Study Comparing Bevacizumab + Temsirolimus vs. Bevacizumab + Interferon-Alfa In Advanced Renal Cell Carcinoma Subjects (INTORACT)

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: NCT00631371

Recruitment Status : Completed

First Posted : March 7, 2008

Results First Posted : June 4, 2013

Last Update Posted : April 27, 2016

Sponsor:

Information provided by (Responsible Party):

Pfizer

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Renal Cell Carcinoma
Interventions	Drug: Bevacizumab Drug: Temsirolimus Drug: Interferon-Alfa 9MU
Enrollment	791

Participant Flow

Recruitment Details	Approximately 800 participants enrolled in this study at 200 sites.
Pre-assignment Details	Participants were randomized in a 1:1 ratio, stratified by prior nephrectomy status (yes/no) and Memorial Sloan Kettering Cancer Center (MSKCC) risk factors (good/intermediate/poor), and received either the combination treatment of Temisirolimus + Bevacizumab (Temsr+Bev) or Interferon-alfa + Bevacizumab (IFN+Bev).


Arm/Group Title	Bevacizumab+Temsirolimus	Bevacizumab+ Interferon-Alfa
Arm/Group Description	Bevacizumab 10 milligram per kilogr...	Bevacizumab 10 mg/kg intravenous in...
Arm/Group Description	Bevacizumab 10 milligram per kilogram (mg/kg) intravenous infusion over 90 minutes, 60 minutes or 30 minutes depending on the participant's tolerability every other week along with temsirolimus 25 mg intravenous infusion over at least 30 minutes once a week. Treatment was continued until disease progression, unacceptable toxicities, withdrawal of consent, or death.	Bevacizumab 10 mg/kg intravenous infusion over 90 minutes, 60 minutes or 30 minutes depending on the participant's tolerability every other week along with interferon-alfa (IFN) 9 million units (MU) subcutaneous injection every 3 times a week. Treatment was continued until disease progression, unacceptable toxicities, withdrawal of consent, or death.
Period Title: Overall Study
Started	400	391
Treated	393	391
Completed	0	0
Not Completed	400	391
Reason Not Completed
Lost to Follow-up	24	19
Other reason	5	12
subject request	38	45
Discontinuation of study by Sponsor	70	76
Death	263	239

Baseline Characteristics

Arm/Group Title		Bevacizumab+Temsirolimus	Bevacizumab+ Interferon-Alfa	Total
Arm/Group Description		Bevacizumab 10 milligram per kilogr...	Bevacizumab 10 mg/kg intravenous in...	Total of all reporting groups
Arm/Group Description		Bevacizumab 10 milligram per kilogram (mg/kg) intravenous infusion over 90 minutes, 60 minutes or 30 minutes depending on the participant's tolerability every other week along with temsirolimus 25 mg intravenous infusion over at least 30 minutes once a week. Treatment was continued until disease progression, unacceptable toxicities, withdrawal of consent, or death.	Bevacizumab 10 mg/kg intravenous infusion over 90 minutes, 60 minutes or 30 minutes depending on the participant's tolerability every other week along with interferon-alfa (IFN) 9 million units (MU) subcutaneous injection every 3 times a week. Treatment was continued until disease progression, unacceptable toxicities, withdrawal of consent, or death.	Total of all reporting groups
Overall Number of Baseline Participants		400	391	791
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	400 participants	391 participants	791 participants
		58.6 (10.1)	58.2 (10.4)	58.4 (10.2)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	400 participants	391 participants	791 participants
	Female	114 28.5%	121 30.9%	235 29.7%
	Male	286 71.5%	270 69.1%	556 70.3%

Outcome Measures

1.Primary Outcome


Title	Progression-Free Survival (PFS): Independent-Assessment
Description	PFS was defined as the interval from the date of randomization until t...
Description	PFS was defined as the interval from the date of randomization until the earlier date of progression or death. Progression was assessed by independent imaging reviewers using Response Evaluation Criteria in Solid Tumors (RECIST) criteria which is 20% increase in sum of longest diameter of target lesions from nadir (the lowest blood counts); measurable increase in non-target lesion; appearance of new lesions.
Time Frame	Baseline until disease progression, initiation of new anticancer treatment, or death, assessed every 8 weeks (up to cut-off date: 19 April 2012)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all participants who were randomized to the study.


Arm/Group Title	Bevacizumab+Temsirolimus	Bevacizumab+ Interferon-Alfa
Arm/Group Description:	Bevacizumab 10 milligram per kilogr...	Bevacizumab 10 mg/kg intravenous in...
Arm/Group Description:	Bevacizumab 10 milligram per kilogram (mg/kg) intravenous infusion over 90 minutes, 60 minutes or 30 minutes depending on the participant's tolerability every other week along with temsirolimus 25 mg intravenous infusion over at least 30 minutes once a week. Treatment was continued until disease progression, unacceptable toxicities, withdrawal of consent, or death.	Bevacizumab 10 mg/kg intravenous infusion over 90 minutes, 60 minutes or 30 minutes depending on the participant's tolerability every other week along with interferon-alfa (IFN) 9 million units (MU) subcutaneous injection every 3 times a week. Treatment was continued until disease progression, unacceptable toxicities, withdrawal of consent, or death.
Overall Number of Participants Analyzed	400	391
Median (95% Confidence Interval) Unit of Measure: months
	9.1 (8.1 to 10.2)	9.3 (9.0 to 11.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab+Temsirolimus, Bevacizumab+ Interferon-Alfa
	Comments	P value was based on 1-sided stratified log-rank test (stratification factors: prior nephrectomy [yes/no] and Memorial Sloan Kettering Cancer Center [MSKCC] risk factors [good/intermediate/poor] at time of randomization). The hazard ratio and corresponding 95 percent (%) confidence interval (CI) from the stratified cox proportional hazard model were also presented.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.8
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95% 0.9 to 1.3
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Progression-Free Survival (PFS): Investigator-Assessment
Description	PFS was defined as the interval from the date of randomization until t...
Description	PFS was defined as the interval from the date of randomization until the earlier date of progression or death. Progression was assessed by investigator imaging reviewers using RECIST criteria which is 20% increase in sum of longest diameter of target lesions from nadir (the lowest blood counts); measurable increase in non-target lesion; appearance of new lesions.
Time Frame	Baseline until disease progression, initiation of new anticancer treatment, or death, assessed every 8 weeks (up to cut-off date: 19 April 2012)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized to the study.


