Safety and Efficacy of Bevacizumab Plus RAD001 Versus Interferon Alfa-2a and Bevacizumab for the First-line Treatment in Adult Patients With Kidney Cancer

• ClinicalTrials.gov Identifier: NCT00719264
• Recruitment Status: Completed
• First Posted: July 21, 2008
• Results First Posted: May 7, 2014
• Last Update Posted: March 20, 2017
• Sponsor: Novartis Pharmaceuticals
• Collaborator: Roche Pharma AG
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Carcinoma; Adenocarcinoma; Renal Cell; Nephroid Carcinoma; Hypernephroid
• Interventions: Drug: RAD001(everolimus); Drug: interferon alfa-2a; Drug: bevacizumab
• Enrollment: 365

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Bevacizumab, RAD001 (Everolimus)	Bevacizumab, Interferon Alfa-2a (IFN)
Arm/Group Description	Participants received oral everolimus 10 mg qd plus intravenous bevacizumab 10mg/kg every 2 weeks.	Participants received subcutaneous IFN dose escalated from 3 MIU (million international unit) during week 1, 6 MIU during week 2, and 9 MIU during week 3 of treatment and subsequently (if tolerated), 3 times per week plus intravenous bevacizumab 10 mg/kg every 2 weeks.
Period Title: Overall Study
Started	182	183
Full Analysis Set	182	183
Safety Set	180	181
Completed	0	0
Not Completed	182	183
Reason Not Completed
Adverse Event	41	49
Death	13	10
Administrative Problems	6	4
Lost to Follow-up	1	1
Withdrawal by Subject	12	7
Protocol Deviation	1	3
New Cancer Therapy	4	2
Disease Progression	104	107

Baseline Characteristics

Arm/Group Title		Bevacizumab, RAD001 (Everolimus)	Bevacizumab, Interferon Alfa-2a (IFN)	Total
Arm/Group Description		Participants received oral everolimus 10 mg qd plus intravenous bevacizumab 10mg/kg every 2 weeks.	Participants received subcutaneous IFN dose escalated from 3 MIU (million international unit) during week 1, 6 MIU during week 2, and 9 MIU during week 3 of treatment and subsequently (if tolerated), 3 times per week plus intravenous bevacizumab 10 mg/kg every 2 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		182	183	365
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	182 participants	183 participants	365 participants
		60.71 (10.584)	59.93 (10.272)	60.32 (10.422)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	182 participants	183 participants	365 participants
	Female	44 24.2%	52 28.4%	96 26.3%
	Male	138 75.8%	131 71.6%	269 73.7%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS) of Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab
Description	Tumor response and disease progression were assessed using response evaluation criteria in solid tumors (RECIST), version 1.0. All target and non-target lesions identified at baseline were assessed using the same method, CT scan with contrast or MRI with contrast, throughout the trial. All scans were reviewed by independent, central radiology. 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.
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.

Outcome Measure Data

Analysis Population Description

Full Analysis Set: This set consists of all randomized participants.

Arm/Group Title	Bevacizumab, RAD001 (Everolimus)	Bevacizumab, Interferon Alfa-2a (IFN)
Arm/Group Description:	Participants received oral everolimus 10 mg qd plus intravenous bevacizumab 10mg/kg every 2 weeks.	Participants received subcutaneous IFN dose escalated from 3 MIU (million international unit) during week 1, 6 MIU during week 2, and 9 MIU during week 3 of treatment and subsequently (if tolerated), 3 times per week plus intravenous bevacizumab 10 mg/kg every 2 weeks.
Overall Number of Participants Analyzed	182	183
Median (95% Confidence Interval); Unit of Measure: Months
	9.3; (8.1 to 11.2)	10.0; (8.3 to 12.9)

2. Secondary Outcome

Title	Overall Survival (OS) Treatment Effect in Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab
Description	Overall survival (OS) was defined as the time of randomization to the date of death due to any cause.
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)

Outcome Measure Data

Analysis Population Description

Full Analysis Set: This set consists of all randomized participants.

Arm/Group Title	Bevacizumab, RAD001 (Everolimus)	Bevacizumab, Interferon Alfa-2a (IFN)
Arm/Group Description:	Participants received oral everolimus 10 mg qd plus intravenous bevacizumab 10mg/kg every 2 weeks.	Participants received subcutaneous IFN dose escalated from 3 MIU (million international unit) during week 1, 6 MIU during week 2, and 9 MIU during week 3 of treatment and subsequently (if tolerated), 3 times per week plus intravenous bevacizumab 10 mg/kg every 2 weeks.
Overall Number of Participants Analyzed	182	183
Median (95% Confidence Interval); Unit of Measure: Months
	27.1; (19.9 to 35.3)	27.1; (20.4 to 30.8)

3. Secondary Outcome

Title	Best Overall Response in Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab
Description	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.
Time Frame	Time from first participant randomized until 31Dec2011, cutoff date.

