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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00738530




Registration number
NCT00738530
Ethics application status
Date submitted
19/08/2008
Date registered
20/08/2008
Date last updated
23/06/2016

Titles & IDs
Public title
A Study of Avastin (Bevacizumab) Added to Interferon Alfa-2a (Roferon) Therapy in Patients With Metastatic Renal Cell Cancer With Nephrectomy
Scientific title
A Randomised, Double-blind Study to Evaluate the Efficacy and Safety of Avastin Plus Roferon Compared With Placebo Plus Roferon on Overall Survival and Tumor Assessment in Nephrectomised Patients With Metastatic Clear Cell Renal Cell Carcinoma
Secondary ID [1] 0 0
2004-000282-35
Secondary ID [2] 0 0
BO17705
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Cell Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bevacizumab [Avastin]
Treatment: Drugs - Interferon alfa 2a [Roferon]
Treatment: Drugs - Placebo

Experimental: Bevacizumab + IFN-Alfa-2A - Bevacizumab infusions will be administered every 2 weeks at a dose of 10 milligram per kilogram (mg/kg) for 52 weeks or until disease progression or unacceptable toxicity. Interferon alfa-2a (IFN-Alfa-2A) will be administered 3 times per week as a subcutaneous injection at a dose of 9 million international units (MIU) for 52 weeks or until disease progression or major toxicity.

Placebo Comparator: Placebo + IFN-Alfa-2A - Placebo matched with Bevacizumab infusions will be administered every 2 weeks for 52 weeks or until disease progression or unacceptable toxicity. IFN-Alfa-2A will be administered 3 times per week as a subcutaneous injection at a dose of 9 MIU for 52 weeks or until disease progression or major toxicity.


Treatment: Drugs: Bevacizumab [Avastin]
10 mg/kg IV every 2 weeks

Treatment: Drugs: Interferon alfa 2a [Roferon]
9 MIU SC 3 times/week

Treatment: Drugs: Placebo
IV every 2 weeks

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Who Died
Timepoint [1] 0 0
Baseline up to 4.25 years
Primary outcome [2] 0 0
Overall Survival (OS) Duration - Duration of survival was defined as the time between the date of randomization and date of death due to any cause. Participants still alive at the time of analysis were censored at the date they were last known to be alive. Kaplan-Meier estimates were used for analysis.
Timepoint [2] 0 0
Baseline until death (up to 4.25 years)
Secondary outcome [1] 0 0
Percentage of Participants With Disease Progression or Death - Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.
Timepoint [1] 0 0
Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
Secondary outcome [2] 0 0
Progression Free Survival (PFS) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) - Progression-free survival was defined as the time between the date of randomization and the first date of documented progression or date of death due to any cause, whichever occurred first. Tumor assessment was performed using modified RECIST. Progressive disease was defined as at least a 20 percentage(%) increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants without an event were censored at the date of last follow-up for progression or date of last available tumor measurement if no follow-up assessment for progression was performed. Participants who were randomized but not exposed to study drug and had no further follow-up were censored on the day of randomization.
Timepoint [2] 0 0
Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
Secondary outcome [3] 0 0
Time to Progression (TTP) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) - Time to progression was defined as the time between date of randomization and date of documented progression. Tumor assessment was performed using mRECIST. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants without an event (including participants who died before progressive disease) were censored at the date of last follow-up for progression or date of last available tumor measurement if no follow-up assessment for progression was performed. Participants who were randomized but not exposed to study drug and had no further follow-up were censored on the day of randomization.
Timepoint [3] 0 0
Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
Secondary outcome [4] 0 0
Percentage of Participants With Treatment Failure - Treatment failure is defined as insufficient therapeutic response (including disease progression), death, withdrawal of treatment due to adverse events or laboratory abnormality, or withdrawal of informed consent. Tumor assessment was performed using mRECIST. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.
Timepoint [4] 0 0
Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
Secondary outcome [5] 0 0
Time to Treatment Failure (TTF) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) - Time to treatment failure was defined as the time between the date of randomization and the date of insufficient therapeutic response (including disease progression), death, withdrawal of treatment due to adverse events or laboratory abnormality, or withdrawal of informed consent. Tumor assessment was performed using mRECIST. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants without an event were censored at the date of last tumor assessment or last treatment administration, whichever occurred last. Participants who were randomized but not exposed to study drug and had no further follow-up were censored on the day of randomization.
Timepoint [5] 0 0
Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
Secondary outcome [6] 0 0
Percentage of Participants With Objective Response According to mRECIST - Objective response referred to participants with complete response (CR) or partial response (PR). CR: disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR: greater than or equal to (>=) 30% decrease in sum of the longest diameter (LD) of all target lesions taking as reference the screening sum LD. To be assigned a status of PR or CR, changes in tumor measurements had to be confirmed by repeat assessments that should have been performed no less than 4 weeks after the criteria for response were first met. Longer intervals as determined by the study protocol were also appropriate.
Timepoint [6] 0 0
Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
Secondary outcome [7] 0 0
Percentage of Participants With Best Overall Response According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) - Best response recorded from the start of treatment until disease progression. Based on assessment of CR, PR, stable disease (SD), or progressive disease (PD), according to mRECIST. CR: disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR: >=30% decrease under baseline of the sum of the LD of all target lesions. CR and PR persist on repeat imaging study at least 4 weeks after initial documentation. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Reference is the smallest sum LD. PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.
Timepoint [7] 0 0
Baseline until disease progression or death, whichever occurred first (assessed at baseline, Weeks 8, 16, 24, 32, 44, 56, 68 thereafter every 12 weeks up to week 104 and then every 6 months up to 4.25 years)
Secondary outcome [8] 0 0
Change From Baseline in Karnofsky Performance Status - Karnofsky performance score is used to quantify participant's general well-being and activities of daily life and participants were classified based on their functional impairment. Karnofsky performance score is 11 level score which ranges between 0 (death) to 100 (no evidence of disease). Higher score means higher ability to perform daily tasks.
Timepoint [8] 0 0
Baseline, Week 7, 15, 23, 31, 43

