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

Primary Purpose

Renal Cell Cancer

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
bevacizumab [Avastin]
interferon alfa-2a
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Renal Cell Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.

Full Information

First Posted
November 21, 2008
Last Updated
May 22, 2015
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT00796757
Brief Title
A Study of Avastin (Bevacizumab) in Combination With Low-Dose-Interferon in Patients With Metastatic Clear Cell Renal Cell Carcinoma (RCC).
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2015
Overall Recruitment Status
Completed
Study Start Date
December 2008 (undefined)
Primary Completion Date
February 2012 (Actual)
Study Completion Date
February 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Cell Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
146 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
bevacizumab [Avastin]
Intervention Description
10mg/kg iv infusion every 2 weeks
Intervention Type
Drug
Intervention Name(s)
interferon alfa-2a
Intervention Description
3 MIU sc t.i.w.
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS) - Percentage of Participants Estimated to be Progression Free at 12 and 24 Months
Description
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.
Time Frame
12 and 24 months
Title
PFS - Percentage of Participants With an Event
Description
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.
Time Frame
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
Title
PFS - Time to Event
Description
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.
Time Frame
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 Measure Information:
Title
Percentage of Participants With a Best Overall Response of Complete Reponse (CR) or Partial Response (PR)
Description
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.
Time Frame
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
Title
Overall Survival (OS) - Percentage of Participants Estimated to be Alive at 12 and 24 Months
Description
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.
Time Frame
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
Title
OS - Percentage of Participants With an Event
Description
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.
Time Frame
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
Title
OS - Time to Event
Description
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.
Time Frame
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
Title
Percentage of Participants With Any Health Problems as Assessed by the European Quality of Life 5 Dimensions (EQ-5D) by Visit
Description
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.
Time Frame
Screening/Baseline, Cycle 7, Cycle 25, Cycle 43, Cycle 61, and End of Treatment (EOT)
Title
EQ-5D - Visual Analog Scale (VAS)
Description
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.
Time Frame
Screening/Baseline, Cycle 7, Cycle 25, Cycle 43, Cycle 61, and EOT

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Olomouc
ZIP/Postal Code
775 20
Country
Czech Republic
City
Praha 2
ZIP/Postal Code
128 08
Country
Czech Republic
City
Tallinn
ZIP/Postal Code
10617
Country
Estonia
City
Tallinn
ZIP/Postal Code
13419
Country
Estonia
City
Tartu
ZIP/Postal Code
50406
Country
Estonia
City
Seinäjoki
ZIP/Postal Code
60220
Country
Finland
City
Turku
ZIP/Postal Code
20520
Country
Finland
City
Arnsberg
ZIP/Postal Code
59755
Country
Germany
City
Augsburg
ZIP/Postal Code
86156
Country
Germany
City
Berlin
ZIP/Postal Code
10117
Country
Germany
City
Berlin
ZIP/Postal Code
13055
Country
Germany
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
City
Homburg/Saar
ZIP/Postal Code
66424
Country
Germany
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
City
München
ZIP/Postal Code
81241
Country
Germany
City
Münster
ZIP/Postal Code
48149
Country
Germany
City
Offenburg
ZIP/Postal Code
77652
Country
Germany
City
Planegg
ZIP/Postal Code
82152
Country
Germany
City
Stuttgart
ZIP/Postal Code
70174
Country
Germany
City
Weiden
ZIP/Postal Code
92637
Country
Germany
City
Larissa
ZIP/Postal Code
41 110
Country
Greece
City
Thessaloniki
ZIP/Postal Code
54639
Country
Greece
City
Thessaloniki
ZIP/Postal Code
56429
Country
Greece
City
Milano
ZIP/Postal Code
20100
Country
Italy
City
Napoli
ZIP/Postal Code
80131
Country
Italy
City
Pisa
ZIP/Postal Code
56100
Country
Italy
City
Kaunas
ZIP/Postal Code
50009
Country
Lithuania
City
Vilnius
ZIP/Postal Code
08661
Country
Lithuania
City
Amstelveen
ZIP/Postal Code
1186 AH
Country
Netherlands
City
Eindhoven
ZIP/Postal Code
5623 EJ
Country
Netherlands
City
Maastricht
ZIP/Postal Code
6229 HX
Country
Netherlands
City
Nijmegen
ZIP/Postal Code
6525 GA
Country
Netherlands
City
Barnaul
ZIP/Postal Code
656049
Country
Russian Federation
City
Ekaterinburg
ZIP/Postal Code
620102
Country
Russian Federation
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
City
Moscow
ZIP/Postal Code
117837
Country
Russian Federation
City
Moscow
ZIP/Postal Code
125284
Country
Russian Federation
City
Obninsk
ZIP/Postal Code
249020
Country
Russian Federation
City
St Petersburg
Country
Russian Federation
City
UFA
ZIP/Postal Code
450054
Country
Russian Federation
City
Ulyanovsk
ZIP/Postal Code
432063
Country
Russian Federation
City
Eskilstuna
ZIP/Postal Code
63188
Country
Sweden
City
Linkoeping
ZIP/Postal Code
58185
Country
Sweden
City
Sundsvall
ZIP/Postal Code
85186
Country
Sweden
City
Vaxjo
ZIP/Postal Code
35185
Country
Sweden
City
Aarau
ZIP/Postal Code
5000
Country
Switzerland
City
Locarno
ZIP/Postal Code
6601
Country
Switzerland
City
Zürich
ZIP/Postal Code
8063
Country
Switzerland
City
Cambridge
ZIP/Postal Code
CB2 2QQ
Country
United Kingdom
City
Cardiff
ZIP/Postal Code
CF14 2TL
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
23803225
Citation
Melichar B, Bracarda S, Matveev V, Alekseev B, Ivanov S, Zyryanov A, Janciauskiene R, Fernebro E, Mulders P, Osborne S, Jethwa S, Mickisch G, Gore M, van Moorselaar RJ, Staehler M, Magne N, Bellmunt J; BEVLiN Investigators. A multinational phase II trial of bevacizumab with low-dose interferon-alpha2a as first-line treatment of metastatic renal cell carcinoma: BEVLiN. Ann Oncol. 2013 Sep;24(9):2396-402. doi: 10.1093/annonc/mdt228. Epub 2013 Jun 26.
Results Reference
derived

Learn more about this trial

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

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