Arm/Group Title	Bevacizumab+Temsirolimus	Bevacizumab+ Interferon-Alfa
Arm/Group Description:	Bevacizumab 10 milligram per kilogr...	Bevacizumab 10 mg/kg intravenous in...
Arm/Group Description:	Bevacizumab 10 milligram per kilogram (mg/kg) intravenous infusion over 90 minutes, 60 minutes or 30 minutes depending on the participant's tolerability every other week along with temsirolimus 25 mg intravenous infusion over at least 30 minutes once a week. Treatment was continued until disease progression, unacceptable toxicities, withdrawal of consent, or death.	Bevacizumab 10 mg/kg intravenous infusion over 90 minutes, 60 minutes or 30 minutes depending on the participant's tolerability every other week along with interferon-alfa (IFN) 9 million units (MU) subcutaneous injection every 3 times a week. Treatment was continued until disease progression, unacceptable toxicities, withdrawal of consent, or death.
Overall Number of Participants Analyzed	400	391
Median (95% Confidence Interval) Unit of Measure: months
	9.1 (8.1 to 10.5)	10.8 (9.1 to 11.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab+Temsirolimus, Bevacizumab+ Interferon-Alfa
	Comments	P-value was based on 1-sided stratified log-rank test (stratification factors: prior nephrectomy [yes/no] and MSKCC risk factors [good/intermediate/poor] at time of randomization). The hazard ratio and corresponding 95% CI from the stratified cox proportional hazard model were also presented.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.9
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95% 1.0 to 1.4
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Percentage of Participants With Objective Response (Complete Response/Partial Response): Independent-Assessment
Description	Percentage of participants with OR based assessment of confirmed compl...
Description	Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed response were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and/or non target). PR were those with at least 30% decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent.
Time Frame	Baseline until disease progression, initiation of new anticancer treatment, or death, assessed every 8 weeks (up to cut-off date: 19 April 2012)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized to the study.


Arm/Group Title	Bevacizumab+Temsirolimus	Bevacizumab+ Interferon-Alfa
Arm/Group Description:	Bevacizumab 10 milligram per kilogr...	Bevacizumab 10 mg/kg intravenous in...
Arm/Group Description:	Bevacizumab 10 milligram per kilogram (mg/kg) intravenous infusion over 90 minutes, 60 minutes or 30 minutes depending on the participant's tolerability every other week along with temsirolimus 25 mg intravenous infusion over at least 30 minutes once a week. Treatment was continued until disease progression, unacceptable toxicities, withdrawal of consent, or death.	Bevacizumab 10 mg/kg intravenous infusion over 90 minutes, 60 minutes or 30 minutes depending on the participant's tolerability every other week along with interferon-alfa (IFN) 9 million units (MU) subcutaneous injection every 3 times a week. Treatment was continued until disease progression, unacceptable toxicities, withdrawal of consent, or death.
Overall Number of Participants Analyzed	400	391
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	27.0 (22.7 to 31.6)	27.4 (23.0 to 32.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab+Temsirolimus, Bevacizumab+ Interferon-Alfa
	Comments	P-value (2-sided), risk ratio and associated 95% CI were based on Cochran-Mantel-Haenszel test stratified by prior nephrectomy and MSKCC risk group as randomized.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	1.0
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95% 0.8 to 1.3
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Overall Survival (OS)
Description	OS was defined as the time from randomization to death due to any caus...
Description	OS was defined as the time from randomization to death due to any cause, censored at the last date known alive. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).
Time Frame	Baseline until death due to any cause, assessed every 8 weeks (up to cut-off date: 19 April 2012)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized to the study.