Outcome Measure Data

Analysis Population Description

Full Analysis Set: This set consists of all randomized participants.

Arm/Group Title	Bevacizumab, RAD001 (Everolimus)	Bevacizumab, Interferon Alfa-2a (IFN)
Arm/Group Description:	Participants received oral everolimus 10 mg qd plus intravenous bevacizumab 10mg/kg every 2 weeks.	Participants received subcutaneous IFN dose escalated from 3 MIU (million international unit) during week 1, 6 MIU during week 2, and 9 MIU during week 3 of treatment and subsequently (if tolerated), 3 times per week plus intravenous bevacizumab 10 mg/kg every 2 weeks.
Overall Number of Participants Analyzed	182	183
Measure Type: Number; Unit of Measure: Number of participants
Complete response (CR)	0	1
Partial response (PR)	49	50
Stable disease (SD)	90	84
Progressive disease (PD)	25	26
Unknown response	18	22
Overall objective response (CR+PR)	49	51

4. Secondary Outcome

Title	Response Duration Differences in Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab
Description	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.
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.

Outcome Measure Data

Analysis Population Description

A subset of participants from the full analysis set were analyzed. The full analysis set consists of all randomized participants. the subset includes participants who were complete responders or partial responders.

Arm/Group Title	Bevacizumab, RAD001 (Everolimus)	Bevacizumab, Interferon Alfa-2a (IFN)
Arm/Group Description:	Participants received oral everolimus 10 mg qd plus intravenous bevacizumab 10mg/kg every 2 weeks.	Participants received subcutaneous IFN dose escalated from 3 MIU (million international unit) during week 1, 6 MIU during week 2, and 9 MIU during week 3 of treatment and subsequently (if tolerated), 3 times per week plus intravenous bevacizumab 10 mg/kg every 2 weeks.
Overall Number of Participants Analyzed	49	51
Median (95% Confidence Interval); Unit of Measure: Months
	13.3; (10.7 to 16.7)	11.3 [1]; (10.4 to NA)

[1]

The upper limit was not estimable as it is longer than the estimated time period per data cutoff (31Dec2011).

5. Secondary Outcome

Title	Number of Participants Who Experienced Adverse Events (AEs), Serious Adverse Events and Deaths
Description	Participants were monitored for adverse events, serious adverse events and deaths throughout the study. Participants were assessed continuously at each 28-day cycle.
Time Frame	From the first participant randomized until the last patient discontinued the study treatment + 28 days

Outcome Measure Data

Analysis Population Description

Safety Set: The safety set included all participants who received at least one dose of study drug (everolimus, bevacizumab or IFN) and had a valid post-baseline assessment. No AE or occurrence of death, noted at assessment, constitutes a valid post-baseline safety assessment.

Arm/Group Title	Bevacizumab, RAD001 (Everolimus)	Bevacizumab, Interferon Alfa-2a (IFN)
Arm/Group Description:	Participants received oral everolimus 10 mg qd plus intravenous bevacizumab 10mg/kg every 2 weeks.	Participants received subcutaneous IFN dose escalated from 3 MIU (million international unit) during week 1, 6 MIU during week 2, and 9 MIU during week 3 of treatment and subsequently (if tolerated), 3 times per week plus intravenous bevacizumab 10 mg/kg every 2 weeks.
Overall Number of Participants Analyzed	180	181
Measure Type: Number; Unit of Measure: Participants
Adverse events (serious and non-serious)	179	180
Serious adverse events	79	76
Deaths	93	95

6. Secondary Outcome

Title	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
Description	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 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

Outcome Measure Data

Analysis Population Description

Full Analysis Set: This set consists of all randomized participants.

Arm/Group Title	Bevacizumab, RAD001 (Everolimus)	Bevacizumab, Interferon Alfa-2a (IFN)
Arm/Group Description:	Participants received oral everolimus 10 mg qd plus intravenous bevacizumab 10mg/kg every 2 weeks.	Participants received subcutaneous IFN dose escalated from 3 MIU (million international unit) during week 1, 6 MIU during week 2, and 9 MIU during week 3 of treatment and subsequently (if tolerated), 3 times per week plus intravenous bevacizumab 10 mg/kg every 2 weeks.
Overall Number of Participants Analyzed	182	183
Median (95% Confidence Interval); Unit of Measure: Months
	7.4; (4.7 to 10.8)	8.0; (3.7 to 11.5)

7. Secondary Outcome

Title	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%
Description	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 observed during the course of the study. A single measure reporting a decrease of at least 10% is considered definitive only if it is the last one available for the participant.
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

Outcome Measure Data

Analysis Population Description

Full Analysis Set: This set consists of all randomized participants.

