Temsirolimus Versus Sorafenib As Second-Line Therapy In Patients With Advanced RCC Who Have Failed First-Line Sunitinib

Renal Cell Carcinoma Clinical Trial

— INTORSECT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00474786
• Other study ID #: 3066K1-404
• Secondary ID: B1771003
• Status: Completed
• Phase: Phase 3
• First received: May 15, 2007
• Last updated: October 28, 2013
• Start date: September 2007
• Est. completion date: January 2013

Study information

• Verified date: October 2013
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 512
• Est. completion date: January 2013
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

Drug:
• Sorafenib
Subjects randomized to arm B will take sorafenib 400 mg (2 x 200 mg tablets) PO, BID (total daily dose of 800 mg).
• temsirolimus (Torisel)
Subjects randomized to arm A will receive temsirolimus (Torisel) 25 mg via IV infusion once weekly. This infusion is to be administered over a 30-60 minute period. Subjects are to be pre-treated with 25-50 mg IV diphenhydramine (or comparable IV antihistamine) approximately 30 minutes before temsirolimus infusion.

Locations

Country	Name	City	State
Argentina	Pfizer Investigational Site	Buenos Aires
Argentina	Pfizer Investigational Site	Buenos Aires
Argentina	Pfizer Investigational Site	Buenos Aires
Argentina	Pfizer Investigational Site	Nueva Cordoba
Argentina	Pfizer Investigational Site	Rosario	Santa Fé
Argentina	Pfizer Investigational Site	Tucuman
Australia	Pfizer Investigational Site	Adelaide	South Australia
Australia	Pfizer Investigational Site	Elizabeth Vale	South Australia
Australia	Pfizer Investigational Site	Kogarah	New South Wales
Australia	Pfizer Investigational Site	South Brisbane	Queensland
Australia	Pfizer Investigational Site	St Leonards	New South Wales
Australia	Pfizer Investigational Site	Westmead	New South Wales
Australia	Pfizer Investigational Site	Woodville South	South Australia
Austria	Pfizer Investigational Site	Salzburg
Austria	Pfizer Investigational Site	Wien
Canada	Pfizer Investigational Site	Cornwall	Ontario
Canada	Pfizer Investigational Site	Edmonton	Alberta
Canada	Pfizer Investigational Site	Halifax	Nova Scotia
Canada	Pfizer Investigational Site	Halifax	Nova Scotia
Canada	Pfizer Investigational Site	Halifax	Nova Scotia
Canada	Pfizer Investigational Site	Hamilton	Ontario
Canada	Pfizer Investigational Site	Kelowna	British Columbia
Canada	Pfizer Investigational Site	London	Ontario
Canada	Pfizer Investigational Site	London	Ontario
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Ottawa	Ontario
Canada	Pfizer Investigational Site	Ottawa	Ontario
Canada	Pfizer Investigational Site	Toronto	Ontario
Canada	Pfizer Investigational Site	Toronto	Ontario
Canada	Pfizer Investigational Site	Vancouver	British Columbia
Canada	Pfizer Investigational Site	Victoria	British Columbia
Chile	Pfizer Investigational Site	Providencia	Santiago
China	Pfizer Investigational Site	Hong Kong
Denmark	Pfizer Investigational Site	Aarhus C
Denmark	Pfizer Investigational Site	Herlev
Finland	Pfizer Investigational Site	Tampere
Finland	Pfizer Investigational Site	Turku
France	Pfizer Investigational Site	Angers
France	Pfizer Investigational Site	Besancon
France	Pfizer Investigational Site	Bordeaux
France	Pfizer Investigational Site	Caen Cedex 05
France	Pfizer Investigational Site	Clermont-Ferrand Cedex 1
France	Pfizer Investigational Site	Dijon
France	Pfizer Investigational Site	Lille
France	Pfizer Investigational Site	Lyon Cedex 08
France	Pfizer Investigational Site	Marseille Cedex 9
France	Pfizer Investigational Site	Montpellier	Cedex 5
France	Pfizer Investigational Site	Paris Cedex 15
France	Pfizer Investigational Site	Poitiers Cedex
France	Pfizer Investigational Site	Saint Herlain/Nantes Cedex
France	Pfizer Investigational Site	Strasbourg
France	Pfizer Investigational Site	Vandoeuvre Les Nancy
France	Pfizer Investigational Site	Villejuif Cedex
Germany	Pfizer Investigational Site	Berlin
Germany	Pfizer Investigational Site	Dresden
Germany	Pfizer Investigational Site	Heidelberg
Germany	Pfizer Investigational Site	Kassel
Germany	Pfizer Investigational Site	Luebeck
Germany	Pfizer Investigational Site	Muenchen
Germany	Pfizer Investigational Site	Neuss
Germany	Pfizer Investigational Site	Ulm
Hungary	Pfizer Investigational Site	Budapest
Italy	Pfizer Investigational Site	Chieti
Italy	Pfizer Investigational Site	Firenze
Italy	Pfizer Investigational Site	Napoli
Italy	Pfizer Investigational Site	Pavia
Italy	Pfizer Investigational Site	Roma
Italy	Pfizer Investigational Site	Roma
Italy	Pfizer Investigational Site	Roma
Korea, Republic of	Pfizer Investigational Site	Seoul
Korea, Republic of	Pfizer Investigational Site	Seoul
Korea, Republic of	Pfizer Investigational Site	Seoul
Korea, Republic of	Pfizer Investigational Site	Seoul
Netherlands	Pfizer Investigational Site	Dordrecht
Netherlands	Pfizer Investigational Site	Leeuwarden
Netherlands	Pfizer Investigational Site	Zwolle
Singapore	Pfizer Investigational Site	Singapore
Spain	Pfizer Investigational Site	Badalona	Barcelona
Spain	Pfizer Investigational Site	Barcelona
Spain	Pfizer Investigational Site	Madrid
Spain	Pfizer Investigational Site	Madrid
Spain	Pfizer Investigational Site	Oviedo	Asturias
Spain	Pfizer Investigational Site	Sabadell	Barcelona
Spain	Pfizer Investigational Site	Sevilla
Spain	Pfizer Investigational Site	Valencia
Sweden	Pfizer Investigational Site	Göteborg
Sweden	Pfizer Investigational Site	Lund
Sweden	Pfizer Investigational Site	Malmo
Switzerland	Pfizer Investigational Site	Basel
Switzerland	Pfizer Investigational Site	Basel	BS
Switzerland	Pfizer Investigational Site	Bruderholz
Switzerland	Pfizer Investigational Site	Geneva	GE
Switzerland	Pfizer Investigational Site	Kleinriehenstrasse 30	Basel
Switzerland	Pfizer Investigational Site	Luzern
Switzerland	Pfizer Investigational Site	Rheinstrasse 26
United Kingdom	Pfizer Investigational Site	Birmingham
United Kingdom	Pfizer Investigational Site	Cambridge	Cambridgeshire
United Kingdom	Pfizer Investigational Site	Edgbaston	Birmingham
United Kingdom	Pfizer Investigational Site	London
United Kingdom	Pfizer Investigational Site	Manchester
United Kingdom	Pfizer Investigational Site	Newcastle upon Tyne
United Kingdom	Pfizer Investigational Site	Withington	Manchester
United States	Pfizer Investigational Site	Austin	Texas
United States	Pfizer Investigational Site	Baltimore	Maryland
United States	Pfizer Investigational Site	Bethesda	Maryland
United States	Pfizer Investigational Site	Cleveland	Ohio
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Duarte	California
United States	Pfizer Investigational Site	La Jolla	California
United States	Pfizer Investigational Site	La Jolla	California
United States	Pfizer Investigational Site	Los Angeles	California
United States	Pfizer Investigational Site	Los Angeles	California
United States	Pfizer Investigational Site	Louisville	Kentucky
United States	Pfizer Investigational Site	Meriden	Connecticut
United States	Pfizer Investigational Site	Metairie	Louisiana
United States	Pfizer Investigational Site	Municie	Indiana
United States	Pfizer Investigational Site	New York	New York
United States	Pfizer Investigational Site	Oklahoma City	Oklahoma
United States	Pfizer Investigational Site	Orange	California
United States	Pfizer Investigational Site	Riverside	California
United States	Pfizer Investigational Site	Salt Lake City	Utah
United States	Pfizer Investigational Site	Salt Lake City	Utah
United States	Pfizer Investigational Site	San Antonio	Texas
United States	Pfizer Investigational Site	San Diego	California
United States	Pfizer Investigational Site	Seattle	Washington
United States	Pfizer Investigational Site	Tulsa	Oklahoma
United States	Pfizer Investigational Site	Tupelo	Mississippi

