Combined Alternating Sunitinib and Bevacizumab (Avastin®) in Advanced Renal Cell Carcinoma (CASA)

Renal Cell Carcinoma Clinical Trial

Official title:

Phase I/II Combined Alternating Sunitinib and Bevacizumab (Avastin®) in Advanced Renal Cell Carcinoma (CASA)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02919371
• Other study ID #: 2141-102
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 2014
• Est. completion date: December 2021

Study information

• Verified date: August 2018
• Source: King Faisal Specialist Hospital & Research Center
• Contact: Shouki Bazarbashi, MD
• Phone: 00966 11 442 3935
• Email: bazarbashi[@]kfshrc.edu.sa
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Combined sunitinib and bevacizumab in advanced renal cell carcinoma.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 77
• Est. completion date: December 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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)

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

Drug:
• Sunitinib
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
• Bevacizumab
Monoclonal antibody against vascular endothelial growth factor: given intravenously on day 29 of each sunitinib cycle

Locations

Country	Name	City	State
Saudi Arabia	Oncology Centre, King Faisal Specialist Hospital and Research Centre	Riyadh

Sponsors (1)

Lead Sponsor	Collaborator
King Faisal Specialist Hospital & Research Center

Country where clinical trial is conducted

Saudi Arabia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bevacizumab maximum tolerated dose, in combination with sunitinib	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	12 weeks from enrolling patient # 6
Primary	Assess response rate to the combination of sunitinib and bevacizumab	response rate is the combination of partial response and complete response	Through study completion, an average of 6 months
Primary	Assess the progression free survival on the combination of sunitinib and bevacizumab	Progression free survival will be calculated from time of starting therapy till progression or death whichever comes first	up to 5 years
Secondary	Overall survival of patients in this regimen	Overall survival will be calculated from date of start on therapy till death	Participants will be followed for the duration of hospital stay, up to 5 years
Secondary	Number of participants with treatment related-adverse effects as assessed by CTCAE v 4.03	toxicity will be graded according to the NCI-CTC version 4.03	up to 5 years