Arm/Group Title	Bevacizumab, RAD001 (Everolimus)	Bevacizumab, Interferon Alfa-2a (IFN)
Arm/Group Description:	Participants received oral everolimus 10 mg qd plus intravenous bevacizumab 10mg/kg every 2 weeks.	Participants received subcutaneous IFN dose escalated from 3 MIU (million international unit) during week 1, 6 MIU during week 2, and 9 MIU during week 3 of treatment and subsequently (if tolerated), 3 times per week plus intravenous bevacizumab 10 mg/kg every 2 weeks.
Overall Number of Participants Analyzed	182	183
Median (95% Confidence Interval); Unit of Measure: Months
Global health status/QoL	7.4; (5.3 to 12.0)	7.8; (5.6 to 10.2)
Physical functioning	8.5; (5.6 to 13.8)	9.0; (6.5 to 12.9)

8. Secondary Outcome

Title	Duration of Exposure of RAD001 in Participants Randomized to the Treatment Combination of RAD001 and Bevacizumab
Description	This outcome measure was assessed continuously.
Time Frame	From the date of the first participant treated until the last patient discontinued the study treatment + 28 days

Outcome Measure Data

Analysis Population Description

Safety Set: The safety set included all participants who received at least one dose of study drug (everolimus, bevacizumab or IFN) and had a valid post-baseline assessment. No AE or occurrence of death, noted at assessment, constitutes a valid post-baseline safety assessment.