Arm/Group Title	Bevacizumab+Temsirolimus	Bevacizumab+ Interferon-Alfa
Arm/Group Description:	Bevacizumab 10 milligram per kilogr...	Bevacizumab 10 mg/kg intravenous in...
Arm/Group Description:	Bevacizumab 10 milligram per kilogram (mg/kg) intravenous infusion over 90 minutes, 60 minutes or 30 minutes depending on the participant's tolerability every other week along with temsirolimus 25 mg intravenous infusion over at least 30 minutes once a week. Treatment was continued until disease progression, unacceptable toxicities, withdrawal of consent, or death.	Bevacizumab 10 mg/kg intravenous infusion over 90 minutes, 60 minutes or 30 minutes depending on the participant's tolerability every other week along with interferon-alfa (IFN) 9 million units (MU) subcutaneous injection every 3 times a week. Treatment was continued until disease progression, unacceptable toxicities, withdrawal of consent, or death.
Overall Number of Participants Analyzed	400	391
Median (95% Confidence Interval) Unit of Measure: months
	25.8 (21.1 to 30.7)	25.5 (22.4 to 30.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab+Temsirolimus, Bevacizumab+ Interferon-Alfa
	Comments	P value was based on 1-sided stratified log-rank test (stratification factors: prior nephrectomy [yes/no] and MSKCC risk factors [good/intermediate/poor] at time of randomization). The hazard ratio and corresponding 95% CI from the stratified cox proportional hazard model were also presented.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.6
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95% 0.9 to 1.3
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Adverse events were collected and reported from the signing of the informed consent until end of treatment but no later than 30 days after the last dose of study medication.
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Arm/Group Title	Bevacizumab+Temsirolimus	Bevacizumab+ Interferon-Alfa
Arm/Group Description	Bevacizumab 10 milligram per kilogr...	Bevacizumab 10 mg/kg intravenous in...
Arm/Group Description	Bevacizumab 10 milligram per kilogram (mg/kg) intravenous infusion over 90 minutes, 60 minutes or 30 minutes depending on the participant's tolerability every other week along with temsirolimus 25 mg intravenous infusion over at least 30 minutes once a week. Treatment was continued until disease progression, unacceptable toxicities, withdrawal of consent, or death.	Bevacizumab 10 mg/kg intravenous infusion over 90 minutes, 60 minutes or 30 minutes depending on the participant's tolerability every other week along with interferon-alfa (IFN) 9 million units (MU) subcutaneous injection every 3 times a week. Treatment was continued until disease progression, unacceptable toxicities, withdrawal of consent, or death.
All-Cause Mortality
	Bevacizumab+Temsirolimus	Bevacizumab+ Interferon-Alfa
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Bevacizumab+Temsirolimus	Bevacizumab+ Interferon-Alfa
	Affected / at Risk (%)	Affected / at Risk (%)
Total	184/393 (46.82%)	158/391 (40.41%)
Blood and lymphatic system disorders
Anaemia ^* 1	10/393 (2.54%)	12/391 (3.07%)
Disseminated intravascular coagulation ^* 1	0/393 (0.00%)	1/391 (0.26%)
Neutropenia ^* 1	0/393 (0.00%)	1/391 (0.26%)
Thrombocytopenia ^* 1	0/393 (0.00%)	1/391 (0.26%)
Cardiac disorders
Acute coronary syndrome ^* 1	1/393 (0.25%)	0/391 (0.00%)
Acute myocardial infarction ^* 1	1/393 (0.25%)	1/391 (0.26%)
Angina pectoris ^* 1	0/393 (0.00%)	1/391 (0.26%)
Atrial fibrillation ^* 1	0/393 (0.00%)	1/391 (0.26%)
Cardiac failure ^* 1	3/393 (0.76%)	0/391 (0.00%)
Cardiac valve disease ^* 1	1/393 (0.25%)	0/391 (0.00%)
Cardiopulmonary failure ^* 1	1/393 (0.25%)	1/391 (0.26%)
Coronary artery disease ^* 1	1/393 (0.25%)	0/391 (0.00%)
Coronary ostial stenosis ^* 1	0/393 (0.00%)	1/391 (0.26%)
Left ventricular dysfunction ^* 1	0/393 (0.00%)	1/391 (0.26%)
Cardio-Respiratory Arrest ^* 1	0/393 (0.00%)	1/391 (0.26%)
Ear and labyrinth disorders
Vertigo ^* 1	0/393 (0.00%)	1/391 (0.26%)
Eye disorders
Retinopathy ^* 1	0/393 (0.00%)	2/391 (0.51%)
Vitreous floaters ^* 1	0/393 (0.00%)	1/391 (0.26%)
Gastrointestinal disorders
Abdominal pain ^* 1	8/393 (2.04%)	6/391 (1.53%)
