A Study of Avastin (Bevacizumab) in Combination With Low-Dose-Interferon in Patients With Metastatic Clear Cell Renal Cell Carcinoma (RCC).

Study Overview
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Brief Summary
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This single arm study will assess progression free survival, tumor response and safety of Avastin in combination with interferon alfa-2a (IFN) as first line treatment in patients with metastatic clear cell renal cell carcinoma. Patients will receive Avastin (10mg/kg iv) every 2 weeks in combination with a low dose of interferon alfa-2a (3 MIU sc three times per week (t.i.w.). The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.

Official Title
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An Open Label Study of the Effect of First Line Treatment With Avastin (Bevacizumab) in Combination With Low-dose Interferon on Progression-free Survival in Patients With Metastatic Clear Cell Renal Cell Carcinoma.

Conditions
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Renal Cell Cancer

Intervention / Treatment
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* Drug: bevacizumab [Avastin]
* Drug: interferon alfa-2a


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >=18 years of age; metastatic RCC with majority (>50%) of conventional clear-cell type; prior total nephrectomy for primary RCC; at least one measurable or non-measurable lesions; ECOG performance score of 0 or 2. Exclusion Criteria: prior systemic treatment for metastatic RCC; current or previously treated but non-stable CNS metastases or spinal cord compression; major surgery (including open biopsy) or radiation therapy within 28 days prior to enrollment; significant cardiovascular disease within 6 months prior to enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: bevacizumab [Avastin]<br>* 10mg/kg iv infusion every 2 weeks<br>Drug: interferon alfa-2a<br>* 3 MIU sc t.i.w.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) - Percentage of Participants Estimated to be Progression Free at 12 and 24 Months | PFS at 12 and 24 months is an estimate of the percentages of participants expected to be progression free at 12 and 24 months based on Kaplan-Meier survival analysis of the PFS data. PFS was defined as the time period from the first postbaseline tumor assessment to evidence of disease progression or death from any cause, whichever occurred first. Disease progression included evaluation solely due to symptomatic deterioration or death due to any reason. Censoring at start of any subsequent antineoplastic therapy was not performed. | 12 and 24 months | 
| PFS - Percentage of Participants With an Event | PFS was defined as the time period from the first postbaseline assessment tumor assessment to evidence of disease progression or death from any cause, whichever occurred first. Disease progression included evaluation solely due to symptomatic deterioration or death due to any reason. Censoring at start of any subsequent antineoplastic therapy was not performed. | Baseline, every 8 weeks to Week 32 then every 12 weeks to disease progression or a maximum of 2 years from enrollment of last participant | 
| PFS - Time to Event | PFS was defined as the time period from the first postbaseline assessment tumor assessment to evidence of disease progression or death from any cause, whichever occurred first. Disease progression included evaluation solely due to symptomatic deterioration or death due to any reason. Censoring at start of any subsequent antineoplastic therapy was not performed. | Baseline, every 8 weeks to Week 32 then every 12 weeks to disease progression or a maximum of 2 years from enrollment of last participant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Best Overall Response of Complete Reponse (CR) or Partial Response (PR) | Percentage of participants with objective response, termed responders, based assessment of confirmed CR or confirmed PR according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses were those that persisted on repeat imaging study greater than or equal to (≥)4 weeks after initial documentation of response. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis less than [<]10 millimeters [mm]). No new lesions. PR was defined as ≥30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. | Baseline, every 8 weeks to Week 32 then every 12 weeks to disease progression or a maximum of 2 years from enrollment of last participant | 
| Overall Survival (OS) - Percentage of Participants Estimated to be Alive at 12 and 24 Months | OS at 12 and 24 months is the estimate of the percentages of participants expected to alive at 12 and 24 months based on Kaplan-Meier survival analysis of the survival data. Median OS was defined as the time period from the first bevacizumab infusion to death from any cause. Censoring at start of any subsequent antineoplastic therapy was not performed. | Day 0, every 2 weeks until disease progression or end of treatment visit (28 days after last bevacizumab infusion, every 3 months during follow-up, or a maximum of 2 years from enrollment of last participant | 
| OS - Percentage of Participants With an Event | OS was defined as the time period from the first bevacizumab infusion to death from any cause. Censoring at start of any subsequent antineoplastic therapy was not performed. | Day 0, every 2 weeks until disease progression or end of treatment visit (28 days after last bevacizumab infusion, every 3 months during follow-up, or a maximum of 2 years from enrollment of last participant | 
| OS - Time to Event | OS was defined as the time period from the first bevacizumab infusion to death from any cause. Censoring at start of any subsequent antineoplastic therapy was not performed. | Day 0, every 2 weeks until disease progression or end of treatment visit (28 days after last bevacizumab infusion, every 3 months during follow-up, or a maximum of 2 years from enrollment of last participant | 
| Percentage of Participants With Any Health Problems as Assessed by the European Quality of Life 5 Dimensions (EQ-5D) by Visit | EQ-5D is a standardized, participant-administered measure of health outcome. It provides a descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), using 3 levels (no, moderate, or extreme problems) and a single index value characterizing current health status using a 100-point visual analog scale (0=worst, 100=best). Answers from the questionnaire for each dimension (mobility, self-care, usual activity, pain/discomfort, and anxiety/depression) was classified into one of 2 categories: 'no problems' or 'any problems', and the percentage of participants in each category was determined. | Screening/Baseline, Cycle 7, Cycle 25, Cycle 43, Cycle 61, and End of Treatment (EOT) | 
| EQ-5D - Visual Analog Scale (VAS) | EQ-5D: participant-rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 millimeters (mm) (best imaginable health state); higher scores indicate a better health state. Participants were asked to rate their health state and mark the line; the distance from the left edge was recorded. For change from baseline a negative value represents a worsening in the health state and a positive value represents an improvement in the health state. | Screening/Baseline, Cycle 7, Cycle 25, Cycle 43, Cycle 61, and EOT |