Clinical trial NCT00474786: Temsirolimus Versus Sorafenib As Second-Line Therapy In Patients With Advanced RCC Who Have Failed First-Line Sunitinib
Official title: A Randomized Trial Of Temsirolimus Versus Sorafenib As Second-Line Therapy In Patients With Advanced Renal Cell Carcinoma Who Have Failed First-Line Sunitinib Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Renal Cell Carcinoma
Keywords: Metastatic or Advanced Renal Cell Carcinoma
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2007-05-17
Enrollment: 512
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an international, randomized, open-label, outpatient, multicenter study. Subjects will be assigned in a 1:1 ratio to 1 of 2 treatment arms: temsirolimus 25 mg once weekly by intravenous (IV) infusion or sorafenib 400 mg by mouth (PO) twice daily (BID). These investigational drugs will be administered in 6-week cycles for the duration of the study, up to 24 months. Subjects will be stratified by nephrectomy status, duration of response to sunitinib therapy, Memorial Sloan Kettering Cancer Center (MSKCC) prognostic group, and RCC tumor histology.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed diagnosis of mRCC (regardless of histology or nephrectomy status) with well-documented Radiological PD by RECIST criteria or clinical PD as judged by the investigator while receiving first-line sunitinib therapy. Subjects must have at least 1 cycle of sunitinib therapy (minimum of four weeks continuously).
* At time of randomization, at least 2 weeks since prior treatment with sunitinib, palliative radiation therapy, and/or surgery.
* At time of randomization, there must be at least 1 measurable lesion per RECIST. Lesions that have been previously irradiated or embolized cannot be selected as target lesions.

  * More criteria apply

Exclusion Criteria:

* Metastatic CNS from RCC.
* Subjects who discontinued Sutent therapy due specifically to intolerance.
* Prior systemic therapy for mRCC other than sunitinib.
* Active ketonuria, secondary to poorly controlled diabetes mellitus