Anal fissure ^* 1	2/393 (0.51%)	0/391 (0.00%)
Anal fistula ^* 1	2/393 (0.51%)	2/391 (0.51%)
Anal haemorrhage ^* 1	1/393 (0.25%)	0/391 (0.00%)
Ascites ^* 1	0/393 (0.00%)	1/391 (0.26%)
Colitis ^* 1	2/393 (0.51%)	0/391 (0.00%)
Constipation ^* 1	0/393 (0.00%)	1/391 (0.26%)
Diarrhoea ^* 1	7/393 (1.78%)	5/391 (1.28%)
Gastric fistula ^* 1	0/393 (0.00%)	1/391 (0.26%)
Gastric ulcer haemorrhage ^* 1	1/393 (0.25%)	0/391 (0.00%)
Gastritis ^* 1	2/393 (0.51%)	0/391 (0.00%)
Gastrointestinal haemorrhage ^* 1	0/393 (0.00%)	1/391 (0.26%)
Gastrointestinal perforation ^* 1	0/393 (0.00%)	1/391 (0.26%)
Gastrooesophageal reflux disease ^* 1	1/393 (0.25%)	0/391 (0.00%)
Haemorrhoidal haemorrhage ^* 1	0/393 (0.00%)	1/391 (0.26%)
Haemorrhoids ^* 1	1/393 (0.25%)	0/391 (0.00%)
Ileal perforation ^* 1	1/393 (0.25%)	0/391 (0.00%)
Ileus ^* 1	1/393 (0.25%)	1/391 (0.26%)
Ileus paralytic ^* 1	1/393 (0.25%)	0/391 (0.00%)
Intestinal haemorrhage ^* 1	0/393 (0.00%)	1/391 (0.26%)
Intestinal obstruction ^* 1	2/393 (0.51%)	0/391 (0.00%)
Intestinal perforation ^* 1	1/393 (0.25%)	1/391 (0.26%)
Large intestine perforation ^* 1	2/393 (0.51%)	1/391 (0.26%)
Lower gastrointestinal haemorrhage ^* 1	1/393 (0.25%)	0/391 (0.00%)
Mouth ulceration ^* 1	1/393 (0.25%)	0/391 (0.00%)
Nausea ^* 1	1/393 (0.25%)	0/391 (0.00%)
Painful defaecation ^* 1	1/393 (0.25%)	0/391 (0.00%)
Pancreatitis ^* 1	2/393 (0.51%)	2/391 (0.51%)
Pancreatitis acute ^* 1	1/393 (0.25%)	1/391 (0.26%)
Proctitis ^* 1	1/393 (0.25%)	0/391 (0.00%)
Rectal haemorrhage ^* 1	0/393 (0.00%)	1/391 (0.26%)
Small intestinal obstruction ^* 1	0/393 (0.00%)	1/391 (0.26%)
Stomatitis ^* 1	1/393 (0.25%)	1/391 (0.26%)
Subileus ^* 1	0/393 (0.00%)	1/391 (0.26%)
Upper gastrointestinal haemorrhage ^* 1	1/393 (0.25%)	2/391 (0.51%)
Vomiting ^* 1	7/393 (1.78%)	2/391 (0.51%)
General disorders
Asthenia ^* 1	4/393 (1.02%)	5/391 (1.28%)
Chills ^* 1	0/393 (0.00%)	1/391 (0.26%)
Death ^* 1	0/393 (0.00%)	4/391 (1.02%)
Disease progression ^* 1	13/393 (3.31%)	16/391 (4.09%)
Fatigue ^* 1	1/393 (0.25%)	7/391 (1.79%)
General physical health deterioration ^* 1	2/393 (0.51%)	6/391 (1.53%)
Injury associated with device ^* 1	0/393 (0.00%)	1/391 (0.26%)
Mucosal inflammation ^* 1	5/393 (1.27%)	0/391 (0.00%)
Multi-organ failure ^* 1	2/393 (0.51%)	0/391 (0.00%)
Non-cardiac chest pain ^* 1	0/393 (0.00%)	1/391 (0.26%)
Oedema peripheral ^* 1	1/393 (0.25%)	0/391 (0.00%)
Pain ^* 1	1/393 (0.25%)	2/391 (0.51%)
Pyrexia ^* 1	9/393 (2.29%)	7/391 (1.79%)
Sudden death ^* 1	5/393 (1.27%)	0/391 (0.00%)
Condition Aggravated ^* 1	1/393 (0.25%)	0/391 (0.00%)
Hepatobiliary disorders
Acute hepatic failure ^* 1	0/393 (0.00%)	1/391 (0.26%)
Cholangitis ^* 1	0/393 (0.00%)	1/391 (0.26%)
Cholecystitis ^* 1	3/393 (0.76%)	0/391 (0.00%)
Cholecystitis acute ^* 1	1/393 (0.25%)	0/391 (0.00%)
Cholecystitis chronic ^* 1	0/393 (0.00%)	1/391 (0.26%)
Cholelithiasis ^* 1	0/393 (0.00%)	1/391 (0.26%)
Hepatitis toxic ^* 1	0/393 (0.00%)	1/391 (0.26%)
Immune system disorders
Contrast media allergy ^* 1	0/393 (0.00%)	1/391 (0.26%)
Drug hypersensitivity ^* 1	1/393 (0.25%)	0/391 (0.00%)
Infections and infestations
Abdominal abscess ^* 1	0/393 (0.00%)	1/391 (0.26%)
Abscess ^* 1	0/393 (0.00%)	1/391 (0.26%)
Abscess intestinal ^* 1	0/393 (0.00%)	1/391 (0.26%)
Anal abscess ^* 1	5/393 (1.27%)	2/391 (0.51%)
Anorectal cellulitis ^* 1	1/393 (0.25%)	0/391 (0.00%)
Appendicitis ^* 1	1/393 (0.25%)	1/391 (0.26%)
Bronchitis ^* 1	0/393 (0.00%)	1/391 (0.26%)
Bronchopneumonia ^* 1	3/393 (0.76%)	1/391 (0.26%)
Cellulitis ^* 1	0/393 (0.00%)	1/391 (0.26%)
Cystitis ^* 1	0/393 (0.00%)	1/391 (0.26%)
Diarrhoea infectious ^* 1	1/393 (0.25%)	0/391 (0.00%)
Erysipelas ^* 1	1/393 (0.25%)	0/391 (0.00%)
Gangrene ^* 1	1/393 (0.25%)	0/391 (0.00%)
Gastroenteritis viral ^* 1	0/393 (0.00%)	1/391 (0.26%)
Haematoma infection ^* 1	0/393 (0.00%)	1/391 (0.26%)
Haemorrhoid infection ^* 1	1/393 (0.25%)	0/391 (0.00%)
Infection ^* 1	1/393 (0.25%)	1/391 (0.26%)
Infectious pleural effusion ^* 1	2/393 (0.51%)	0/391 (0.00%)
Injection site infection ^* 1	0/393 (0.00%)	1/391 (0.26%)
Liver abscess ^* 1	1/393 (0.25%)	0/391 (0.00%)
Lower respiratory tract infection ^* 1	1/393 (0.25%)	1/391 (0.26%)
Lung abscess ^* 1	2/393 (0.51%)	0/391 (0.00%)
