Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Avastin (Bevacizumab) Added to Interferon Alfa-2a (Roferon) Therapy in Patients With Metastatic Renal Cell Cancer With Nephrectomy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00738530
Recruitment Status : Completed
First Posted : August 20, 2008
Results First Posted : June 23, 2016
Last Update Posted : June 23, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE August 19, 2008
First Posted Date  ICMJE August 20, 2008
Results First Submitted Date  ICMJE March 22, 2016
Results First Posted Date  ICMJE June 23, 2016
Last Update Posted Date June 23, 2016
Study Start Date  ICMJE June 2004
Actual Primary Completion Date September 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 16, 2016)
  • Percentage of Participants Who Died [ Time Frame: Baseline up to 4.25 years ]
  • Overall Survival (OS) Duration [ Time Frame: Baseline until death (up to 4.25 years) ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 19, 2008)
Overall survival. [ Time Frame: Week 52 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2016)
  • Percentage of Participants With Disease Progression or Death [ Time Frame: 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) ]
    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.
  • Progression Free Survival (PFS) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) [ Time Frame: 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) ]
    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.
  • Time to Progression (TTP) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) [ Time Frame: 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) ]
    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.
  • Percentage of Participants With Treatment Failure [ Time Frame: 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) ]
    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.
  • Time to Treatment Failure (TTF) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) [ Time Frame: 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) ]
    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.
  • Percentage of Participants With Objective Response According to mRECIST [ Time Frame: 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) ]
    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.
  • Percentage of Participants With Best Overall Response According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) [ Time Frame: 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) ]
    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.
  • Change From Baseline in Karnofsky Performance Status [ Time Frame: Baseline, Week 7, 15, 23, 31, 43 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 19, 2008)
Efficacy: Progression-free survival, time to disease progression, time to treatment failure, objective response rates. Safety: Hematology, serum chemistry, urinalysis, and adverse events. [ Time Frame: Throughout study ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Avastin (Bevacizumab) Added to Interferon Alfa-2a (Roferon) Therapy in Patients With Metastatic Renal Cell Cancer With Nephrectomy
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Renal Cell Cancer
Intervention  ICMJE
  • Drug: Bevacizumab [Avastin]
    10 mg/kg IV every 2 weeks
  • Drug: Interferon alfa 2a [Roferon]
    9 MIU SC 3 times/week
  • Drug: Placebo
    IV every 2 weeks
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Bevacizumab [Avastin]
    • Drug: Interferon alfa 2a [Roferon]
  • 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.
    Interventions:
    • Drug: Interferon alfa 2a [Roferon]
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 16, 2009)
649
Original Estimated Enrollment  ICMJE
 (submitted: August 19, 2008)
638
Actual Study Completion Date  ICMJE September 2008
Actual Primary Completion Date September 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • metastatic renal cell cancer (clear cell type);
  • nephrectomy;
  • absence of proteinuria.

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Czech Republic,   Finland,   France,   Germany,   Hungary,   Israel,   Italy,   Netherlands,   Norway,   Poland,   Russian Federation,   Singapore,   Spain,   Switzerland,   Taiwan,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00738530
Other Study ID Numbers  ICMJE BO17705
2004-000282-35 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP