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ARCC: Study Evaluating Interferon And CCI-779 In Advanced Renal Cell Carcinoma

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00065468
Collaborator
(none)
626
Enrollment
154
Locations
3
Arms
92
Duration (Months)
4.1
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is efficacy. The primary efficacy endpoint of this study is a comparison of the overall survival of subjects treated with CCI-779 [Temsirolimus], administered intravenously [IV] once weekly and the combination of CCI-779, administered IV once weekly with Interferon Alfa [IFN alfa] subcutaneously [SC] three times per week [TIW], compared with the overall survival of subjects treated with IFN alfa (SC TIW) alone, in poor-prognosis subjects with advanced RCC.

Condition or Disease Intervention/Treatment Phase
  • Drug: Interferon Alfa
  • Drug: CCI-779
  • Drug: Interferon Alfa and CCI-779
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
626 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Three-Arm, Randomized, Open-Label Study Of Interferon Alfa Alone, CCI-779 Alone, And The Combination Of Interferon Alfa And CCI-779 In First-Line Poor-Prognosis Subjects With Advanced Renal Cell Carcinoma.
Study Start Date :
Jul 1, 2003
Actual Primary Completion Date :
Jun 1, 2006
Actual Study Completion Date :
Mar 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: A

Drug: Interferon Alfa
Interferon alfa (Roferon) 3 MU given Sub Cutaneously three time /week for the first week, 9 MU given Sub Cutaneously three time /week for the second week, 18 MU given Sub Cutaneously three time /week thereafter.
Experimental: B

Drug: CCI-779
25 mg of CCI-779 given Intra Venously once per week
Experimental: C

Drug: Interferon Alfa and CCI-779
15 mg of CCI-779 given Intra Venously once per week; 6 MU of IFN alfa (Roferon) given Sub Cutaneously three time /week

Outcome Measures

Primary Outcome Measures

  1. Overall Survival (OS) [Baseline up to Month 80]

    Overall survival is the duration from randomization to death. For participants who are alive, overall survival is censored at the last contact.

Secondary Outcome Measures

  1. Progression-Free Survival (PFS) [Baseline, monthly until tumor progression or death (up to Month 80)]

    PFS based on Independent Central Review Assessment. The period from randomization until disease progression, death or date of last contact.

  2. Percentage of Participants With Objective Response [Baseline, every 2 months until tumor progression or death (up to Month 80)]

    Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was the disappearance of all target lesions and non target lesions. PR was at least a 30 percent (%) decrease in sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

  3. Percentage of Participants With Clinical Benefit [Baseline, every 2 months until tumor progression or death (up to Month 80)]

    Clinical benefit: confirmed CR or PR or had stable disease (SD) lasting at least 24 weeks. CR was the disappearance of all target lesions and non target lesions. PR was at least a 30% decrease in sum of the LD of target lesions, taking as reference the baseline sum LD. SD was having neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

  4. Duration of Response (DR) [Baseline, every month until tumor progression or death (up to Month 80)]

    DR: Time from first documentation of objective tumor response to first date that recurrence or progressive disease (PD) was objectively documented, taking as a reference for PD, the smallest sum LD recorded since randomization.

  5. Time to Treatment Failure (TTF) [Baseline, every month until tumor progression or death (up to Month 80)]

    TTF is defined as the time from the date of randomization to the date of PD or death, withdrawal from treatment due to an adverse event (AE), withdrawal of voluntary consent, or lost to follow-up, whichever occurred first, censored at the date of the conclusion of treatment phase.

  6. Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST) [Baseline to Month 80]

    The Q-Twist is not a score calculated for each participant but is defined only on a by treatment group basis. For each treatment group, it is the weighted sum of the mean durations of the health states Tox, Twist, and Relapse. Tox is defined as time with severe toxicity related to treatment; Twist: time without symptoms or toxic side effects; and Relapse: time after relapse/progression. The mean duration of each health state is calculated based on the area under the Kaplan Meier curve pertaining to that health state. There is no direct method for calculating the "dispersion" of Q-Twist, and it is typically done using bootstrap method for purposes of inference (see, e.g., Glasziou PP, Simes RJ, Gelber RD. Quality adjusted survival analysis. Stat Med 1990; 9: 1259-76). In practice, as apparently in the case with this study, the intermediate values resulting from the bootstrap exercise were not displayed.

  7. European Quality of Life Health Questionnaire (EQ-5D) - Index Score [Baseline]

    EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. EQ-5D index measured 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Range of EQ-5D index score = -0.594 to 1 where higher scores indicated a better health state.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • This study will be conducted in subjects with histologically confirmed, advanced (stage IV or recurrent disease) RCC who have not received prior systemic therapy for their disease,
Exclusion Criteria:

  • Subjects with central nervous system (CNS) metastases

  • Prior anticancer therapy for RCC

  • Prior investigational therapy/agents within 4 weeks of randomization

Contacts and Locations

Locations

Site City State Country Postal Code
1 Pfizer Investigational Site Little Rock Arkansas United States 72205
2 Pfizer Investigational Site La Verne California United States 91750
3 Pfizer Investigational Site Los Angeles California United States 90024-2828
4 Pfizer Investigational Site San Diego California United States 92123
5 Pfizer Investigational Site San Francisco California United States 94115
6 Pfizer Investigational Site Waterbury Connecticut United States 06708
7 Pfizer Investigational Site Boca Raton Florida United States 33428
8 Pfizer Investigational Site Miami Florida United States 33136
9 Pfizer Investigational Site Chicago Illinois United States 60612-3824
10 Pfizer Investigational Site Urbana Illinois United States 61801
11 Pfizer Investigational Site Indianapolis Indiana United States 46303
12 Pfizer Investigational Site South Bend Indiana United States 46601
13 Pfizer Investigational Site Terre Haute Indiana United States 47802
14 Pfizer Investigational Site Kansas City Kansas United States 66160-7136
15 Pfizer Investigational Site Louisville Kentucky United States 40202
16 Pfizer Investigational Site New Orleans Louisiana United States 70121
17 Pfizer Investigational Site Baltimore Maryland United States 21231-1000
18 Pfizer Investigational Site Boston Massachusetts United States 02215
19 Pfizer Investigational Site Ann Arbor Michigan United States 48109-0942
20 Pfizer Investigational Site Detroit Michigan United States 48202
21 Pfizer Investigational Site Kansas City Missouri United States 64131
22 Pfizer Investigational Site St. Louis Missouri United States 63110
23 Pfizer Investigational Site Billings Montana United States 59101
24 Pfizer Investigational Site Great Falls Montana United States 59405
25 Pfizer Investigational Site Lebanon New Hampshire United States 03766
26 Pfizer Investigational Site East Orange New Jersey United States 07018
27 Pfizer Investigational Site Morristown New Jersey United States 07960
28 Pfizer Investigational Site Bronx New York United States 10466
29 Pfizer Investigational Site New York New York United States 10021
30 Pfizer Investigational Site Rochester New York United States 14642
31 Pfizer Investigational Site Valhalla New York United States 10595
32 Pfizer Investigational Site Durham North Carolina United States 27710
33 Pfizer Investigational Site Hickory North Carolina United States 28602
34 Pfizer Investigational Site Cleveland Ohio United States 44195
35 Pfizer Investigational Site Oklahoma City Oklahoma United States 73104
36 Pfizer Investigational Site Portland Oregon United States 97213-2933
37 Pfizer Investigational Site Hershey Pennsylvania United States 17033-0850
38 Pfizer Investigational Site Philadelphia Pennsylvania United States 19111
39 Pfizer Investigational Site Pittsburgh Pennsylvania United States 15213
40 Pfizer Investigational Site Charleston South Carolina United States 29414
41 Pfizer Investigational Site Knoxville Tennessee United States 37920
42 Pfizer Investigational Site Memphis Tennessee United States 38120
43 Pfizer Investigational Site Nashville Tennessee United States 37232-6310
44 Pfizer Investigational Site Houston Texas United States 77030
45 Pfizer Investigational Site Salt Lake City Utah United States 84112
46 Pfizer Investigational Site Richmond Virginia United States 23249
47 Pfizer Investigational Site Seattle Washington United States 98101
48 Pfizer Investigational Site Seattle Washington United States 98109-1023
49 Pfizer Investigational Site Buenos Aires Argentina
50 Pfizer Investigational Site San Miguel de Tucuman Tucuman Argentina 4000
51 Pfizer Investigational Site Buenos Aires Argentina C1426ANZ
52 Pfizer Investigational Site Cordoba Argentina 5000
53 Pfizer Investigational Site Mendoza Argentina
54 Pfizer Investigational Site Quilmes Argentina
55 Pfizer Investigational Site Kogarah New South Wales Australia 2217
56 Pfizer Investigational Site Newcastle New South Wales Australia
57 Pfizer Investigational Site Westmead New South Wales Australia 2145
58 Pfizer Investigational Site Adelaide South Australia Australia 5000
59 Pfizer Investigational Site Footscray Victoria Australia 3012
60 Pfizer Investigational Site Heidelberg Victoria Australia 3084
61 Pfizer Investigational Site Melbourne Victoria Australia 3050
62 Pfizer Investigational Site Edmonton Alberta Canada T6G 1Z2
63 Pfizer Investigational Site Kelowna British Columbia Canada V1Y 5L3
64 Pfizer Investigational Site Vancouver British Columbia Canada V5Z 3J5
65 Pfizer Investigational Site Winnipeg Manitoba Canada R3E 0C9
66 Pfizer Investigational Site Halifax Nova Scotia Canada B3H 1V7
67 Pfizer Investigational Site London Ontario Canada N6A 4L5
68 Pfizer Investigational Site Newmarket Ontario Canada L3Y 2P9
69 Pfizer Investigational Site Ottawa Ontario Canada K1H 8L6
70 Pfizer Investigational Site Toronto Ontario Canada M4N 3M5
71 Pfizer Investigational Site Greenfield Park Quebec Canada J4V 2H1
72 Pfizer Investigational Site Montreal Quebec Canada H2L 4M1
73 Pfizer Investigational Site Montreal Quebec Canada H2X 3J4
74 Pfizer Investigational Site Montreal Quebec Canada H3T 1E2
75 Pfizer Investigational Site Quebec City Quebec Canada G1R 2J6
76 Pfizer Investigational Site Sherbrooke Quebec Canada J1H 5N4
77 Pfizer Investigational Site Hamilton, Ontario Canada L8N 4A6
78 Pfizer Investigational Site Brno Czech Republic 656 53
79 Pfizer Investigational Site Prague 5 Czech Republic 150 00
80 Pfizer Investigational Site Sremska Kamenica Novi Sad Former Serbia and Montenegro 21204
81 Pfizer Investigational Site Bonn NRW Germany 53105
82 Pfizer Investigational Site Essen NRW Germany 45122
83 Pfizer Investigational Site Mainz RP Germany D-55101
84 Pfizer Investigational Site Heraklion Creete Greece
85 Pfizer Investigational Site Patra Greece
86 Pfizer Investigational Site Budapest Hungary H-1122
87 Pfizer Investigational Site Roma RM Italy 00144
88 Pfizer Investigational Site Foggia Italy 71100
89 Pfizer Investigational Site Milano Italy 20132
90 Pfizer Investigational Site Daugavpils Latvia
91 Pfizer Investigational Site Riga Latvia 1002
92 Pfizer Investigational Site Riga Latvia 1079
93 Pfizer Investigational Site Vilnius Lithuania 2021
94 Pfizer Investigational Site Monterrey Nuevo Leon Mexico 64000
95 Pfizer Investigational Site Leon Guanajuato Mexico 37000
96 Pfizer Investigational Site Nijmegen GA Netherlands 6525
97 Pfizer Investigational Site Amsterdam Netherlands 1105 AZ
98 Pfizer Investigational Site Enschede Netherlands 7511 JX
99 Pfizer Investigational Site Bytom Poland 41-902
100 Pfizer Investigational Site Lodz Poland 93-509
101 Pfizer Investigational Site Lublin Poland 20-090
102 Pfizer Investigational Site Olsztyn Poland 10-228
103 Pfizer Investigational Site Opole Poland 45-060
104 Pfizer Investigational Site Poznan Poland 61-878
105 Pfizer Investigational Site Siedlce Poland 08-110
106 Pfizer Investigational Site Warszawa Poland 00-909
107 Pfizer Investigational Site Warszawa Poland 02-781
108 Pfizer Investigational Site Barnaul Russian Federation 656052
109 Pfizer Investigational Site Kemerovo Russian Federation 650003
110 Pfizer Investigational Site Moscow Russian Federation 115478
111 Pfizer Investigational Site Moscow Russian Federation 121356
112 Pfizer Investigational Site Moscow Russian Federation 125284
113 Pfizer Investigational Site Moscow Russian Federation 143423
114 Pfizer Investigational Site Obninsk Russian Federation 249036
115 Pfizer Investigational Site Saint Petersburg Russian Federation 188663
116 Pfizer Investigational Site Saint Petersburg Russian Federation 194354
117 Pfizer Investigational Site Saint Petersburg Russian Federation 197758
118 Pfizer Investigational Site Saint Petersburg Russian Federation
119 Pfizer Investigational Site St Petersburg Russian Federation 197758
120 Pfizer Investigational Site Ufa Russian Federation 450005
121 Pfizer Investigational Site Ufa Russian Federation
122 Pfizer Investigational Site Belgrade Serbia 11000
123 Pfizer Investigational Site Banska Bystrica Slovakia 974 01
124 Pfizer Investigational Site Bratislava Slovakia 833 10
125 Pfizer Investigational Site Martin Slovakia 03659
126 Pfizer Investigational Site Zlina Slovakia 012 07
127 Pfizer Investigational Site Port Elizabeth Eastern Cape South Africa 6006
128 Pfizer Investigational Site Johannesburg Gauteng South Africa 2197
129 Pfizer Investigational Site Cape Town South Africa 7505
130 Pfizer Investigational Site Gauteng South Africa
131 Pfizer Investigational Site Oviedo Asturias Spain 33006
132 Pfizer Investigational Site Badalona Barcelona Spain 08916
133 Pfizer Investigational Site Barcelona Spain 08025
134 Pfizer Investigational Site Madrid Spain 28040
135 Pfizer Investigational Site Göteborg Sweden 41345
136 Pfizer Investigational Site Stockholm Sweden 171 76
137 Pfizer Investigational Site Uppsala Sweden 751 85
138 Pfizer Investigational Site Taipei ROC Taiwan 112
139 Pfizer Investigational Site Taichung Taiwan
140 Pfizer Investigational Site Taipei Taiwan 104
141 Pfizer Investigational Site Taoyuan Taiwan 333
142 Pfizer Investigational Site Istanbul Turkey
143 Pfizer Investigational Site Izmir Turkey 35100
144 Pfizer Investigational Site Dnietropetrovsk Ukraine
145 Pfizer Investigational Site Donetsk Ukraine 83 092
146 Pfizer Investigational Site Kharkov Ukraine 61 037
147 Pfizer Investigational Site Kiev Ukraine 03 142
148 Pfizer Investigational Site Lviv Ukraine 79031
149 Pfizer Investigational Site Zaporozhye Ukraine 69103
150 Pfizer Investigational Site Manchester Lancashire United Kingdom M20 4BX
151 Pfizer Investigational Site Glasgow Strathclyde United Kingdom G11 6NT
152 Pfizer Investigational Site Sutton Surrey United Kingdom SM2 5PT
153 Pfizer Investigational Site Nottingham United Kingdom NG5 1PB
154 Pfizer Investigational Site