Osteomyelitis chronic ^* 1	1/393 (0.25%)	0/391 (0.00%)
Perirectal abscess ^* 1	2/393 (0.51%)	0/391 (0.00%)
Peritoneal abscess ^* 1	1/393 (0.25%)	0/391 (0.00%)
Peritonitis ^* 1	3/393 (0.76%)	2/391 (0.51%)
Pharyngitis ^* 1	2/393 (0.51%)	0/391 (0.00%)
Pneumonia ^* 1	16/393 (4.07%)	5/391 (1.28%)
Post procedural infection ^* 1	0/393 (0.00%)	1/391 (0.26%)
Rectal abscess ^* 1	1/393 (0.25%)	0/391 (0.00%)
Respiratory tract infection ^* 1	2/393 (0.51%)	1/391 (0.26%)
Scrotal abscess ^* 1	0/393 (0.00%)	1/391 (0.26%)
Sepsis ^* 1	2/393 (0.51%)	4/391 (1.02%)
Septic shock ^* 1	1/393 (0.25%)	2/391 (0.51%)
Sinusitis ^* 1	2/393 (0.51%)	0/391 (0.00%)
Subcutaneous abscess ^* 1	1/393 (0.25%)	1/391 (0.26%)
Tooth infection ^* 1	2/393 (0.51%)	0/391 (0.00%)
Urinary tract infection ^* 1	5/393 (1.27%)	4/391 (1.02%)
Urosepsis ^* 1	1/393 (0.25%)	0/391 (0.00%)
Viral infection ^* 1	1/393 (0.25%)	0/391 (0.00%)
Viral pharyngitis ^* 1	1/393 (0.25%)	0/391 (0.00%)
Colonic abscess ^* 1	0/393 (0.00%)	1/391 (0.26%)
Epididymitis ^* 1	0/393 (0.00%)	1/391 (0.26%)
Plasmodium Malariae Infection ^* 1	1/393 (0.25%)	0/391 (0.00%)
Pulmonary Tuberculosis ^* 1	1/393 (0.25%)	0/391 (0.00%)
Pyelonephritis Acute ^* 1	0/393 (0.00%)	1/391 (0.26%)
Injury, poisoning and procedural complications
Femoral neck fracture ^* 1	0/393 (0.00%)	1/391 (0.26%)
Femur fracture ^* 1	1/393 (0.25%)	1/391 (0.26%)
Head injury ^* 1	0/393 (0.00%)	1/391 (0.26%)
Humerus fracture ^* 1	1/393 (0.25%)	0/391 (0.00%)
Incisional hernia ^* 1	1/393 (0.25%)	0/391 (0.00%)
Post procedural fistula ^* 1	1/393 (0.25%)	0/391 (0.00%)
Seroma ^* 1	1/393 (0.25%)	0/391 (0.00%)
Thoracic vertebral fracture ^* 1	0/393 (0.00%)	2/391 (0.51%)
Ulna fracture ^* 1	0/393 (0.00%)	1/391 (0.26%)
Wound complication ^* 1	0/393 (0.00%)	1/391 (0.26%)
Investigations
Blood pressure systolic decreased ^* 1	1/393 (0.25%)	0/391 (0.00%)
Fibrin D dimer increased ^* 1	1/393 (0.25%)	0/391 (0.00%)
Haemoglobin decreased ^* 1	0/393 (0.00%)	2/391 (0.51%)
Protein urine present ^* 1	0/393 (0.00%)	1/391 (0.26%)
Weight decreased ^* 1	0/393 (0.00%)	1/391 (0.26%)
Blood Bilirubin Increased ^* 1	1/393 (0.25%)	0/391 (0.00%)
Blood Creatinine Increased ^* 1	1/393 (0.25%)	0/391 (0.00%)
Metabolism and nutrition disorders
Decreased appetite ^* 1	2/393 (0.51%)	0/391 (0.00%)
Dehydration ^* 1	4/393 (1.02%)	3/391 (0.77%)
Diabetes mellitus ^* 1	1/393 (0.25%)	1/391 (0.26%)
Diabetes mellitus inadequate control ^* 1	1/393 (0.25%)	0/391 (0.00%)
Fluid retention ^* 1	1/393 (0.25%)	0/391 (0.00%)
Gout ^* 1	0/393 (0.00%)	1/391 (0.26%)
Hypercalcaemia ^* 1	3/393 (0.76%)	2/391 (0.51%)
Hyperglycaemia ^* 1	4/393 (1.02%)	0/391 (0.00%)
Hyperkalaemia ^* 1	1/393 (0.25%)	3/391 (0.77%)
Hypoalbuminaemia ^* 1	1/393 (0.25%)	0/391 (0.00%)
Hyponatraemia ^* 1	3/393 (0.76%)	2/391 (0.51%)
Hypophagia ^* 1	1/393 (0.25%)	0/391 (0.00%)
Ketosis ^* 1	1/393 (0.25%)	0/391 (0.00%)
Tumour lysis syndrome ^* 1	1/393 (0.25%)	0/391 (0.00%)
Type 2 diabetes mellitus ^* 1	1/393 (0.25%)	0/391 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia ^* 1	3/393 (0.76%)	1/391 (0.26%)
Back pain ^* 1	3/393 (0.76%)	3/391 (0.77%)
Bone lesion ^* 1	0/393 (0.00%)	1/391 (0.26%)
Bone pain ^* 1	1/393 (0.25%)	0/391 (0.00%)
Fistula ^* 1	0/393 (0.00%)	1/391 (0.26%)
Flank pain ^* 1	0/393 (0.00%)	1/391 (0.26%)
Gouty arthritis ^* 1	0/393 (0.00%)	1/391 (0.26%)
Muscular weakness ^* 1	2/393 (0.51%)	2/391 (0.51%)
Musculoskeletal chest pain ^* 1	1/393 (0.25%)	1/391 (0.26%)
Myalgia ^* 1	0/393 (0.00%)	1/391 (0.26%)
Pain in extremity ^* 1	0/393 (0.00%)	1/391 (0.26%)
Pathological fracture ^* 1	2/393 (0.51%)	1/391 (0.26%)
Spinal pain ^* 1	1/393 (0.25%)	0/391 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma ^* 1	1/393 (0.25%)	0/391 (0.00%)
Colon cancer ^* 1	1/393 (0.25%)	1/391 (0.26%)
Metastases to lung ^* 1	1/393 (0.25%)	0/391 (0.00%)
Metastases to lymph nodes ^* 1	0/393 (0.00%)	1/391 (0.26%)
Metastases to meninges ^* 1	0/393 (0.00%)	1/391 (0.26%)
Metastasis ^* 1	1/393 (0.25%)	0/391 (0.00%)
Metastatic pain ^* 1	0/393 (0.00%)	1/391 (0.26%)
Metastatic renal cell carcinoma ^* 1	1/393 (0.25%)	0/391 (0.00%)
Neoplasm progression ^* 1	1/393 (0.25%)	0/391 (0.00%)
Renal cell carcinoma ^* 1	4/393 (1.02%)	1/391 (0.26%)