  * More criteria apply

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Baseline up to 24 Months
Secondary outcomes:
measure: Progression Free Survival (PFS) by Investigator Assessment
timeFrame: Baseline up to 24 Months
measure: Percentage of Participants With Tumor Response
timeFrame: Baseline up to 24 Months
measure: Overall Survival (OS)
timeFrame: Baseline to date of death from any cause (up to 24 months)
measure: Percentage of Participants With PFS Events at 12, 24 and 36 Weeks by Independent Assessment
timeFrame: Weeks 12, 24, and 36
measure: Duration of Response (DR)
timeFrame: Baseline up to 24 Months
Other outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 24 months
Locations:
city: Duarte
country: United States
facility: Pfizer Investigational Site
state: California
city: La Jolla
country: United States
facility: Pfizer Investigational Site
state: California
city: La Jolla
country: United States
facility: Pfizer Investigational Site
state: California
city: Los Angeles
country: United States
facility: Pfizer Investigational Site
state: California
city: Los Angeles
country: United States
facility: Pfizer Investigational Site
state: California
city: Orange
country: United States
facility: Pfizer Investigational Site
state: California
city: Riverside
country: United States
facility: Pfizer Investigational Site
state: California
city: San Diego
country: United States
facility: Pfizer Investigational Site
state: California
city: Meriden
country: United States
facility: Pfizer Investigational Site
state: Connecticut
city: Municie
country: United States
facility: Pfizer Investigational Site
state: Indiana
city: Louisville
country: United States
facility: Pfizer Investigational Site
state: Kentucky
city: Metairie
country: United States
facility: Pfizer Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: Pfizer Investigational Site
state: Maryland
city: Bethesda
country: United States
facility: Pfizer Investigational Site
state: Maryland
city: Tupelo
country: United States
facility: Pfizer Investigational Site
state: Mississippi
city: New York
country: United States
facility: Pfizer Investigational Site
state: New York
city: Cleveland
country: United States
facility: Pfizer Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: Pfizer Investigational Site
state: Oklahoma
city: Tulsa
country: United States
facility: Pfizer Investigational Site
state: Oklahoma
city: Austin
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Dallas
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Dallas
country: United States
facility: Pfizer Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Salt Lake City
country: United States
facility: Pfizer Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: Pfizer Investigational Site
state: Utah
city: Seattle
country: United States
facility: Pfizer Investigational Site
state: Washington
city: Rosario
country: Argentina
facility: Pfizer Investigational Site
state: Santa Fé
city: Buenos Aires
country: Argentina
facility: Pfizer Investigational Site
city: Buenos Aires
country: Argentina
facility: Pfizer Investigational Site
city: Buenos Aires
country: Argentina
facility: Pfizer Investigational Site
city: Nueva Cordoba
country: Argentina
facility: Pfizer Investigational Site
city: Tucuman
country: Argentina
facility: Pfizer Investigational Site
city: Kogarah
country: Australia
facility: Pfizer Investigational Site
state: New South Wales
city: St Leonards
country: Australia
facility: Pfizer Investigational Site
state: New South Wales
city: Westmead
country: Australia
facility: Pfizer Investigational Site
state: New South Wales
city: South Brisbane
country: Australia
facility: Pfizer Investigational Site
state: Queensland
city: Adelaide
country: Australia
facility: Pfizer Investigational Site
state: South Australia
city: Elizabeth Vale
country: Australia
facility: Pfizer Investigational Site
state: South Australia
city: Woodville South
country: Australia
facility: Pfizer Investigational Site
state: South Australia
city: Salzburg
country: Austria
facility: Pfizer Investigational Site
city: Wien
country: Austria
facility: Pfizer Investigational Site
city: Edmonton
country: Canada
facility: Pfizer Investigational Site
state: Alberta
city: Kelowna
country: Canada
facility: Pfizer Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: Pfizer Investigational Site
state: British Columbia
city: Victoria
country: Canada
facility: Pfizer Investigational Site
state: British Columbia
city: Halifax
country: Canada
facility: Pfizer Investigational Site
state: Nova Scotia
city: Halifax
country: Canada
facility: Pfizer Investigational Site
state: Nova Scotia
city: Halifax
country: Canada
facility: Pfizer Investigational Site
state: Nova Scotia
city: Cornwall
country: Canada
facility: Pfizer Investigational Site
state: Ontario
city: Hamilton
country: Canada
facility: Pfizer Investigational Site
state: Ontario
city: London
country: Canada
facility: Pfizer Investigational Site
state: Ontario
city: London
country: Canada
facility: Pfizer Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: Pfizer Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: Pfizer Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Pfizer Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Pfizer Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: Pfizer Investigational Site
state: Quebec
city: Providencia
country: Chile
facility: Pfizer Investigational Site
state: Santiago
city: Hong Kong
country: China
facility: Pfizer Investigational Site
city: Aarhus C
country: Denmark
facility: Pfizer Investigational Site
city: Herlev
country: Denmark
facility: Pfizer Investigational Site
city: Tampere
country: Finland
facility: Pfizer Investigational Site
city: Turku
country: Finland
facility: Pfizer Investigational Site
city: Montpellier
country: France
facility: Pfizer Investigational Site
state: Cedex 5
city: Angers
country: France
facility: Pfizer Investigational Site
city: Besancon
country: France
facility: Pfizer Investigational Site
city: Bordeaux
country: France
facility: Pfizer Investigational Site
city: Caen Cedex 05
country: France
facility: Pfizer Investigational Site
city: Clermont-Ferrand Cedex 1
country: France
facility: Pfizer Investigational Site
city: Dijon
country: France
facility: Pfizer Investigational Site
city: Lille
country: France
facility: Pfizer Investigational Site
city: Lyon Cedex 08
country: France
facility: Pfizer Investigational Site
city: Marseille Cedex 9
country: France
facility: Pfizer Investigational Site
city: Paris Cedex 15
country: France
facility: Pfizer Investigational Site
city: Poitiers Cedex
country: France
facility: Pfizer Investigational Site
city: Saint Herlain/Nantes Cedex
country: France
facility: Pfizer Investigational Site
city: Strasbourg
country: France
facility: Pfizer Investigational Site
city: Vandoeuvre Les Nancy
country: France
facility: Pfizer Investigational Site
city: Villejuif Cedex
country: France
facility: Pfizer Investigational Site
city: Berlin
country: Germany
facility: Pfizer Investigational Site
city: Dresden
country: Germany
facility: Pfizer Investigational Site
city: Heidelberg
country: Germany
facility: Pfizer Investigational Site
city: Kassel
country: Germany
facility: Pfizer Investigational Site
city: Luebeck
country: Germany
facility: Pfizer Investigational Site
city: Muenchen
country: Germany
facility: Pfizer Investigational Site
city: Neuss
country: Germany
facility: Pfizer Investigational Site
city: Ulm
country: Germany
facility: Pfizer Investigational Site
city: Budapest
country: Hungary
facility: Pfizer Investigational Site
city: Chieti
country: Italy
facility: Pfizer Investigational Site
city: Firenze
country: Italy
facility: Pfizer Investigational Site
city: Napoli
country: Italy
facility: Pfizer Investigational Site
city: Pavia
country: Italy
facility: Pfizer Investigational Site
city: Roma
country: Italy
facility: Pfizer Investigational Site
city: Roma
country: Italy
facility: Pfizer Investigational Site
city: Roma
country: Italy
facility: Pfizer Investigational Site
city: Seoul
country: Korea, Republic of
facility: Pfizer Investigational Site
city: Seoul
country: Korea, Republic of
facility: Pfizer Investigational Site
city: Seoul
country: Korea, Republic of
facility: Pfizer Investigational Site
city: Seoul
country: Korea, Republic of
facility: Pfizer Investigational Site
city: Dordrecht
country: Netherlands
facility: Pfizer Investigational Site
city: Leeuwarden
country: Netherlands
facility: Pfizer Investigational Site
city: Zwolle
country: Netherlands
facility: Pfizer Investigational Site
city: Singapore
country: Singapore
facility: Pfizer Investigational Site
city: Oviedo
country: Spain
facility: Pfizer Investigational Site
state: Asturias
city: Badalona
country: Spain
facility: Pfizer Investigational Site
state: Barcelona
city: Sabadell
country: Spain
facility: Pfizer Investigational Site
state: Barcelona
city: Barcelona
country: Spain
facility: Pfizer Investigational Site
city: Madrid
country: Spain
facility: Pfizer Investigational Site
city: Madrid
country: Spain
facility: Pfizer Investigational Site
city: Sevilla
country: Spain
facility: Pfizer Investigational Site
city: Valencia
country: Spain
facility: Pfizer Investigational Site
city: Göteborg
country: Sweden
facility: Pfizer Investigational Site
city: Lund
country: Sweden
facility: Pfizer Investigational Site
city: Malmo
country: Sweden
facility: Pfizer Investigational Site
city: Kleinriehenstrasse 30
country: Switzerland
facility: Pfizer Investigational Site
state: Basel
city: Basel
country: Switzerland
facility: Pfizer Investigational Site
state: BS
city: Geneva
country: Switzerland
facility: Pfizer Investigational Site
state: GE
city: Basel
country: Switzerland
facility: Pfizer Investigational Site
city: Bruderholz
country: Switzerland
facility: Pfizer Investigational Site
city: Luzern
country: Switzerland
facility: Pfizer Investigational Site
city: Rheinstrasse 26
country: Switzerland
facility: Pfizer Investigational Site
city: Edgbaston
country: United Kingdom
facility: Pfizer Investigational Site
state: Birmingham
city: Cambridge
country: United Kingdom
facility: Pfizer Investigational Site
state: Cambridgeshire
city: Withington
country: United Kingdom
facility: Pfizer Investigational Site
state: Manchester
city: Birmingham
country: United Kingdom
facility: Pfizer Investigational Site
city: London
country: United Kingdom
facility: Pfizer Investigational Site
city: Manchester
country: United Kingdom
facility: Pfizer Investigational Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Grunwald 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.
citation: Hutson TE, Escudier B, Esteban E, Bjarnason GA, Lim HY, Pittman KB, Senico P, Niethammer A, Lu DR, Hariharan S, Motzer RJ. Randomized phase III trial of temsirolimus versus sorafenib as second-line therapy after sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Mar 10;32(8):760-7. doi: 10.1200/JCO.2013.50.3961. Epub 2013 Dec 2.