Arm/Group Title	Bevacizumab, RAD001 (Everolimus)
Arm/Group Description:	Participants received oral everolimus 10 mg qd plus intravenous bevacizumab 10mg/kg every 2 weeks.
Overall Number of Participants Analyzed	180
Median (Full Range); Unit of Measure: weeks
	37.0; (2 to 190)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Bevacizumab, RAD001 (Everolimus)	Bevacizumab, Interferon Alfa-2a (IFN)
Arm/Group Description	Participants received oral everolimus 10 mg qd plus intravenous bevacizumab 10mg/kg every 2 weeks.	Participants received subcutaneous IFN dose escalated from 3 MIU (million international unit) during week 1, 6 MIU during week 2, and 9 MIU during week 3 of treatment and subsequently (if tolerated), 3 times per week plus intravenous bevacizumab 10 mg/kg every 2 weeks.
All-Cause Mortality
	Bevacizumab, RAD001 (Everolimus)	Bevacizumab, Interferon Alfa-2a (IFN)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Bevacizumab, RAD001 (Everolimus)	Bevacizumab, Interferon Alfa-2a (IFN)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	79/180 (43.89%)	76/181 (41.99%)
Blood and lymphatic system disorders
ANAEMIA † 1	6/180 (3.33%)	8/181 (4.42%)
LEUKOPENIA † 1	1/180 (0.56%)	0/181 (0.00%)
LYMPHADENOPATHY MEDIASTINAL † 1	0/180 (0.00%)	1/181 (0.55%)
THROMBOCYTOPENIA † 1	2/180 (1.11%)	0/181 (0.00%)
Cardiac disorders
ANGINA PECTORIS † 1	1/180 (0.56%)	0/181 (0.00%)
CARDIAC ARREST † 1	1/180 (0.56%)	2/181 (1.10%)
CARDIAC FAILURE † 1	3/180 (1.67%)	0/181 (0.00%)
CARDIAC FAILURE ACUTE † 1	1/180 (0.56%)	0/181 (0.00%)
CARDIAC FAILURE CONGESTIVE † 1	3/180 (1.67%)	1/181 (0.55%)
TACHYCARDIA † 1	0/180 (0.00%)	1/181 (0.55%)
VENTRICULAR TACHYCARDIA † 1	0/180 (0.00%)	1/181 (0.55%)
Ear and labyrinth disorders
DEAFNESS † 1	0/180 (0.00%)	1/181 (0.55%)
TINNITUS † 1	1/180 (0.56%)	0/181 (0.00%)
VERTIGO † 1	0/180 (0.00%)	1/181 (0.55%)
Gastrointestinal disorders
ABDOMINAL DISTENSION † 1	1/180 (0.56%)	1/181 (0.55%)
ABDOMINAL PAIN † 1	8/180 (4.44%)	3/181 (1.66%)
ABDOMINAL PAIN UPPER † 1	0/180 (0.00%)	2/181 (1.10%)
ANAL FISSURE † 1	1/180 (0.56%)	0/181 (0.00%)
ANAL FISTULA † 1	1/180 (0.56%)	0/181 (0.00%)
ASCITES † 1	2/180 (1.11%)	0/181 (0.00%)
COLITIS † 1	0/180 (0.00%)	2/181 (1.10%)
DIARRHOEA † 1	5/180 (2.78%)	1/181 (0.55%)
DYSPHAGIA † 1	1/180 (0.56%)	0/181 (0.00%)
ENTERITIS † 1	1/180 (0.56%)	1/181 (0.55%)
FLATULENCE † 1	0/180 (0.00%)	1/181 (0.55%)
GASTRIC FISTULA † 1	1/180 (0.56%)	0/181 (0.00%)
GASTRIC ULCER † 1	1/180 (0.56%)	1/181 (0.55%)
GASTRIC ULCER HAEMORRHAGE † 1	1/180 (0.56%)	0/181 (0.00%)
GASTRITIS † 1	0/180 (0.00%)	1/181 (0.55%)
GASTROOESOPHAGEAL REFLUX DISEASE † 1	1/180 (0.56%)	0/181 (0.00%)
HAEMORRHOIDAL HAEMORRHAGE † 1	0/180 (0.00%)	1/181 (0.55%)
INTESTINAL ISCHAEMIA † 1	1/180 (0.56%)	0/181 (0.00%)
INTESTINAL OBSTRUCTION † 1	3/180 (1.67%)	1/181 (0.55%)
MOUTH HAEMORRHAGE † 1	0/180 (0.00%)	1/181 (0.55%)
NAUSEA † 1	4/180 (2.22%)	2/181 (1.10%)
PANCREATITIS † 1	1/180 (0.56%)	1/181 (0.55%)
PANCREATITIS CHRONIC † 1	1/180 (0.56%)	0/181 (0.00%)
PROCTITIS † 1	1/180 (0.56%)	0/181 (0.00%)
RECTAL HAEMORRHAGE † 1	1/180 (0.56%)	0/181 (0.00%)
RETROPERITONEUM CYST † 1	1/180 (0.56%)	0/181 (0.00%)