Eligibility
Key inclusion criteria
- metastatic renal cell cancer (clear cell type);

- nephrectomy;

- absence of proteinuria.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- prior systemic treatment for metastatic renal cell cancer;

- major surgical procedure, open biopsy or significant traumatic injury within 28 days
prior to study treatment start;

- presence of brain metastases or spinal cord compression;

- ongoing need for full dose anticoagulants;

- uncontrolled hypertension;

- clinically significant cardiovascular disease.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Brisbane
Recruitment hospital [3] 0 0
- Canberra
Recruitment hospital [4] 0 0
- Frankston
Recruitment hospital [5] 0 0
- Kurralta Park
Recruitment hospital [6] 0 0
- Melbourne
Recruitment hospital [7] 0 0
- Perth
Recruitment hospital [8] 0 0
- Sydney
Recruitment postcode(s) [1] 0 0
5011 - Adelaide
Recruitment postcode(s) [2] 0 0
5041 - Adelaide
Recruitment postcode(s) [3] 0 0
4006 - Brisbane
Recruitment postcode(s) [4] 0 0
2606 - Canberra
Recruitment postcode(s) [5] 0 0
3199 - Frankston
Recruitment postcode(s) [6] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [7] 0 0
3128 - Melbourne
Recruitment postcode(s) [8] 0 0
6009 - Perth
Recruitment postcode(s) [9] 0 0
2031 - Sydney
Recruitment postcode(s) [10] 0 0
2139 - Sydney
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Antwerpen
Country [2] 0 0
Belgium
State/province [2] 0 0
Bruxelles
Country [3] 0 0
Belgium
State/province [3] 0 0
Wilrijk
Country [4] 0 0
Czech Republic
State/province [4] 0 0
Ceské Budejovice
Country [5] 0 0
Czech Republic
State/province [5] 0 0
Chomutov
Country [6] 0 0
Czech Republic
State/province [6] 0 0
Hradec Kralove
Country [7] 0 0
Czech Republic
State/province [7] 0 0
Plzen
Country [8] 0 0
Finland
State/province [8] 0 0
Tampere
Country [9] 0 0
Finland
State/province [9] 0 0
Turku
Country [10] 0 0
France
State/province [10] 0 0
Angers
Country [11] 0 0
France
State/province [11] 0 0
Bordeaux
Country [12] 0 0
France
State/province [12] 0 0
Caen
Country [13] 0 0
France
State/province [13] 0 0
Clermont Ferrand
Country [14] 0 0
France
State/province [14] 0 0
Grenoble
Country [15] 0 0
France
State/province [15] 0 0
Lille
Country [16] 0 0
France
State/province [16] 0 0
Limoges
Country [17] 0 0
France
State/province [17] 0 0
Lyon
Country [18] 0 0
France
State/province [18] 0 0
Marseille
Country [19] 0 0
France
State/province [19] 0 0
Nice
Country [20] 0 0
France
State/province [20] 0 0
Poitiers
Country [21] 0 0
France
State/province [21] 0 0
Saint Herblain
Country [22] 0 0
France
State/province [22] 0 0
Strasbourg
Country [23] 0 0
France
State/province [23] 0 0
Suresnes
Country [24] 0 0
France
State/province [24] 0 0
Toulouse
Country [25] 0 0
France
State/province [25] 0 0
Villejuif
Country [26] 0 0
Germany
State/province [26] 0 0
Berlin
Country [27] 0 0
Germany
State/province [27] 0 0
Darmstadt
Country [28] 0 0
Germany
State/province [28] 0 0
Hamburg
Country [29] 0 0
Germany
State/province [29] 0 0
Hannover
Country [30] 0 0
Germany
State/province [30] 0 0
Mannheim
Country [31] 0 0
Germany
State/province [31] 0 0
Marburg
Country [32] 0 0
Germany
State/province [32] 0 0
München
Country [33] 0 0
Germany
State/province [33] 0 0
Planegg
Country [34] 0 0
Hungary
State/province [34] 0 0
Budapest
Country [35] 0 0
Hungary
State/province [35] 0 0
Szombathely
Country [36] 0 0
Israel
State/province [36] 0 0
Holon
Country [37] 0 0
Israel
State/province [37] 0 0
Ramat-gan
Country [38] 0 0
Israel
State/province [38] 0 0
Rehovot
Country [39] 0 0
Israel
State/province [39] 0 0
Tel Aviv
Country [40] 0 0
Israel
State/province [40] 0 0
Zerifin
Country [41] 0 0
Italy
State/province [41] 0 0
Livorno
Country [42] 0 0
Italy
State/province [42] 0 0
Milano
Country [43] 0 0
Italy
State/province [43] 0 0
Modena
Country [44] 0 0
Italy
State/province [44] 0 0
Napoli
Country [45] 0 0
Italy
State/province [45] 0 0
Perugia
Country [46] 0 0
Italy
State/province [46] 0 0
Roma
Country [47] 0 0
Italy
State/province [47] 0 0
Rozzano
Country [48] 0 0
Italy
State/province [48] 0 0
Torino
Country [49] 0 0
Netherlands
State/province [49] 0 0
Amsterdam
Country [50] 0 0
Netherlands
State/province [50] 0 0
Nijmegen
Country [51] 0 0
Norway
State/province [51] 0 0
Oslo
Country [52] 0 0
Norway
State/province [52] 0 0
Stavanger
Country [53] 0 0
Norway
State/province [53] 0 0
Trondheim
Country [54] 0 0
Norway
State/province [54] 0 0
Ålesund
Country [55] 0 0
Poland
State/province [55] 0 0
Bydgoszcz
Country [56] 0 0
Poland
State/province [56] 0 0
Krakow
Country [57] 0 0
Poland
State/province [57] 0 0
Lodz
Country [58] 0 0
Poland
State/province [58] 0 0
Olsztyn
Country [59] 0 0
Poland
State/province [59] 0 0
Tarnow
Country [60] 0 0
Poland
State/province [60] 0 0
Warszawa
Country [61] 0 0
Russian Federation
State/province [61] 0 0
Moscow
Country [62] 0 0
Russian Federation
State/province [62] 0 0
Obninsk
Country [63] 0 0
Russian Federation
State/province [63] 0 0
St Petersburg
Country [64] 0 0
Singapore
State/province [64] 0 0
Singapore
Country [65] 0 0
Spain
State/province [65] 0 0
Barcelona
Country [66] 0 0
Spain
State/province [66] 0 0
Granada
Country [67] 0 0
Spain
State/province [67] 0 0
Madrid
Country [68] 0 0
Spain
State/province [68] 0 0
Málaga
Country [69] 0 0
Spain
State/province [69] 0 0
Pontevedra
Country [70] 0 0
Spain
State/province [70] 0 0
Santander
Country [71] 0 0
Spain
State/province [71] 0 0
Valencia
Country [72] 0 0
Spain
State/province [72] 0 0
Zaragoza
Country [73] 0 0
Switzerland
State/province [73] 0 0
Basel
Country [74] 0 0
Switzerland
State/province [74] 0 0
Bern
Country [75] 0 0
Switzerland
State/province [75] 0 0
Geneve
Country [76] 0 0
Taiwan
State/province [76] 0 0
Chang Gung
Country [77] 0 0
Taiwan
State/province [77] 0 0
Kaohsiung
Country [78] 0 0
Taiwan
State/province [78] 0 0
Taichung
Country [79] 0 0
Taiwan
State/province [79] 0 0
Taipei
Country [80] 0 0
United Kingdom
State/province [80] 0 0
London
Country [81] 0 0
United Kingdom
State/province [81] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This 2-arm study will evaluate the efficacy and safety of Avastin versus placebo in
combination with Roferon as first-line treatment in participants with metastatic renal cell
cancer (clear cell type) who have had nephrectomy. The anticipated time of study treatment is
1-2 years, and the target sample size is greater than (>)500 individuals.
Trial website
https://clinicaltrials.gov/show/NCT00738530
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications