Clinical Trial: Safety and Efficacy of Bevacizumab Plus RAD001 Versus Interferon Alfa-2a and Bevacizumab for the First-line Treatment in Adult Patients With Kidney Cancer
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: A Randomized, Open-label, Multi-center Phase II Study to Compare Bevacizumab Plus RAD001 Versus Interferon Alfa-2a Plus Bevacizumab for the First-line Treatment of Patients With Metastatic
Brief Summary: To estimate the difference in efficacy and safety of bevacizumab and RAD001 compared to bevacizumab and interferon alfa-2a for first-line treatment of patients with metastatic carcinoma of the kidney.
Detailed Summary:
Sponsor: Novartis Pharmaceuticals
Current Primary Outcome: Progression-free Survival (PFS) of Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab [ Time Frame: Time from randomization to the date of radiological progressive disease as per independent central review, death from any cause, or last tumor assessment, reported between date of first participant randomized until 31Dec2011, cutoff date. ]
Original Primary Outcome: CT/MRI scans
Current Secondary Outcome:
- Overall Survival (OS) Treatment Effect in Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab [ Time Frame: Time from randomization to the date of death from any cause, reported between date of first participant randomized and up to 2 years after the last participant randomized (data cutoff: 30Aug2012) ]Overall survival (OS) was defined as the time of randomization to the date of death due to any cause.
- Best Overall Response in Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab [ Time Frame: Time from first participant randomized until 31Dec2011, cutoff date. ]Overall response is defined as the number of participants having achieved confirmed Complete Response (CR) + Partial Response (PR). Confirmed CR = at least two determinations of CR at least 4 weeks apart before progression. Confirmed PR = at least two determinations of PR or better at least 4 weeks apart before progression. CR required a disappearance of all target and non-target lesions. PR required at least a 30% decrease in the sum of the longest diameters of all target lesions, taking as a reference the baseline sum of the longest diameters. Disease progression was defined as: 1) a 20% increase in the sum of the longest diameter of all target lesions, taking as reference the smallest sum of the longest diameters of all target lesions recorded at or after baseline or 2) the appearance of a new lesions or 3) the unequivocal progression of non-target lesions overall.
- Response Duration Differences in Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab [ Time Frame: Time from first documented response date of radiological progressive disease as per independent central review, death due to underlying cancer, or last tumor assessment, reported between date of first participant randomized until 31Dec2011, cut-off date. ]The duration of response, applied only to participants with best overall response at CR or PR, is defined as the number of days between the date of first documented response (CR or PR) and the date of the event: radiological progression as per central review or death due to underlying cancer, whichever occurs first. If no event, participant is censored at the last adequate assessment.
- Number of Participants Who Experienced Adverse Events (AEs), Serious Adverse Events and Deaths [ Time Frame: From the first participant randomized until the last patient discontinued the study treatment + 28 days ]Participants were monitored for adverse events, serious adverse events and deaths throughout the study. Participants were assessed continuously at each 28-day cycle.
- Time to Definitive Deterioration of the Functional Assessment of Cancer Therapy Kidney Symptom Index, Disease Related Symptoms (FKSI-DRS) Risk Score by at Least 2 Score Units [ Time Frame: Time from randomization to the date of definitive deterioration (defined as no later increase above the threshold observed during the study), or date of last assessment, reported between date of first patient randomized until 31Dec2011 ]The analysis of this outcome measure was based on the FKSI-DRS scale which is a validated disease-related symptom index containing 9 items that measure symptoms predominantly related to kidney cancer. Each item is scored on a 5-point scale (0 = not at all; 4 = very much). If at least 5 of the 9 questions have been answered, the FKSI-DRS total score is calculated by subtracting nine times the mean of the scores of the answered items from 36. Participants with less than 5 out of the 9 questions answered will have a missing FKSI-DRS total score. The FKSI-DRS total score ranges from 0 (most severe symptoms) to 36 (no symptoms). Definitive deterioration is defined as a decrease by at least 2 units compared to baseline, with no later increase above this threshold observed during the study. A single measure reporting a decrease of at least 2 units was considered definitive only if it is the last one available for the participant.
- Time to Definitive Deterioration of the Global Health Status and the Physical Functioning (PF) Subscale Scores of the European Organization for the Research and Treatment of Cancer (EORTC)-Core Quality of Life Questionnaire (QLQ-C30) by at Least 10% [ Time Frame: Time from randomization to the date of definitive deterioration (defined as no later increase above the threshold observed during the study), or date of last assessment, reported between date of first participant randomized until 31Dec2011 ]The EORTC QLQ-C30 contains 30 items. These include five functional scales (physical, role, emotional, social and cognitive functioning), three symptom scales (fatigue, pain, nausea, and vomiting), a global health status/QoL scale, and six single items (dyspnea, diarrhea, constipation, anorexia, insomnia and financial impact). The PF subscale consists of 5 questions each scored from 1 (not at all) to 4 (very much). The score for the PF subscale and global health status range from 0 to 100, with a higher score representing a high level of functioning/high quality of life. Definitive deterioration by at least 10% is defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observ
Original Secondary Outcome: PRO
Information By: Novartis
Dates:
Date Received: July 15, 2008
Date Started: November 12, 2008
Date Completion:
Last Updated: February 13, 2017
Last Verified: February 2017
