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

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

Combined sunitinib and bevacizumab in advanced renal cell carcinoma.

Study Overview

• Status: Unknown
• Conditions: Renal Cell Carcinoma
• Intervention / Treatment: Drug: Sunitinib; Drug: Bevacizumab

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.

• Study Type: Interventional
• Enrollment (Anticipated): 77
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Saudi Arabia
  • Riyadh, Saudi Arabia, 11211
    • Recruiting
    • Oncology Centre, King Faisal Specialist Hospital and Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sunitinib and Bevacizumab Arm; Phase I/II Combined Alternating Sunitinib and Bevacizumab (Avastin®) in Advanced Renal Cell carcinoma (CASA)Combined Alternating Sunitinib and Bevacizumab	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; Other Names: Sutent; Drug: Bevacizumab; Monoclonal antibody against vascular endothelial growth factor: given intravenously on day 29 of each sunitinib cycle; Other Names: Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: King Faisal Specialist Hospital & Research Center
• Investigators: Principal Investigator: Shouki Bazarbashi, MD, King Faisal Specialist Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: March 24, 2015
• First Submitted That Met QC Criteria: September 27, 2016
• First Posted (Estimate): September 29, 2016

Study Record Updates

• Last Update Posted (Actual): August 10, 2018
• Last Update Submitted That Met QC Criteria: August 9, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib; Bevacizumab
• Other Study ID Numbers: 2141-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No- unless the data are so encouraging then this can be done

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No