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

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Cell Carcinoma
• Intervention / Treatment: Drug: Sorafenib; Drug: temsirolimus (Torisel)

• Study Type: Interventional
• Enrollment (Actual): 512
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1437JCP
    • Pfizer Investigational Site
  • Buenos Aires, Argentina, C1426ANZ
    • Pfizer Investigational Site
  • Buenos Aires, Argentina, C1122AAL
    • Pfizer Investigational Site
  • Nueva Cordoba, Argentina, X5006HBF
    • Pfizer Investigational Site
  • Tucuman, Argentina, T4000 IAK
    • Pfizer Investigational Site
  • Santa Fé
    • Rosario, Santa Fé, Argentina, S2000KZE
      • Pfizer Investigational Site
• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Pfizer Investigational Site
    • St Leonards, New South Wales, Australia, 2065
      • Pfizer Investigational Site
    • Westmead, New South Wales, Australia, 2145
      • Pfizer Investigational Site
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Pfizer Investigational Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Pfizer Investigational Site
    • Elizabeth Vale, South Australia, Australia, 5112
      • Pfizer Investigational Site
    • Woodville South, South Australia, Australia, 5011
      • Pfizer Investigational Site
• Austria
  • Salzburg, Austria, 5020
    • Pfizer Investigational Site
  • Wien, Austria, 1090
    • Pfizer Investigational Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Pfizer Investigational Site
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • Pfizer Investigational Site
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Pfizer Investigational Site
    • Victoria, British Columbia, Canada, V8R 6V5
      • Pfizer Investigational Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Pfizer Investigational Site
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • Pfizer Investigational Site
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Pfizer Investigational Site
  • Ontario
    • Cornwall, Ontario, Canada, K6R 5S5
      • Pfizer Investigational Site
    • Hamilton, Ontario, Canada, L8N 4A6
      • Pfizer Investigational Site
    • London, Ontario, Canada, N6A 4G5
      • Pfizer Investigational Site
    • London, Ontario, Canada, N6A 4L6
      • Pfizer Investigational Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Pfizer Investigational Site
    • Ottawa, Ontario, Canada, K1Y 4K7
      • Pfizer Investigational Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Pfizer Investigational Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Pfizer Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H3G 1A4
      • Pfizer Investigational Site
• Chile
  • Santiago
    • Providencia, Santiago, Chile
      • Pfizer Investigational Site
• China
  • Hong Kong, China
    • Pfizer Investigational Site
• Denmark
  • Aarhus C, Denmark, 8000
    • Pfizer Investigational Site
  • Herlev, Denmark, 2730
    • Pfizer Investigational Site
• Finland
  • Tampere, Finland, 33 521
    • Pfizer Investigational Site
  • Turku, Finland, 20 520
    • Pfizer Investigational Site
• France
  • Angers, France, 49100
    • Pfizer Investigational Site
  • Besancon, France, 25000
    • Pfizer Investigational Site
  • Bordeaux, France, 33075
    • Pfizer Investigational Site
  • Caen Cedex 05, France, 14076
    • Pfizer Investigational Site
  • Clermont-Ferrand Cedex 1, France, 63011
    • Pfizer Investigational Site
  • Dijon, France, 21079
    • Pfizer Investigational Site
  • Lille, France, 59000
    • Pfizer Investigational Site
  • Lyon Cedex 08, France, 69373
    • Pfizer Investigational Site
  • Marseille Cedex 9, France, 13273
    • Pfizer Investigational Site
  • Paris Cedex 15, France, 75908
    • Pfizer Investigational Site
  • Poitiers Cedex, France, 86021
    • Pfizer Investigational Site
  • Saint Herlain/Nantes Cedex, France, 44805
    • Pfizer Investigational Site
  • Strasbourg, France, 67091
    • Pfizer Investigational Site
  • Vandoeuvre Les Nancy, France, 54511
    • Pfizer Investigational Site
  • Villejuif Cedex, France, 94805
    • Pfizer Investigational Site
  • Cedex 5
    • Montpellier, Cedex 5, France, 34298
      • Pfizer Investigational Site
• Germany
  • Berlin, Germany, 10117
    • Pfizer Investigational Site
  • Dresden, Germany, 01307
    • Pfizer Investigational Site
  • Heidelberg, Germany, 69120
    • Pfizer Investigational Site
  • Kassel, Germany, 34125
    • Pfizer Investigational Site
  • Luebeck, Germany, 23538
    • Pfizer Investigational Site
  • Muenchen, Germany, 81675
    • Pfizer Investigational Site
  • Neuss, Germany, 41464
    • Pfizer Investigational Site
  • Ulm, Germany, 89081
    • Pfizer Investigational Site
• Hungary
  • Budapest, Hungary, H-1122
    • Pfizer Investigational Site
• Italy
  • Chieti, Italy, 66013
    • Pfizer Investigational Site
  • Firenze, Italy, 50134
    • Pfizer Investigational Site
  • Napoli, Italy, 80131
    • Pfizer Investigational Site
  • Pavia, Italy, 27100
    • Pfizer Investigational Site
  • Roma, Italy, 00144
    • Pfizer Investigational Site
  • Roma, Italy, 00152
    • Pfizer Investigational Site
  • Roma, Italy, 0144
