresectable disease ( for both the primary tumor and the metastasis)
Exclusion criteria
1. Inability to comply with the protocol therapy 2. Uncontrolled hypertension defined as BP more than 160 systolic and or more than 100 diastolic despite adequate treatment at the time of treatment initiation. 3. Severe cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, myocardial infarction, significant arrhythmias or Transient ischemic attack (TIA) or cerebrovascular accident (CVA) in the last 6 months 4. Major bleeding disorder, significant traumatic injury or recent major surgery within 28 days of starting therapy. Or minor surgery (FNA/Core biopsy) within 7 days of starting therapy 5. History of abdominal abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months 6. Pre-existing thyroid abnormality 7. Concurrent proarrhythmic medications including terfenadine, quinidine, procainamide, disopyramide, sotalol, bepridil, haloperidol, risperidone, indapamide and flecainide 8. Recent significant hemoptysis (1/2 tea spoon red blood within last month) 9. Concurrent medication that either CYP 450 3A4 inducers or inhibitors 10. Concurrent use of proarrhythmic medications including terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide and flecainide 11. Pregnancy or breast feeding, or patient refusal to use appropriate contraception for female patients in childbirth age 12. Previous malignancy within 5 years, except adequately treated non melanomatous skin cancer or in situ cervical cancer 13. Psychiatric or mental disorder, precluding understanding of the information of the trial related topics and giving valid informed consent 14. Any psychological, familial, geographic or social circumstances which could impair the patient ability to participate in the trial and comply with follow up. 15. Any circumstance which might impair the patient's ability to comply with an out-patient regimen 16. Active uncontrolled infection 17. Serious underlying medical condition (in the judgment of the investigator) which could impair the ability of the patient to participate in the trial 18. Treatment with other experimental drugs within 30 days of entry into the trial 19. Treatment with other anti-cancer therapy 20. Legal incapacity 21. Significant proteinuria (urine protein: creatinine ratio \> 1.0)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bevacizumab maximum tolerated dose, in combination with sunitinib | 12 weeks from enrolling patient # 6 | This is the phase I part of the study. patient will enroll on Bevacizumab dose of 5 mg/kg body weight. If no dose limiting toxicity in 1st 6 patients, the dose will be escalated to 10 mg/kg in the remainder of the patients |
| Assess response rate to the combination of sunitinib and bevacizumab | Through study completion, an average of 6 months | response rate is the combination of partial response and complete response |
| Assess the progression free survival on the combination of sunitinib and bevacizumab | up to 5 years | Progression free survival will be calculated from time of starting therapy till progression or death whichever comes first |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival of patients in this regimen | Participants will be followed for the duration of hospital stay, up to 5 years | Overall survival will be calculated from date of start on therapy till death |
| Number of participants with treatment related-adverse effects as assessed by CTCAE v 4.03 | up to 5 years | toxicity will be graded according to the NCI-CTC version 4.03 |
Countries
Saudi Arabia
Contacts
Primary ContactShouki Bazarbashi, MD
Backup ContactFazal Hussain, MD
Outcome results
None listed