Sponsors and Collaborators

  • Pfizer

Investigators

  • Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00065468
Other Study ID Numbers:
  • 3066K1-304
  • NCT00070330
First Posted:
Jul 25, 2003
Last Update Posted:
Oct 25, 2012
Last Verified:
Sep 1, 2012
Keywords provided by Pfizer
Advanced Renal Cell Carcinoma
Kidney Cancer
Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Kidney Neoplasms
Interferons
Interferon-alpha
Sirolimus

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Interferon Alfa Temsirolimus Interferon Alfa and Temsirolimus
Arm/Group Description Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
Period Title: Overall Study
STARTED 207 209 210
Received Treatment 200 208 208
COMPLETED 0 0 0
NOT COMPLETED 207 209 210

Baseline Characteristics

Arm/Group Title Interferon Alfa Temsirolimus Interferon Alfa and Temsirolimus Total
Arm/Group Description Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal Total of all reporting groups
Overall Participants 207 209 210 626
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
59.2
(10.4)
58.7
(10.0)
59.3
(9.8)
59.1
(10.1)
Sex: Female, Male (Count of Participants)
Female
59
28.5%
70
33.5%
65
31%
194
31%
Male
148
71.5%
139
66.5%
145
69%
432
69%

Outcome Measures

1. Primary Outcome
Title Overall Survival (OS)
Description Overall survival is the duration from randomization to death. For participants who are alive, overall survival is censored at the last contact.
Time Frame Baseline up to Month 80

Outcome Measure Data

Analysis Population Description
Intent-to-treat (ITT) Population: all randomized participants
Arm/Group Title Interferon Alfa Temsirolimus Interferon Alfa and Temsirolimus
Arm/Group Description Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
Measure Participants 207 209 210
Median (95% Confidence Interval) [months]
7.3
10.9
8.4
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Alfa, Temsirolimus
Comments
Type of Statistical Test Non-Inferiority or Equivalence
Comments 2 null hypotheses (Ho) were tested: 1) Survival distributions for temsirolimus alone and Interferon Alfa (IFN)-alone treatment groups were identical. 2) Survival distributions for temsirolimus in combination with IFN and IFN-alone treatment groups were identical. The alternative hypothesis (Ha) for each test was that the survival distributions differed.
Statistical Test of Hypothesis p-Value 0.0252
Comments
Method Log Rank
Comments Stratified by prior nephrectomy and region
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.63 to 0.97
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Alfa, Interferon Alfa and Temsirolimus
Comments
Type of Statistical Test Non-Inferiority or Equivalence
Comments 2 null hypotheses (Ho) were tested: 1) Survival distributions for temsirolimus alone and IFN-alone treatment groups were identical. 2) Survival distributions for temsirolimus in combination with IFN and IFN-alone treatment groups were identical. The alternative hypothesis (Ha) for each test was that the survival distributions differed.
Statistical Test of Hypothesis p-Value 0.4902
Comments
Method Log Rank
Comments Stratified by prior nephrectomy and region
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.75 to 1.15
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
Title Progression-Free Survival (PFS)
Description PFS based on Independent Central Review Assessment. The period from randomization until disease progression, death or date of last contact.
Time Frame Baseline, monthly until tumor progression or death (up to Month 80)

Outcome Measure Data

Analysis Population Description
ITT
Arm/Group Title Interferon Alfa Temsirolimus Interferon Alfa and Temsirolimus
Arm/Group Description Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
Measure Participants 207 209 210
Median (95% Confidence Interval) [months]
3.2
5.6
4.9
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Alfa, Temsirolimus
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0042
Comments
Method Log Rank
Comments Stratified by prior nephrectomy and region
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.60 to 0.91
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Alfa, Interferon Alfa and Temsirolimus
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0107
Comments
Method Log Rank
Comments Stratified by prior nephrectomy and region
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
0.62 to 0.94
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
Title Percentage of Participants With Objective Response
Description Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was the disappearance of all target lesions and non target lesions. PR was at least a 30 percent (%) decrease in sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Time Frame Baseline, every 2 months until tumor progression or death (up to Month 80)

Outcome Measure Data

Analysis Population Description
ITT
Arm/Group Title Interferon Alfa Temsirolimus Interferon Alfa and Temsirolimus
Arm/Group Description Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
Measure Participants 207 209 210
Number (95% Confidence Interval) [percentage of participants]
5.3
2.6%
9.1
4.4%
9.5
4.5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Alfa, Temsirolimus
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1361
Comments
Method Cochran-Mantel-Haenszel
Comments Stratified by prior nephrectomy and region
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Alfa, Interferon Alfa and Temsirolimus
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1062
Comments
Method Cochran-Mantel-Haenszel
Comments Stratified by prior nephrectomy and region
4. Secondary Outcome
Title Percentage of Participants With Clinical Benefit
Description Clinical benefit: confirmed CR or PR or had stable disease (SD) lasting at least 24 weeks. CR was the disappearance of all target lesions and non target lesions. PR was at least a 30% decrease in sum of the LD of target lesions, taking as reference the baseline sum LD. SD was having neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time Frame Baseline, every 2 months until tumor progression or death (up to Month 80)

Outcome Measure Data

Analysis Population Description
ITT
Arm/Group Title Interferon Alfa Temsirolimus Interferon Alfa and Temsirolimus
Arm/Group Description Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
Measure Participants 207 209 210
Number (95% Confidence Interval) [percentage of participants]
16.4
7.9%
34.0
16.3%
30.0
14.3%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Alfa, Temsirolimus
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Cochran-Mantel-Haenszel
Comments Stratified by prior nephrectomy and region
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Alfa, Interferon Alfa and Temsirolimus
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0011
Comments
Method Cochran-Mantel-Haenszel
Comments Stratified by prior nephrectomy and region
5. Secondary Outcome
Title Duration of Response (DR)
Description DR: Time from first documentation of objective tumor response to first date that recurrence or progressive disease (PD) was objectively documented, taking as a reference for PD, the smallest sum LD recorded since randomization.
Time Frame Baseline, every month until tumor progression or death (up to Month 80)

Outcome Measure Data

Analysis Population Description
ITT subset of participants who had a response
Arm/Group Title Interferon Alfa Temsirolimus Interferon Alfa and Temsirolimus
Arm/Group Description Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
Measure Participants 11 19 20
Median (95% Confidence Interval) [months]
7.4
11.1
9.3
6. Secondary Outcome
Title Time to Treatment Failure (TTF)
Description TTF is defined as the time from the date of randomization to the date of PD or death, withdrawal from treatment due to an adverse event (AE), withdrawal of voluntary consent, or lost to follow-up, whichever occurred first, censored at the date of the conclusion of treatment phase.
Time Frame Baseline, every month until tumor progression or death (up to Month 80)

Outcome Measure Data

Analysis Population Description
ITT
Arm/Group Title Interferon Alfa Temsirolimus Interferon Alfa and Temsirolimus
Arm/Group Description Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
Measure Participants 207 209 210
Median (95% Confidence Interval) [months]
1.9
3.7
2.5
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Alfa, Temsirolimus
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method Log Rank
Comments Stratified by prior nephrectomy and region
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.51 to 0.76
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Alfa, Interferon Alfa and Temsirolimus
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0020
Comments
Method Log Rank
Comments Stratified by prior nephrectomy and region
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.60 to 0.89
Parameter Dispersion Type:
Value:
Estimation Comments
7. Secondary Outcome
Title Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST)
Description The Q-Twist is not a score calculated for each participant but is defined only on a by treatment group basis. For each treatment group, it is the weighted sum of the mean durations of the health states Tox, Twist, and Relapse. Tox is defined as time with severe toxicity related to treatment; Twist: time without symptoms or toxic side effects; and Relapse: time after relapse/progression. The mean duration of each health state is calculated based on the area under the Kaplan Meier curve pertaining to that health state. There is no direct method for calculating the "dispersion" of Q-Twist, and it is typically done using bootstrap method for purposes of inference (see, e.g., Glasziou PP, Simes RJ, Gelber RD. Quality adjusted survival analysis. Stat Med 1990; 9: 1259-76). In practice, as apparently in the case with this study, the intermediate values resulting from the bootstrap exercise were not displayed.
Time Frame Baseline to Month 80

Outcome Measure Data

Analysis Population Description
ITT
Arm/Group Title Interferon Alfa Temsirolimus Interferon Alfa and Temsirolimus
Arm/Group Description Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
Measure Participants 207 209 210
Number [months]
6.9083
8.3707
7.4821
8. Secondary Outcome
Title European Quality of Life Health Questionnaire (EQ-5D) - Index Score
Description EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. EQ-5D index measured 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Range of EQ-5D index score = -0.594 to 1 where higher scores indicated a better health state.
Time Frame Baseline

Outcome Measure Data

Analysis Population Description
ITT;(N)=participants with evaluable data. Week 12 and 32 data collected for individual participants but not summarized.
Arm/Group Title Interferon Alfa Temsirolimus Interferon Alfa and Temsirolimus
Arm/Group Description Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
Measure Participants 197 204 197
Median (Full Range) [units on a scale]
0.656
0.689
0.689

Adverse Events

Time Frame
Adverse Event Reporting Description The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.
Arm/Group Title Interferon Alfa Temsirolimus Interferon Alfa and Temsirolimus
Arm/Group Description Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal
All Cause Mortality
Interferon Alfa Temsirolimus Interferon Alfa and Temsirolimus
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN)
Serious Adverse Events
Interferon Alfa Temsirolimus Interferon Alfa and Temsirolimus
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 99/200 (49.5%) 82/208 (39.4%) 122/208 (58.7%)
Blood and lymphatic system disorders
ANEMIA 12/200 (6%) 11/208 (5.3%) 20/208 (9.6%)
THROMBOCYTOPENIA 0/200 (0%) 1/208 (0.5%) 4/208 (1.9%)
ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
DISSEMINATED INTRAVASCULAR COAGULATION 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
FIBRINOGEN INCREASED 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
THROMBIN TIME PROLONGED 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
Cardiac disorders
ATRIAL FIBRILLATION 2/200 (1%) 2/208 (1%) 1/208 (0.5%)
CONGESTIVE HEART FAILURE 1/200 (0.5%) 2/208 (1%) 0/208 (0%)
DEEP VEIN THROMBOSIS 1/200 (0.5%) 2/208 (1%) 0/208 (0%)
HYPERTENSION 1/200 (0.5%) 2/208 (1%) 2/208 (1%)
MYOCARDIAL INFARCT 2/200 (1%) 2/208 (1%) 1/208 (0.5%)
PULMONARY EMBOLUS 1/200 (0.5%) 2/208 (1%) 3/208 (1.4%)
CEREBROVASCULAR ACCIDENT 0/200 (0%) 1/208 (0.5%) 1/208 (0.5%)
HEART FAILURE 1/200 (0.5%) 1/208 (0.5%) 2/208 (1%)
INTRACRANIAL HEMORRHAGE 0 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
PERICARDIAL EFFUSION 1/200 (0.5%) 1/208 (0.5%) 0/208 (0%)
PERIPHERAL GANGRENE 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
SYNCOPE 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
TACHYCARDIA SINUS 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
ANGINA PECTORIS 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
CARDIOMYOPATHY 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
CEREBRAL HEMORRHAGE 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
CEREBRAL ISCHEMIA 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
CEREBROVASCULAR DISORDER 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
HEART ARREST 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
HEMORRHAGE 1/200 (0.5%) 0/208 (0%) 2/208 (1%)
HYPOTENSION 2/200 (1%) 0/208 (0%) 2/208 (1%)
HYPOVOLEMIA 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
POSTURAL HYPOTENSION 1 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
SHOCK 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
THROMBOSIS 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
VASCULAR DISORDER 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
Endocrine disorders
DIABETES MELLITUS 0/200 (0%) 2/208 (1%) 0/208 (0%)
THYROID CARCINOMA 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
Eye disorders
CATARACT SPECIFIED 0/200 (0%) 0/208 (0%) 2/208 (1%)
DIPLOPIA 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
Gastrointestinal disorders
STOMATITIS 0/200 (0%) 3/208 (1.4%) 4/208 (1.9%)
GASTROINTESTINAL HEMORRHAGE 0/200 (0%) 2/208 (1%) 0/208 (0%)
NAUSEA 3/200 (1.5%) 2/208 (1%) 2/208 (1%)
VOMITING 3/200 (1.5%) 2/208 (1%) 1/208 (0.5%)
DIARRHEA 1/200 (0.5%) 1/208 (0.5%) 6/208 (2.9%)
GASTROINTESTINAL DISORDER 1/200 (0.5%) 1/208 (0.5%) 0/208 (0%)
ILEUS 0/200 (0%) 1/208 (0.5%) 1/208 (0.5%)
INTESTINAL PERFORATION 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
MUCOSITIS 0/200 (0%) 1/208 (0.5%) 2/208 (1%)