SIGMOIDITIS † 1	1/180 (0.56%)	0/181 (0.00%)
SMALL INTESTINAL OBSTRUCTION † 1	1/180 (0.56%)	0/181 (0.00%)
STOMATITIS † 1	3/180 (1.67%)	0/181 (0.00%)
TOOTHACHE † 1	0/180 (0.00%)	1/181 (0.55%)
UPPER GASTROINTESTINAL HAEMORRHAGE † 1	1/180 (0.56%)	0/181 (0.00%)
VOMITING † 1	4/180 (2.22%)	2/181 (1.10%)
General disorders
ASTHENIA † 1	1/180 (0.56%)	2/181 (1.10%)
DISEASE PROGRESSION † 1	1/180 (0.56%)	3/181 (1.66%)
DRUG INEFFECTIVE † 1	0/180 (0.00%)	1/181 (0.55%)
FATIGUE † 1	2/180 (1.11%)	3/181 (1.66%)
GENERAL PHYSICAL HEALTH DETERIORATION † 1	2/180 (1.11%)	4/181 (2.21%)
GENERALISED OEDEMA † 1	1/180 (0.56%)	0/181 (0.00%)
HYPERPYREXIA † 1	0/180 (0.00%)	1/181 (0.55%)
MULTI-ORGAN FAILURE † 1	0/180 (0.00%)	1/181 (0.55%)
NON-CARDIAC CHEST PAIN † 1	0/180 (0.00%)	2/181 (1.10%)
OEDEMA PERIPHERAL † 1	1/180 (0.56%)	0/181 (0.00%)
PERFORMANCE STATUS DECREASED † 1	1/180 (0.56%)	0/181 (0.00%)
PYREXIA † 1	3/180 (1.67%)	0/181 (0.00%)
SUDDEN DEATH † 1	1/180 (0.56%)	0/181 (0.00%)
Hepatobiliary disorders
BILE DUCT OBSTRUCTION † 1	0/180 (0.00%)	1/181 (0.55%)
CHOLECYSTITIS † 1	0/180 (0.00%)	1/181 (0.55%)
CHOLELITHIASIS † 1	0/180 (0.00%)	1/181 (0.55%)
CHOLESTASIS † 1	0/180 (0.00%)	1/181 (0.55%)
HEPATOTOXICITY † 1	1/180 (0.56%)	0/181 (0.00%)
JAUNDICE † 1	1/180 (0.56%)	0/181 (0.00%)
Infections and infestations
ANAL ABSCESS † 1	3/180 (1.67%)	0/181 (0.00%)
BRONCHITIS † 1	1/180 (0.56%)	0/181 (0.00%)
BRONCHOPNEUMONIA † 1	1/180 (0.56%)	1/181 (0.55%)
ESCHERICHIA URINARY TRACT INFECTION † 1	0/180 (0.00%)	1/181 (0.55%)
INJECTION SITE INFECTION † 1	0/180 (0.00%)	1/181 (0.55%)
LARYNGITIS † 1	0/180 (0.00%)	1/181 (0.55%)
LUNG INFECTION † 1	0/180 (0.00%)	1/181 (0.55%)
MYELITIS † 1	0/180 (0.00%)	1/181 (0.55%)
NECROTISING FASCIITIS † 1	1/180 (0.56%)	0/181 (0.00%)
OSTEOMYELITIS † 1	1/180 (0.56%)	1/181 (0.55%)
PHARYNGITIS † 1	1/180 (0.56%)	0/181 (0.00%)
PNEUMONIA † 1	6/180 (3.33%)	2/181 (1.10%)
PYELONEPHRITIS † 1	0/180 (0.00%)	1/181 (0.55%)
RESPIRATORY TRACT INFECTION † 1	2/180 (1.11%)	1/181 (0.55%)
SEPSIS † 1	4/180 (2.22%)	1/181 (0.55%)
SEPTIC SHOCK † 1	1/180 (0.56%)	0/181 (0.00%)
SINUSITIS BACTERIAL † 1	0/180 (0.00%)	1/181 (0.55%)
TONSILLITIS † 1	1/180 (0.56%)	0/181 (0.00%)
TUBERCULOSIS † 1	0/180 (0.00%)	1/181 (0.55%)
URINARY TRACT INFECTION † 1	1/180 (0.56%)	3/181 (1.66%)
Injury, poisoning and procedural complications
ALCOHOL POISONING † 1	1/180 (0.56%)	0/181 (0.00%)
CEMENT EMBOLISM † 1	1/180 (0.56%)	0/181 (0.00%)
CRANIOCEREBRAL INJURY † 1	1/180 (0.56%)	0/181 (0.00%)
FALL † 1	0/180 (0.00%)	1/181 (0.55%)
FEMUR FRACTURE † 1	1/180 (0.56%)	0/181 (0.00%)
FRACTURE † 1	1/180 (0.56%)	0/181 (0.00%)
HEPATIC HAEMATOMA † 1	0/180 (0.00%)	1/181 (0.55%)
INCISIONAL HERNIA † 1	1/180 (0.56%)	0/181 (0.00%)
LACERATION † 1	0/180 (0.00%)	1/181 (0.55%)
SPINAL COMPRESSION FRACTURE † 1	1/180 (0.56%)	0/181 (0.00%)
SUBDURAL HAEMATOMA † 1	1/180 (0.56%)	0/181 (0.00%)
TOXICITY TO VARIOUS AGENTS † 1	1/180 (0.56%)	1/181 (0.55%)
VASCULAR PSEUDOANEURYSM † 1	0/180 (0.00%)	1/181 (0.55%)
Investigations
BLOOD CREATINE INCREASED † 1	1/180 (0.56%)	0/181 (0.00%)
BLOOD CREATININE INCREASED † 1	3/180 (1.67%)	0/181 (0.00%)
EJECTION FRACTION DECREASED † 1	1/180 (0.56%)	0/181 (0.00%)