Tumour associated fever ^* 1	2/393 (0.51%)	0/391 (0.00%)
Tumour haemorrhage ^* 1	1/393 (0.25%)	1/391 (0.26%)
Tumour ulceration ^* 1	1/393 (0.25%)	0/391 (0.00%)
Nervous system disorders
Brain stem infarction ^* 1	0/393 (0.00%)	1/391 (0.26%)
Cerebral haemorrhage ^* 1	1/393 (0.25%)	0/391 (0.00%)
Cerebral infarction ^* 1	0/393 (0.00%)	2/391 (0.51%)
Cerebrovascular accident ^* 1	0/393 (0.00%)	3/391 (0.77%)
Dizziness ^* 1	1/393 (0.25%)	1/391 (0.26%)
Epilepsy ^* 1	1/393 (0.25%)	1/391 (0.26%)
Facial paresis ^* 1	1/393 (0.25%)	0/391 (0.00%)
Haemorrhage intracranial ^* 1	0/393 (0.00%)	1/391 (0.26%)
Haemorrhagic stroke ^* 1	0/393 (0.00%)	2/391 (0.51%)
Headache ^* 1	4/393 (1.02%)	2/391 (0.51%)
Hypertensive encephalopathy ^* 1	1/393 (0.25%)	0/391 (0.00%)
Loss of consciousness ^* 1	0/393 (0.00%)	1/391 (0.26%)
Mental impairment ^* 1	0/393 (0.00%)	1/391 (0.26%)
Somnolence ^* 1	1/393 (0.25%)	0/391 (0.00%)
Spinal cord compression ^* 1	1/393 (0.25%)	1/391 (0.26%)
Syncope ^* 1	0/393 (0.00%)	4/391 (1.02%)
Transient ischaemic attack ^* 1	0/393 (0.00%)	4/391 (1.02%)
Tremor ^* 1	0/393 (0.00%)	1/391 (0.26%)
Balance Disorder ^* 1	1/393 (0.25%)	0/391 (0.00%)
Central Nervous System Haemorrhage ^* 1	0/393 (0.00%)	1/391 (0.26%)
Seizure ^* 1	3/393 (0.76%)	1/391 (0.26%)
Toxic Encephalopathy ^* 1	0/393 (0.00%)	1/391 (0.26%)
Vascular Encephalopathy ^* 1	0/393 (0.00%)	1/391 (0.26%)
Psychiatric disorders
Confusional state ^* 1	2/393 (0.51%)	3/391 (0.77%)
Completed Suicide ^* 1	0/393 (0.00%)	1/391 (0.26%)
Depression ^* 1	0/393 (0.00%)	1/391 (0.26%)
Renal and urinary disorders
Nephrectasia ^* 1	0/393 (0.00%)	1/391 (0.26%)
Nephrolithiasis ^* 1	0/393 (0.00%)	1/391 (0.26%)
Nephrotic syndrome ^* 1	4/393 (1.02%)	2/391 (0.51%)
Proteinuria ^* 1	2/393 (0.51%)	3/391 (0.77%)
Renal disorder ^* 1	1/393 (0.25%)	0/391 (0.00%)
Renal failure ^* 1	5/393 (1.27%)	2/391 (0.51%)
Renal impairment ^* 1	1/393 (0.25%)	0/391 (0.00%)
Ureteral disorder ^* 1	0/393 (0.00%)	1/391 (0.26%)
Ureteric obstruction ^* 1	1/393 (0.25%)	0/391 (0.00%)
Ureteric stenosis ^* 1	0/393 (0.00%)	1/391 (0.26%)
Urinary retention ^* 1	1/393 (0.25%)	0/391 (0.00%)
Acute Kidney Injury ^* 1	4/393 (1.02%)	3/391 (0.77%)
Reproductive system and breast disorders
Benign prostatic hyperplasia ^* 1	1/393 (0.25%)	0/391 (0.00%)
Respiratory, thoracic and mediastinal disorders
Aspiration ^* 1	1/393 (0.25%)	0/391 (0.00%)
Atelectasis ^* 1	1/393 (0.25%)	0/391 (0.00%)
Bronchospasm ^* 1	2/393 (0.51%)	0/391 (0.00%)
Cough ^* 1	1/393 (0.25%)	1/391 (0.26%)
Dyspnoea ^* 1	3/393 (0.76%)	10/391 (2.56%)
Epistaxis ^* 1	2/393 (0.51%)	2/391 (0.51%)
Haemoptysis ^* 1	2/393 (0.51%)	3/391 (0.77%)
Hiccups ^* 1	0/393 (0.00%)	1/391 (0.26%)
Interstitial lung disease ^* 1	2/393 (0.51%)	0/391 (0.00%)
Lung disorder ^* 1	1/393 (0.25%)	0/391 (0.00%)
Nasal septum disorder ^* 1	0/393 (0.00%)	1/391 (0.26%)
Oropharyngeal pain ^* 1	1/393 (0.25%)	0/391 (0.00%)
Orthopnoea ^* 1	1/393 (0.25%)	0/391 (0.00%)
Pleural effusion ^* 1	2/393 (0.51%)	2/391 (0.51%)
Pleuritic pain ^* 1	0/393 (0.00%)	2/391 (0.51%)
Pneumonia aspiration ^* 1	0/393 (0.00%)	1/391 (0.26%)
Pneumonitis ^* 1	4/393 (1.02%)	0/391 (0.00%)
Pneumothorax ^* 1	1/393 (0.25%)	0/391 (0.00%)
Pulmonary artery thrombosis ^* 1	1/393 (0.25%)	0/391 (0.00%)
Pulmonary embolism ^* 1	5/393 (1.27%)	4/391 (1.02%)
Pulmonary hypertension ^* 1	1/393 (0.25%)	0/391 (0.00%)
Respiratory failure ^* 1	3/393 (0.76%)	1/391 (0.26%)
Sputum discoloured ^* 1	0/393 (0.00%)	1/391 (0.26%)
Skin and subcutaneous tissue disorders
Dermatitis allergic ^* 1	1/393 (0.25%)	0/391 (0.00%)
Skin haemorrhage ^* 1	1/393 (0.25%)	0/391 (0.00%)
Skin ulcer ^* 1	1/393 (0.25%)	1/391 (0.26%)
Surgical and medical procedures
Malignant tumour excision ^* 1	1/393 (0.25%)	0/391 (0.00%)
Cancer Surgery ^* 1	1/393 (0.25%)	0/391 (0.00%)
Vascular disorders
Arteriosclerosis ^* 1	0/393 (0.00%)	1/391 (0.26%)
Circulatory collapse ^* 1	1/393 (0.25%)	1/391 (0.26%)
Deep vein thrombosis ^* 1	2/393 (0.51%)	1/391 (0.26%)
Haematoma ^* 1	0/393 (0.00%)	1/391 (0.26%)
Haemorrhage ^* 1	0/393 (0.00%)	1/391 (0.26%)
Hypertension ^* 1	6/393 (1.53%)	4/391 (1.02%)
Hypertensive crisis ^* 1	1/393 (0.25%)	1/391 (0.26%)
Lymphoedema ^* 1	1/393 (0.25%)	0/391 (0.00%)
Peripheral ischaemia ^* 1	1/393 (0.25%)	0/391 (0.00%)