ANOREXIA 1/200 (0.5%) 0/208 (0%) 3/208 (1.4%)
COLITIS 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
CONSTIPATION 1/200 (0.5%) 0/208 (0%) 1/208 (0.5%)
GASTROENTERITIS 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
HEMATEMESIS 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
HEMORRHAGIC GASTRITIS 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
HEPATIC FAILURE 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
HEPATITIS 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
INTESTINAL OBSTRUCTION 1/200 (0.5%) 0/208 (0%) 1/208 (0.5%)
LIVER FATTY DEPOSIT 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
MELENA 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
PROCTITIS 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
RECTAL HEMORRHAGE 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
General disorders
ABDOMINAL PAIN 1/200 (0.5%) 5/208 (2.4%) 4/208 (1.9%)
BACK PAIN 2/200 (1%) 4/208 (1.9%) 1/208 (0.5%)
CARCINOMA 9/200 (4.5%) 4/208 (1.9%) 13/208 (6.3%)
ASTHENIA 7/200 (3.5%) 3/208 (1.4%) 10/208 (4.8%)
FEVER 3/200 (1.5%) 3/208 (1.4%) 8/208 (3.8%)
ASCITES 1/200 (0.5%) 2/208 (1%) 0/208 (0%)
GENERAL PHYSICAL HEALTH DETERIORATION 0/200 (0%) 2/208 (1%) 1/208 (0.5%)
PAIN 0/200 (0%) 2/208 (1%) 3/208 (1.4%)
ABSCESS 1/200 (0.5%) 1/208 (0.5%) 0/208 (0%)
ACCIDENTAL INJURY 0/200 (0%) 1/208 (0.5%) 3/208 (1.4%)
CHEST PAIN 1/200 (0.5%) 1/208 (0.5%) 1/208 (0.5%)
HERNIA 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
INFECTION 1/200 (0.5%) 1/208 (0.5%) 1/208 (0.5%)
INFLAMMATION 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
MALAISE 1/200 (0.5%) 1/208 (0.5%) 0/208 (0%)
MEDICATION ERROR 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
NEOPLASM 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
OVERDOSE 0/200 (0%) 1/208 (0.5%) 2/208 (1%)
PELVIC PAIN 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
SEPSIS 0/200 (0%) 1/208 (0.5%) 3/208 (1.4%)
ABDOMINAL SYNDROME ACUTE 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
ACCIDENTAL OVERDOSE 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
ALLERGIC REACTION 1/200 (0.5%) 0/208 (0%) 1/208 (0.5%)
CELLULITIS 1/200 (0.5%) 0/208 (0%) 3/208 (1.4%)
CHILLS 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
FLU SYNDROME 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
GENERALIZED EDEMA 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
NECK PAIN 0/200 (0%) 0/208 (0%) 2/208 (1%)
TUMOR LYSIS SYNDROME 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
DEVICE MALFUNCTION 0/200 (0%) 0/208 (0%) 2/208 (1%)
Metabolism and nutrition disorders
HYPERGLYCEMIA 0/200 (0%) 6/208 (2.9%) 0/208 (0%)
DEHYDRATION 7/200 (3.5%) 5/208 (2.4%) 10/208 (4.8%)
CREATININE INCREASED 0/200 (0%) 3/208 (1.4%) 1/208 (0.5%)
HYPERCALCEMIA 2/200 (1%) 3/208 (1.4%) 4/208 (1.9%)
HYPERKALEMIA 2/200 (1%) 2/208 (1%) 2/208 (1%)
ALKALINE PHOSPHATASE INCREASED 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
BUN INCREASED 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
HYPERLIPEMIA 0/200 (0%) 1/208 (0.5%) 3/208 (1.4%)
HYPOCALCEMIA 0/200 (0%) 1/208 (0.5%) 2/208 (1%)
HYPOKALEMIA 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
HYPONATREMIA 0/200 (0%) 1/208 (0.5%) 1/208 (0.5%)
PERIPHERAL EDEMA 1/200 (0.5%) 1/208 (0.5%) 1/208 (0.5%)
SGOT INCREASED 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
BILIRUBINEMIA 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
CACHEXIA 0/200 (0%) 0/208 (0%) 2/208 (1%)
FAILURE TO THRIVE 1/200 (0.5%) 0/208 (0%) 1/208 (0.5%)
HYPOGLYCEMIAHYPOGLYCEMIA 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
HYPOPROTEINEMIA 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
KETOSIS 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
WEIGHT LOSS 1/200 (0.5%) 0/208 (0%) 1/208 (0.5%)
Musculoskeletal and connective tissue disorders
PATHOLOGICAL FRACTURE 0/200 (0%) 2/208 (1%) 1/208 (0.5%)
BONE PAIN 0/200 (0%) 1/208 (0.5%) 1/208 (0.5%)
MYALGIA 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
SPINAL FRACTURE 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
ARTHRALGIA 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
BONE DISORDER 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
OSTEOPOROSIS FRACTURE 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
Nervous system disorders
CONFUSION 3/200 (1.5%) 3/208 (1.4%) 0/208 (0%)
DIZZINESS 0/200 (0%) 1/208 (0.5%) 1/208 (0.5%)
HYPOTONIA 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
PARESIS 0/200 (0%) 1/208 (0.5%) 1/208 (0.5%)
SPINAL CORD COMPRESSION 1/200 (0.5%) 1/208 (0.5%) 0/208 (0%)