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Canada,  Chile,  China,  Denmark,  Finland,  France,  Germany,  Hungary,  Italy,  Korea, Republic of,  Netherlands,  Singapore,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to [study drug] was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.	Baseline up to 24 months	Yes
Primary	Progression-Free Survival (PFS)	Interval from date of randomization until documentation of progressive disease (PD) by an independent tumor assessment according to Response Evaluation Criteria in Solid Tumor (RECIST) or death for any reason whichever occurred first.	Baseline up to 24 Months	Yes
Secondary	Progression Free Survival (PFS) by Investigator Assessment	Interval from date of randomization until documentation of PD by an investigator tumor assessment, symptomatic deterioration, or death for any reason whichever occurred first.	Baseline up to 24 Months	No
Secondary	Percentage of Participants With Tumor Response	Percentage of participants with tumor response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST and evaluated by independent central review. CR/PR persisted on repeat imaging study at least 4 weeks after initial documentation of response. PR had at least 30 percent decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.	Baseline up to 24 Months	No
Secondary	Overall Survival (OS)	Overall survival was the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.	Baseline to date of death from any cause (up to 24 months)	No
Secondary	Percentage of Participants With PFS Events at 12, 24 and 36 Weeks by Independent Assessment	PFS: Interval from date of randomization until documentation of PD by an independent tumor assessment according to RECIST or death for any reason whichever occurred first. PFS calculated as (Weeks)=(randomization date minus first dose date plus 1) divided by 7.	Weeks 12, 24, and 36	No
Secondary	Duration of Response (DR)	Duration of response as defined by the time from CR or PR (whichever status recorded first) until the date of death or PD was objectively documented. Median and its 95 percent confidence interval (95% CI) were estimated using Kaplan-Meier method.	Baseline up to 24 Months	No

External Links

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