Thrombosis ^* 1	1/393 (0.25%)	0/391 (0.00%)
Venous thrombosis ^* 1	1/393 (0.25%)	0/391 (0.00%)
Peripheral Venous Disease ^* 1	1/393 (0.25%)	0/391 (0.00%)
* Indicates events were collected by non-systematic assessment 1 Term from vocabulary, MedDRA 18.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Bevacizumab+Temsirolimus	Bevacizumab+ Interferon-Alfa
	Affected / at Risk (%)	Affected / at Risk (%)
Total	383/393 (97.46%)	378/391 (96.68%)
Blood and lymphatic system disorders
Anaemia ^* 1	80/393 (20.36%)	66/391 (16.88%)
Leukopenia ^* 1	17/393 (4.33%)	40/391 (10.23%)
Lymphopenia ^* 1	24/393 (6.11%)	38/391 (9.72%)
Neutropenia ^* 1	18/393 (4.58%)	66/391 (16.88%)
Thrombocytopenia ^* 1	50/393 (12.72%)	40/391 (10.23%)
Ear and labyrinth disorders
Vertigo ^* 1	4/393 (1.02%)	20/391 (5.12%)
Gastrointestinal disorders
Abdominal pain ^* 1	48/393 (12.21%)	42/391 (10.74%)
Abdominal pain upper ^* 1	31/393 (7.89%)	21/391 (5.37%)
Constipation ^* 1	43/393 (10.94%)	48/391 (12.28%)
Diarrhoea ^* 1	126/393 (32.06%)	86/391 (21.99%)
Gingival bleeding ^* 1	5/393 (1.27%)	21/391 (5.37%)
Haemorrhoids ^* 1	28/393 (7.12%)	13/391 (3.32%)
Nausea ^* 1	69/393 (17.56%)	78/391 (19.95%)
Stomatitis ^* 1	102/393 (25.95%)	39/391 (9.97%)
Toothache ^* 1	37/393 (9.41%)	14/391 (3.58%)
Vomiting ^* 1	53/393 (13.49%)	53/391 (13.55%)
General disorders
Asthenia ^* 1	95/393 (24.17%)	113/391 (28.90%)
Chills ^* 1	15/393 (3.82%)	44/391 (11.25%)
Fatigue ^* 1	92/393 (23.41%)	122/391 (31.20%)
Influenza like illness ^* 1	14/393 (3.56%)	48/391 (12.28%)
Mucosal inflammation ^* 1	105/393 (26.72%)	40/391 (10.23%)
Oedema peripheral ^* 1	67/393 (17.05%)	32/391 (8.18%)
Pyrexia ^* 1	79/393 (20.10%)	154/391 (39.39%)
Infections and infestations
Upper respiratory tract infection ^* 1	20/393 (5.09%)	15/391 (3.84%)
Urinary tract infection ^* 1	23/393 (5.85%)	21/391 (5.37%)
Investigations
Alanine aminotransferase increased ^* 1	38/393 (9.67%)	35/391 (8.95%)
Aspartate aminotransferase increased ^* 1	33/393 (8.40%)	41/391 (10.49%)
Blood creatinine increased ^* 1	40/393 (10.18%)	25/391 (6.39%)
Weight decreased ^* 1	90/393 (22.90%)	93/391 (23.79%)
Blood Alkaline Phosphatase Increased ^* 1	20/393 (5.09%)	14/391 (3.58%)
Metabolism and nutrition disorders
Decreased appetite ^* 1	103/393 (26.21%)	127/391 (32.48%)
Hypercholesterolaemia ^* 1	126/393 (32.06%)	39/391 (9.97%)
Hyperglycaemia ^* 1	86/393 (21.88%)	19/391 (4.86%)
Hyperkalaemia ^* 1	29/393 (7.38%)	37/391 (9.46%)
Hypertriglyceridaemia ^* 1	114/393 (29.01%)	82/391 (20.97%)
Hypocalcaemia ^* 1	24/393 (6.11%)	13/391 (3.32%)
Hypomagnesaemia ^* 1	20/393 (5.09%)	16/391 (4.09%)
Hyponatraemia ^* 1	23/393 (5.85%)	21/391 (5.37%)
Hypophosphataemia ^* 1	40/393 (10.18%)	18/391 (4.60%)
Hypokalaemia ^* 1	20/393 (5.09%)	4/391 (1.02%)
Musculoskeletal and connective tissue disorders
Arthralgia ^* 1	52/393 (13.23%)	49/391 (12.53%)
Back pain ^* 1	47/393 (11.96%)	53/391 (13.55%)
Bone pain ^* 1	18/393 (4.58%)	22/391 (5.63%)
Musculoskeletal chest pain ^* 1	27/393 (6.87%)	19/391 (4.86%)
Musculoskeletal pain ^* 1	14/393 (3.56%)	28/391 (7.16%)
Myalgia ^* 1	19/393 (4.83%)	60/391 (15.35%)
Pain in extremity ^* 1	43/393 (10.94%)	35/391 (8.95%)
Nervous system disorders
Dizziness ^* 1	29/393 (7.38%)	37/391 (9.46%)
Dysgeusia ^* 1	33/393 (8.40%)	21/391 (5.37%)
Headache ^* 1	77/393 (19.59%)	82/391 (20.97%)
Psychiatric disorders
Anxiety ^* 1	7/393 (1.78%)	21/391 (5.37%)
Depression ^* 1	11/393 (2.80%)	22/391 (5.63%)
Insomnia ^* 1	28/393 (7.12%)	31/391 (7.93%)
Renal and urinary disorders
Proteinuria ^* 1	143/393 (36.39%)	111/391 (28.39%)
Respiratory, thoracic and mediastinal disorders
Cough ^* 1	79/393 (20.10%)	70/391 (17.90%)
Dysphonia ^* 1	13/393 (3.31%)	30/391 (7.67%)
Dyspnoea ^* 1	36/393 (9.16%)	49/391 (12.53%)
Epistaxis ^* 1	110/393 (27.99%)	82/391 (20.97%)
Oropharyngeal pain ^* 1	28/393 (7.12%)	16/391 (4.09%)
Skin and subcutaneous tissue disorders
Dry skin ^* 1	27/393 (6.87%)	13/391 (3.32%)
Pruritus ^* 1	60/393 (15.27%)	26/391 (6.65%)
Rash ^* 1	126/393 (32.06%)	32/391 (8.18%)
Vascular disorders
Hypertension ^* 1	128/393 (32.57%)	102/391 (26.09%)
* Indicates events were collected by non-systematic assessment 1 Term from vocabulary, MedDRA 18.0