GAMMA-GLUTAMYLTRANSFERASE INCREASED † 1	0/180 (0.00%)	1/181 (0.55%)
HAEMOGLOBIN DECREASED † 1	1/180 (0.56%)	0/181 (0.00%)
WEIGHT DECREASED † 1	1/180 (0.56%)	2/181 (1.10%)
Metabolism and nutrition disorders
CACHEXIA † 1	1/180 (0.56%)	0/181 (0.00%)
DECREASED APPETITE † 1	3/180 (1.67%)	4/181 (2.21%)
DEHYDRATION † 1	3/180 (1.67%)	3/181 (1.66%)
DIABETES MELLITUS INADEQUATE CONTROL † 1	1/180 (0.56%)	0/181 (0.00%)
HYPERCALCAEMIA † 1	3/180 (1.67%)	1/181 (0.55%)
HYPERGLYCAEMIA † 1	1/180 (0.56%)	0/181 (0.00%)
HYPERKALAEMIA † 1	1/180 (0.56%)	1/181 (0.55%)
HYPERVOLAEMIA † 1	0/180 (0.00%)	1/181 (0.55%)
HYPOALBUMINAEMIA † 1	0/180 (0.00%)	1/181 (0.55%)
HYPOGLYCAEMIA † 1	2/180 (1.11%)	0/181 (0.00%)
HYPOKALAEMIA † 1	1/180 (0.56%)	0/181 (0.00%)
HYPONATRAEMIA † 1	3/180 (1.67%)	3/181 (1.66%)
METABOLIC ACIDOSIS † 1	1/180 (0.56%)	0/181 (0.00%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA † 1	1/180 (0.56%)	4/181 (2.21%)
BACK PAIN † 1	1/180 (0.56%)	5/181 (2.76%)
BONE LOSS † 1	1/180 (0.56%)	0/181 (0.00%)
BONE PAIN † 1	1/180 (0.56%)	1/181 (0.55%)
GROIN PAIN † 1	1/180 (0.56%)	0/181 (0.00%)
INTERVERTEBRAL DISC PROTRUSION † 1	1/180 (0.56%)	0/181 (0.00%)
MUSCULAR WEAKNESS † 1	1/180 (0.56%)	0/181 (0.00%)
PAIN IN EXTREMITY † 1	0/180 (0.00%)	1/181 (0.55%)
PATHOLOGICAL FRACTURE † 1	0/180 (0.00%)	3/181 (1.66%)
ROTATOR CUFF SYNDROME † 1	1/180 (0.56%)	0/181 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CANCER PAIN † 1	0/180 (0.00%)	1/181 (0.55%)
INTESTINAL ADENOCARCINOMA † 1	0/180 (0.00%)	1/181 (0.55%)
MALIGNANT NEOPLASM PROGRESSION † 1	0/180 (0.00%)	1/181 (0.55%)
METASTASES TO BONE † 1	1/180 (0.56%)	0/181 (0.00%)
PROSTATE CANCER † 1	1/180 (0.56%)	0/181 (0.00%)
Nervous system disorders
CEREBRAL INFARCTION † 1	1/180 (0.56%)	0/181 (0.00%)
CEREBRAL ISCHAEMIA † 1	0/180 (0.00%)	1/181 (0.55%)
CEREBROVASCULAR ACCIDENT † 1	0/180 (0.00%)	3/181 (1.66%)
COMA † 1	0/180 (0.00%)	1/181 (0.55%)
CONVULSION † 1	1/180 (0.56%)	1/181 (0.55%)
DIZZINESS † 1	1/180 (0.56%)	1/181 (0.55%)
ENCEPHALOPATHY † 1	0/180 (0.00%)	1/181 (0.55%)
EPILEPSY † 1	0/180 (0.00%)	2/181 (1.10%)
HAEMORRHAGE INTRACRANIAL † 1	1/180 (0.56%)	0/181 (0.00%)
HEADACHE † 1	2/180 (1.11%)	0/181 (0.00%)
SPINAL CORD COMPRESSION † 1	1/180 (0.56%)	1/181 (0.55%)
TRANSIENT ISCHAEMIC ATTACK † 1	0/180 (0.00%)	2/181 (1.10%)
Psychiatric disorders
ACUTE PSYCHOSIS † 1	0/180 (0.00%)	1/181 (0.55%)
ANXIETY † 1	0/180 (0.00%)	1/181 (0.55%)
CONFUSIONAL STATE † 1	0/180 (0.00%)	2/181 (1.10%)
DELIRIUM † 1	1/180 (0.56%)	0/181 (0.00%)
DEPRESSION † 1	0/180 (0.00%)	1/181 (0.55%)
MENTAL STATUS CHANGES † 1	0/180 (0.00%)	1/181 (0.55%)
SOPOR † 1	0/180 (0.00%)	1/181 (0.55%)
Renal and urinary disorders
BLADDER DILATATION † 1	0/180 (0.00%)	1/181 (0.55%)
NEPHROTIC SYNDROME † 1	1/180 (0.56%)	1/181 (0.55%)
OLIGURIA † 1	1/180 (0.56%)	0/181 (0.00%)
PROTEINURIA † 1	1/180 (0.56%)	2/181 (1.10%)
RENAL COLIC † 1	1/180 (0.56%)	0/181 (0.00%)
RENAL FAILURE † 1	5/180 (2.78%)	1/181 (0.55%)
RENAL FAILURE ACUTE † 1	2/180 (1.11%)	0/181 (0.00%)
RENAL IMPAIRMENT † 1	0/180 (0.00%)	2/181 (1.10%)
TUBULOINTERSTITIAL NEPHRITIS † 1	1/180 (0.56%)	0/181 (0.00%)