    • Pfizer Investigational Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 138-736
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 110-744
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 135-710
    • Pfizer Investigational Site
• Netherlands
  • Dordrecht, Netherlands, 3318 AT
    • Pfizer Investigational Site
  • Leeuwarden, Netherlands, 8934 AD
    • Pfizer Investigational Site
  • Zwolle, Netherlands, 8025 AB
    • Pfizer Investigational Site
• Singapore
  • Singapore, Singapore, 169610
    • Pfizer Investigational Site
• Spain
  • Barcelona, Spain, 08025
    • Pfizer Investigational Site
  • Madrid, Spain, 28007
    • Pfizer Investigational Site
  • Madrid, Spain, 28041
    • Pfizer Investigational Site
  • Sevilla, Spain, 41013
    • Pfizer Investigational Site
  • Valencia, Spain, 46010
    • Pfizer Investigational Site
  • Asturias
    • Oviedo, Asturias, Spain, 33006
      • Pfizer Investigational Site
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Pfizer Investigational Site
    • Sabadell, Barcelona, Spain, 08208
      • Pfizer Investigational Site
• Sweden
  • Göteborg, Sweden, SE-413 45
    • Pfizer Investigational Site
  • Lund, Sweden, 221 85
    • Pfizer Investigational Site
  • Malmo, Sweden, 205 02
    • Pfizer Investigational Site
• Switzerland
  • Basel, Switzerland
    • Pfizer Investigational Site
  • Bruderholz, Switzerland
    • Pfizer Investigational Site
  • Luzern, Switzerland, 6000
    • Pfizer Investigational Site
  • Rheinstrasse 26, Switzerland
    • Pfizer Investigational Site
  • BS
    • Basel, BS, Switzerland, 4031
      • Pfizer Investigational Site
  • Basel
    • Kleinriehenstrasse 30, Basel, Switzerland
      • Pfizer Investigational Site
  • GE
    • Geneva, GE, Switzerland, 1221
      • Pfizer Investigational Site
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Pfizer Investigational Site
  • London, United Kingdom, SE1 9RT
    • Pfizer Investigational Site
  • Manchester, United Kingdom, M23 9LT
    • Pfizer Investigational Site
  • Newcastle upon Tyne, United Kingdom, NE4 6BE
    • Pfizer Investigational Site
  • Birmingham
    • Edgbaston, Birmingham, United Kingdom, B5 7UG
      • Pfizer Investigational Site
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Pfizer Investigational Site
  • Manchester
    • Withington, Manchester, United Kingdom, M20 4BX
      • Pfizer Investigational Site
• United States
  • California
    • Duarte, California, United States, 91010
      • Pfizer Investigational Site
    • La Jolla, California, United States, 92037
      • Pfizer Investigational Site
    • La Jolla, California, United States, 92093
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90095
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90095-6984
      • Pfizer Investigational Site
    • Orange, California, United States, 92868
      • Pfizer Investigational Site
    • Riverside, California, United States, 92505
      • Pfizer Investigational Site
    • San Diego, California, United States, 92103
      • Pfizer Investigational Site
  • Connecticut
    • Meriden, Connecticut, United States, 06451
      • Pfizer Investigational Site
  • Indiana
    • Municie, Indiana, United States, 47303
      • Pfizer Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Pfizer Investigational Site
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Pfizer Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Pfizer Investigational Site
    • Bethesda, Maryland, United States, 20817
      • Pfizer Investigational Site
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Pfizer Investigational Site
  • New York
    • New York, New York, United States, 10065
      • Pfizer Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Pfizer Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Pfizer Investigational Site
    • Tulsa, Oklahoma, United States, 74104
      • Pfizer Investigational Site
  • Texas
    • Austin, Texas, United States, 78731
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75246
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75226
      • Pfizer Investigational Site
    • San Antonio, Texas, United States, 78229
      • Pfizer Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84112-5550
      • Pfizer Investigational Site
    • Salt Lake City, Utah, United States, 84412
      • Pfizer Investigational Site
  • Washington
    • Seattle, Washington, United States, 98101
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	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).
Experimental: 2	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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)
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: May 15, 2007
• First Submitted That Met QC Criteria: May 15, 2007
• First Posted (Estimate): May 17, 2007

Study Record Updates

• Last Update Posted (Estimate): November 21, 2013
• Last Update Submitted That Met QC Criteria: October 28, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Metastatic or Advanced Renal Cell Carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Protein Kinase Inhibitors; Antibiotics, Antineoplastic; Antifungal Agents; Sorafenib; Sirolimus
• Other Study ID Numbers: 3066K1-404; B1771003