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.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Pfizer ClinicalTrials.gov Call Center
Organization:	Pfizer, Inc.
Phone:	1-800-718-1021
EMail:	ClinicalTrials.gov_Inquiries@pfizer.com

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

de Velasco G, McKay RR, Lin X, Moreira RB, Simantov R, Choueiri TK. Comprehensive Analysis of Survival Outcomes in Non-Clear Cell Renal Cell Carcinoma Patients Treated in Clinical Trials. Clin Genitourin Cancer. 2017 Dec;15(6):652-660.e1. doi: 10.1016/j.clgc.2017.03.004. Epub 2017 Mar 21.

Grünwald V, Lin X, Kalanovic D, Simantov R. Early Tumour Shrinkage: A Tool for the Detection of Early Clinical Activity in Metastatic Renal Cell Carcinoma. Eur Urol. 2016 Dec;70(6):1006-1015. doi: 10.1016/j.eururo.2016.05.010. Epub 2016 May 26.

Rini BI, Bellmunt J, Clancy J, Wang K, Niethammer AG, Hariharan S, Escudier B. Randomized phase III trial of temsirolimus and bevacizumab versus interferon alfa and bevacizumab in metastatic renal cell carcinoma: INTORACT trial. J Clin Oncol. 2014 Mar 10;32(8):752-9. doi: 10.1200/JCO.2013.50.5305. Epub 2013 Dec 2.

Layout table for additonal information

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT00631371
Other Study ID Numbers:	3066K1-3311 B1771006 ( Other Identifier: Alias Study Number ) 2007-003793-26 ( EudraCT Number )
First Submitted:	February 28, 2008
First Posted:	March 7, 2008
Results First Submitted:	April 18, 2013
Results First Posted:	June 4, 2013
Last Update Posted:	April 27, 2016

To Top