AGITATION 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
AMNESIA 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
APHASIA 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
CNS DEPRESSION 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
CNS NEOPLASIA 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
COMA 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
CONVULSION 1/200 (0.5%) 0/208 (0%) 1/208 (0.5%)
DELIRIUM 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
DEPRESSION 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
DYSTONIA 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
EXTRAPYRAMIDAL SYNDROME 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
GRAND MAL CONVULSION 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
HYPESTHESIA 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
INSOMNIA 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
MENTAL STATUS CHANGES 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
NEUROPATHY 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
PARALYSIS 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
PARKINSON'S DISEASE 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
PSYCHOSIS 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
SOMNOLENCE 1/200 (0.5%) 0/208 (0%) 1/208 (0.5%)
SUICIDAL IDEATION 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
Renal and urinary disorders
ACUTE KIDNEY FAILURE 6/200 (3%) 3/208 (1.4%) 4/208 (1.9%)
GLOMERULITIS 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
KIDNEY FAILURE 1/200 (0.5%) 1/208 (0.5%) 3/208 (1.4%)
UREMIA 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
URINARY TRACT INFECTION 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
HEMATURIA 3/200 (1.5%) 0/208 (0%) 0/208 (0%)
KIDNEY FUNCTION ABNORMAL 1/200 (0.5%) 0/208 (0%) 3/208 (1.4%)
OLIGURIA 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
URINARY INCONTINENCE 0/200 (0%) 0/208 (0%) 2/208 (1%)
URINARY RETENTION 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
URINARY TRACT DISORDER 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
Respiratory, thoracic and mediastinal disorders
PNEUMONIA 3/200 (1.5%) 10/208 (4.8%) 11/208 (5.3%)
PLEURAL EFFUSION 4/200 (2%) 6/208 (2.9%) 4/208 (1.9%)
DYSPNEA 9/200 (4.5%) 2/208 (1%) 15/208 (7.2%)
PNEUMONITIS 0/200 (0%) 2/208 (1%) 0/208 (0%)
RESPIRATORY FAILURE 3/200 (1.5%) 2/208 (1%) 3/208 (1.4%)
ASTHMA 0/200 (0%) 1/208 (0.5%) 1/208 (0.5%)
BRONCHITIS 1/200 (0.5%) 1/208 (0.5%) 2/208 (1%)
CARCINOMA OF LUNG 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
HEMOTHORAX 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
PHARYNGITIS 0/200 (0%) 1/208 (0.5%) 1/208 (0.5%)
PNEUMOTHORAX 0/200 (0%) 1/208 (0.5%) 0/208 (0%)
ASPIRATION 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
BRONCHIOLITIS 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
COUGH INCREASED 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
EPISTAXIS 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
HEMOPTYSIS 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
HYPOXIA 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
LUNG EDEMA 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
LUNG FIBROSIS 1/200 (0.5%) 0/208 (0%) 0/208 (0%)
LUNG INFILTRATION NOS 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
RESPIRATORY DISORDER 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
RESPIRATORY DISTRESS SYNDROME 1/200 (0.5%) 0/208 (0%) 1/208 (0.5%)
Skin and subcutaneous tissue disorders
SKIN CARCINOMA 0/200 (0%) 0/208 (0%) 2/208 (1%)
SKIN ULCER 0/200 (0%) 0/208 (0%) 1/208 (0.5%)
Other (Not Including Serious) Adverse Events
Interferon Alfa Temsirolimus Interferon Alfa and Temsirolimus
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 197/200 (98.5%) 208/208 (100%) 205/208 (98.6%)
Blood and lymphatic system disorders
ANEMIA 78/200 (39%) 90/208 (43.3%) 123/208 (59.1%)
THROMBOCYTOPENIA 16/200 (8%) 28/208 (13.5%) 77/208 (37%)
NEUTROPENIA 26/200 (13%) 15/208 (7.2%) 57/208 (27.4%)
LEUKOPENIA 34/200 (17%) 13/208 (6.3%) 65/208 (31.3%)
LYMPHOPENIA 17/200 (8.5%) 11/208 (5.3%) 28/208 (13.5%)
Cardiac disorders
HYPERTENSION 7/200 (3.5%) 12/208 (5.8%) 12/208 (5.8%)
HYPOTENSION 11/200 (5.5%) 10/208 (4.8%) 7/208 (3.4%)
TACHYCARDIA 11/200 (5.5%) 9/208 (4.3%) 17/208 (8.2%)
VASODILATATION 5/200 (2.5%) 5/208 (2.4%) 12/208 (5.8%)
Gastrointestinal disorders
NAUSEA 82/200 (41%) 76/208 (36.5%) 84/208 (40.4%)
ANOREXIA 86/200 (43%) 66/208 (31.7%) 79/208 (38%)
DIARRHEA 39/200 (19.5%) 57/208 (27.4%) 56/208 (26.9%)
CONSTIPATION 35/200 (17.5%) 42/208 (20.2%) 39/208 (18.8%)