URINARY RETENTION † 1	1/180 (0.56%)	0/181 (0.00%)
Reproductive system and breast disorders
MENORRHAGIA † 1	1/180 (0.56%)	0/181 (0.00%)
TESTICULAR PAIN † 1	1/180 (0.56%)	0/181 (0.00%)
Respiratory, thoracic and mediastinal disorders
ACUTE PULMONARY OEDEMA † 1	1/180 (0.56%)	0/181 (0.00%)
ATELECTASIS † 1	0/180 (0.00%)	1/181 (0.55%)
BRONCHOSPASM † 1	1/180 (0.56%)	0/181 (0.00%)
CHRONIC OBSTRUCTIVE PULMONARY DISEASE † 1	2/180 (1.11%)	0/181 (0.00%)
COUGH † 1	1/180 (0.56%)	0/181 (0.00%)
DYSPNOEA † 1	6/180 (3.33%)	3/181 (1.66%)
DYSPNOEA EXERTIONAL † 1	0/180 (0.00%)	1/181 (0.55%)
EMPHYSEMA † 1	0/180 (0.00%)	1/181 (0.55%)
EPISTAXIS † 1	5/180 (2.78%)	0/181 (0.00%)
HAEMOPTYSIS † 1	2/180 (1.11%)	2/181 (1.10%)
PLEURAL EFFUSION † 1	3/180 (1.67%)	2/181 (1.10%)
PNEUMONIA ASPIRATION † 1	1/180 (0.56%)	0/181 (0.00%)
PNEUMONITIS † 1	1/180 (0.56%)	0/181 (0.00%)
PULMONARY EMBOLISM † 1	1/180 (0.56%)	2/181 (1.10%)
PULMONARY OEDEMA † 1	1/180 (0.56%)	1/181 (0.55%)
RESPIRATORY FAILURE † 1	1/180 (0.56%)	0/181 (0.00%)
SLEEP APNOEA SYNDROME † 1	1/180 (0.56%)	0/181 (0.00%)
Vascular disorders
ACCELERATED HYPERTENSION † 1	0/180 (0.00%)	1/181 (0.55%)
CIRCULATORY COLLAPSE † 1	1/180 (0.56%)	0/181 (0.00%)
HYPERTENSION † 1	4/180 (2.22%)	3/181 (1.66%)
HYPERTENSIVE CRISIS † 1	2/180 (1.11%)	2/181 (1.10%)
HYPOTENSION † 1	1/180 (0.56%)	0/181 (0.00%)
HYPOVOLAEMIC SHOCK † 1	1/180 (0.56%)	0/181 (0.00%)
THROMBOSIS † 1	0/180 (0.00%)	1/181 (0.55%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Bevacizumab, RAD001 (Everolimus)	Bevacizumab, Interferon Alfa-2a (IFN)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	173/180 (96.11%)	179/181 (98.90%)
Blood and lymphatic system disorders
ANAEMIA † 1	35/180 (19.44%)	35/181 (19.34%)
LEUKOPENIA † 1	4/180 (2.22%)	12/181 (6.63%)
LYMPHOPENIA † 1	4/180 (2.22%)	11/181 (6.08%)
NEUTROPENIA † 1	7/180 (3.89%)	21/181 (11.60%)
THROMBOCYTOPENIA † 1	16/180 (8.89%)	29/181 (16.02%)
Cardiac disorders
TACHYCARDIA † 1	9/180 (5.00%)	2/181 (1.10%)
Gastrointestinal disorders
ABDOMINAL PAIN † 1	18/180 (10.00%)	19/181 (10.50%)
ABDOMINAL PAIN UPPER † 1	10/180 (5.56%)	9/181 (4.97%)
CONSTIPATION † 1	30/180 (16.67%)	26/181 (14.36%)
DIARRHOEA † 1	71/180 (39.44%)	47/181 (25.97%)
DRY MOUTH † 1	3/180 (1.67%)	11/181 (6.08%)
DYSPEPSIA † 1	8/180 (4.44%)	11/181 (6.08%)
GINGIVAL BLEEDING † 1	3/180 (1.67%)	11/181 (6.08%)
MOUTH ULCERATION † 1	13/180 (7.22%)	3/181 (1.66%)
NAUSEA † 1	38/180 (21.11%)	50/181 (27.62%)
STOMATITIS † 1	111/180 (61.67%)	42/181 (23.20%)
TOOTHACHE † 1	16/180 (8.89%)	12/181 (6.63%)
VOMITING † 1	25/180 (13.89%)	26/181 (14.36%)
General disorders
ASTHENIA † 1	39/180 (21.67%)	62/181 (34.25%)
CHILLS † 1	4/180 (2.22%)	21/181 (11.60%)
FATIGUE † 1	57/180 (31.67%)	75/181 (41.44%)
INFLUENZA LIKE ILLNESS † 1	5/180 (2.78%)	32/181 (17.68%)
MALAISE † 1	2/180 (1.11%)	11/181 (6.08%)
OEDEMA PERIPHERAL † 1	44/180 (24.44%)	18/181 (9.94%)
PYREXIA † 1	24/180 (13.33%)	63/181 (34.81%)
Infections and infestations
GINGIVITIS † 1	10/180 (5.56%)	7/181 (3.87%)
INFLUENZA † 1	10/180 (5.56%)	5/181 (2.76%)
SINUSITIS † 1	10/180 (5.56%)	6/181 (3.31%)
UPPER RESPIRATORY TRACT INFECTION † 1	18/180 (10.00%)	7/181 (3.87%)
URINARY TRACT INFECTION † 1	16/180 (8.89%)	16/181 (8.84%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED † 1	9/180 (5.00%)	4/181 (2.21%)
ASPARTATE AMINOTRANSFERASE INCREASED † 1	10/180 (5.56%)	5/181 (2.76%)
BLOOD CREATININE INCREASED † 1	20/180 (11.11%)	7/181 (3.87%)
GAMMA-GLUTAMYLTRANSFERASE INCREASED † 1	10/180 (5.56%)	13/181 (7.18%)
WEIGHT DECREASED † 1	51/180 (28.33%)	58/181 (32.04%)
Metabolism and nutrition disorders
DECREASED APPETITE † 1	48/180 (26.67%)	80/181 (44.20%)
HYPERCHOLESTEROLAEMIA † 1	40/180 (22.22%)	8/181 (4.42%)
HYPERGLYCAEMIA † 1	18/180 (10.00%)	5/181 (2.76%)
HYPERKALAEMIA † 1	5/180 (2.78%)	11/181 (6.08%)
HYPERTRIGLYCERIDAEMIA † 1	24/180 (13.33%)	17/181 (9.39%)
HYPERURICAEMIA † 1	3/180 (1.67%)	14/181 (7.73%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA † 1	33/180 (18.33%)	37/181 (20.44%)
BACK PAIN † 1	22/180 (12.22%)	26/181 (14.36%)
BONE PAIN † 1	8/180 (4.44%)	10/181 (5.52%)
MUSCULOSKELETAL CHEST PAIN † 1	9/180 (5.00%)	11/181 (6.08%)
MYALGIA † 1	11/180 (6.11%)	34/181 (18.78%)
PAIN IN EXTREMITY † 1	25/180 (13.89%)	17/181 (9.39%)
Nervous system disorders
DIZZINESS † 1	11/180 (6.11%)	12/181 (6.63%)
DYSGEUSIA † 1	21/180 (11.67%)	7/181 (3.87%)
HEADACHE † 1	36/180 (20.00%)	38/181 (20.99%)
Psychiatric disorders
DEPRESSION † 1	8/180 (4.44%)	25/181 (13.81%)
INSOMNIA † 1	23/180 (12.78%)	25/181 (13.81%)
Renal and urinary disorders
DYSURIA † 1	10/180 (5.56%)	10/181 (5.52%)
PROTEINURIA † 1	90/180 (50.00%)	68/181 (37.57%)
Respiratory, thoracic and mediastinal disorders
COUGH † 1	54/180 (30.00%)	34/181 (18.78%)
DYSPHONIA † 1	11/180 (6.11%)	9/181 (4.97%)
DYSPNOEA † 1	28/180 (15.56%)	32/181 (17.68%)
EPISTAXIS † 1	62/180 (34.44%)	38/181 (20.99%)
OROPHARYNGEAL PAIN † 1	18/180 (10.00%)	7/181 (3.87%)
PNEUMONITIS † 1	12/180 (6.67%)	1/181 (0.55%)
RHINORRHOEA † 1	13/180 (7.22%)	9/181 (4.97%)
Skin and subcutaneous tissue disorders
DERMATITIS † 1	13/180 (7.22%)	2/181 (1.10%)
DERMATITIS ACNEIFORM † 1	9/180 (5.00%)	1/181 (0.55%)
DRY SKIN † 1	22/180 (12.22%)	16/181 (8.84%)
PRURITUS † 1	31/180 (17.22%)	22/181 (12.15%)
RASH † 1	42/180 (23.33%)	20/181 (11.05%)
Vascular disorders
HYPERTENSION † 1	67/180 (37.22%)	39/181 (21.55%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.

Results Point of Contact

• Name/Title: Study Director
• Organization: Novartis Pharmaceuticals
• Phone: 862-778-8300

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ravaud A, Barrios CH, Alekseev B, Tay MH, Agarwala SS, Yalcin S, Lin CC, Roman L, Shkolnik M, Anak O, Gogov S, Pelov D, Louveau AL, Melichar B. RECORD-2: phase II randomized study of everolimus and bevacizumab versus interferon α-2a and bevacizumab as first-line therapy in patients with metastatic renal cell carcinoma. Ann Oncol. 2015 Jul;26(7):1378-84. doi: 10.1093/annonc/mdv170. Epub 2015 Apr 7.

• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• ClinicalTrials.gov Identifier: NCT00719264
• Other Study ID Numbers: CRAD001L2201; 2008-000077-38 ( EudraCT Number )
• First Submitted: July 15, 2008
• First Posted: July 21, 2008
• Results First Submitted: April 4, 2014
• Results First Posted: May 7, 2014
• Last Update Posted: March 20, 2017