STOMATITIS 7/200 (3.5%) 41/208 (19.7%) 42/208 (20.2%)
MUCOSITIS 10/200 (5%) 39/208 (18.8%) 46/208 (22.1%)
VOMITING 57/200 (28.5%) 39/208 (18.8%) 60/208 (28.8%)
DRY MOUTH 16/200 (8%) 13/208 (6.3%) 12/208 (5.8%)
MOUTH ULCERATION 5/200 (2.5%) 6/208 (2.9%) 15/208 (7.2%)
ORAL MONILIASIS 4/200 (2%) 5/208 (2.4%) 15/208 (7.2%)
General disorders
ASTHENIA 126/200 (63%) 105/208 (50.5%) 127/208 (61.1%)
PAIN 30/200 (15%) 56/208 (26.9%) 41/208 (19.7%)
FEVER 98/200 (49%) 49/208 (23.6%) 126/208 (60.6%)
ABDOMINAL PAIN 34/200 (17%) 42/208 (20.2%) 34/208 (16.3%)
BACK PAIN 28/200 (14%) 41/208 (19.7%) 31/208 (14.9%)
CHEST PAIN 18/200 (9%) 35/208 (16.8%) 23/208 (11.1%)
HEADACHE 30/200 (15%) 32/208 (15.4%) 47/208 (22.6%)
INFECTION 11/200 (5.5%) 29/208 (13.9%) 32/208 (15.4%)
ALLERGIC REACTION 1/200 (0.5%) 18/208 (8.7%) 11/208 (5.3%)
CHILLS 58/200 (29%) 17/208 (8.2%) 72/208 (34.6%)
FACE EDEMA 1/200 (0.5%) 15/208 (7.2%) 10/208 (4.8%)
ACCIDENTAL INJURY 8/200 (4%) 13/208 (6.3%) 12/208 (5.8%)
FLU SYNDROME 23/200 (11.5%) 8/208 (3.8%) 28/208 (13.5%)
LAB TEST ABNORMAL 5/200 (2.5%) 8/208 (3.8%) 13/208 (6.3%)
TASTE PERVERSION 13/200 (6.5%) 31/208 (14.9%) 18/208 (8.7%)
TASTE LOSS 4/200 (2%) 11/208 (5.3%) 5/208 (2.4%)
Metabolism and nutrition disorders
HYPERLIPEMIA 29/200 (14.5%) 57/208 (27.4%) 80/208 (38.5%)
PERIPHERAL EDEMA 15/200 (7.5%) 54/208 (26%) 36/208 (17.3%)
HYPERCHOLESTEREMIA 9/200 (4.5%) 51/208 (24.5%) 55/208 (26.4%)
HYPERGLYCEMIA 22/200 (11%) 49/208 (23.6%) 36/208 (17.3%)
WEIGHT LOSS 49/200 (24.5%) 40/208 (19.2%) 65/208 (31.3%)
CREATININE INCREASED 21/200 (10.5%) 28/208 (13.5%) 42/208 (20.2%)
ALKALINE PHOSPHATASE INCREASED 15/200 (7.5%) 20/208 (9.6%) 31/208 (14.9%)
HYPOKALEMIA 7/200 (3.5%) 20/208 (9.6%) 14/208 (6.7%)
EDEMA 8/200 (4%) 19/208 (9.1%) 8/208 (3.8%)
HYPOPHOSPHATEMIA 4/200 (2%) 17/208 (8.2%) 21/208 (10.1%)
SGOT INCREASED 29/200 (14.5%) 16/208 (7.7%) 43/208 (20.7%)
HYPOPROTEINEMIA 18/200 (9%) 13/208 (6.3%) 21/208 (10.1%)
LACTIC DEHYDROGENASE INCREASED 7/200 (3.5%) 12/208 (5.8%) 19/208 (9.1%)
SGPT INCREASED 14/200 (7%) 12/208 (5.8%) 15/208 (7.2%)
HYPOCALCEMIA 21/200 (10.5%) 11/208 (5.3%) 32/208 (15.4%)
HYPERCALCEMIA 11/200 (5.5%) 8/208 (3.8%) 8/208 (3.8%)
HYPERKALEMIA 18/200 (9%) 8/208 (3.8%) 11/208 (5.3%)
DEHYDRATION 15/200 (7.5%) 7/208 (3.4%) 22/208 (10.6%)
HYPONATREMIA 7/200 (3.5%) 6/208 (2.9%) 15/208 (7.2%)
BUN INCREASED 5/200 (2.5%) 3/208 (1.4%) 11/208 (5.3%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA 29/200 (14.5%) 38/208 (18.3%) 27/208 (13%)
MYALGIA 30/200 (15%) 16/208 (7.7%) 22/208 (10.6%)
BONE PAIN 11/200 (5.5%) 8/208 (3.8%) 7/208 (3.4%)
Nervous system disorders
INSOMNIA 29/200 (14.5%) 25/208 (12%) 36/208 (17.3%)
DIZZINESS 25/200 (12.5%) 18/208 (8.7%) 27/208 (13%)
ANXIETY 12/200 (6%) 16/208 (7.7%) 24/208 (11.5%)
PARESTHESIA 10/200 (5%) 14/208 (6.7%) 13/208 (6.3%)
SOMNOLENCE 21/200 (10.5%) 14/208 (6.7%) 14/208 (6.7%)
DEPRESSION 26/200 (13%) 9/208 (4.3%) 25/208 (12%)
CONFUSION 17/200 (8.5%) 6/208 (2.9%) 10/208 (4.8%)
Renal and urinary disorders
URINARY TRACT INFECTION 10/200 (5%) 16/208 (7.7%) 23/208 (11.1%)
Respiratory, thoracic and mediastinal disorders
DYSPNEA 42/200 (21%) 59/208 (28.4%) 51/208 (24.5%)
COUGH INCREASED 29/200 (14.5%) 55/208 (26.4%) 49/208 (23.6%)
EPISTAXIS 7/200 (3.5%) 27/208 (13%) 27/208 (13%)
PHARYNGITIS 3/200 (1.5%) 24/208 (11.5%) 27/208 (13%)
RHINITIS 4/200 (2%) 20/208 (9.6%) 10/208 (4.8%)
UPPER RESPIRATORY INFECTION 1/200 (0.5%) 14/208 (6.7%) 7/208 (3.4%)
Skin and subcutaneous tissue disorders
RASH 11/200 (5.5%) 76/208 (36.5%) 34/208 (16.3%)
PRURITUS 16/200 (8%) 40/208 (19.2%) 24/208 (11.5%)
NAIL DISORDER 1/200 (0.5%) 28/208 (13.5%) 5/208 (2.4%)
DRY SKIN 14/200 (7%) 22/208 (10.6%) 13/208 (6.3%)
ACNE 2/200 (1%) 21/208 (10.1%) 7/208 (3.4%)
EXFOLIATIVE DERMATITIS 1/200 (0.5%) 16/208 (7.7%) 6/208 (2.9%)
PRURITIC RASH 1/200 (0.5%) 11/208 (5.3%) 3/208 (1.4%)
SKIN DISORDER 1/200 (0.5%) 11/208 (5.3%) 6/208 (2.9%)
SWEATING 14/200 (7%) 5/208 (2.4%) 15/208 (7.2%)

Limitations/Caveats

Efficacy data was not collected or analyzed after the primary analysis was completed.

More Information

Certain Agreements

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

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

Name/Title Pfizer ClinicalTrials.gov Call Center
Organization Pfizer, Inc.
Phone 1-800-718-1021
Email ClinicalTrials.gov_Inquiries@pfizer.com
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00065468
Other Study ID Numbers:
  • 3066K1-304
  • NCT00070330
First Posted:
Jul 25, 2003
Last Update Posted:
Oct 25, 2012
Last Verified:
Sep 1, 2012