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

• ClinicalTrials.gov Identifier: NCT00474786
• Recruitment Status: Completed
• First Posted: May 17, 2007
• Results First Posted: March 7, 2013
• Last Update Posted: November 21, 2013
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: May 15, 2007
• First Posted Date: May 17, 2007
• Results First Submitted Date: January 31, 2013
• Results First Posted Date: March 7, 2013
• Last Update Posted Date: November 21, 2013
• Study Start Date: September 2007
• Actual Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 31, 2013)

Progression-Free Survival (PFS) [ Time Frame: Baseline up to 24 Months ]

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.

• Original Primary Outcome Measures (submitted: May 15, 2007): To compare: safety,tolerability and efficacy (as measured by PFS), of temsirolimus and sorafenib when used as single agents in the second-line setting in subjects with advanced RCC who have failed prior first-line treatment with sunitinib.

Current Secondary Outcome Measures (submitted: January 31, 2013)

• Progression Free Survival (PFS) by Investigator Assessment [ Time Frame: Baseline up to 24 Months ]
  Interval from date of randomization until documentation of PD by an investigator tumor assessment, symptomatic deterioration, or death for any reason whichever occurred first.
• Percentage of Participants With Tumor Response [ Time Frame: Baseline up to 24 Months ]
  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.
• Overall Survival (OS) [ Time Frame: Baseline to date of death from any cause (up to 24 months) ]
  Overall survival was the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.
• Percentage of Participants With PFS Events at 12, 24 and 36 Weeks by Independent Assessment [ Time Frame: Weeks 12, 24, and 36 ]
  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.
• Duration of Response (DR) [ Time Frame: Baseline up to 24 Months ]
  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.

• Original Secondary Outcome Measures (submitted: May 15, 2007): Secondary Endpoints: Response rate (CR and PR) by RECIST criteria: OS; SD at 12, 24, and 36 weeks; Clinical benefit (CR + PR + SD >24 weeks);Duration of response;Best tumor shrinkage

Current Other Pre-specified Outcome Measures (submitted: January 31, 2013)

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 24 months ]

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.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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).
• 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.

Study Arms

• Experimental: 1
  Intervention: Drug: Sorafenib
• Experimental: 2
  Intervention: Drug: temsirolimus (Torisel)

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 18, 2012): 512
• Original Enrollment (submitted: May 15, 2007): 440
• Actual Study Completion Date: January 2013
• Actual Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Canada, Chile, China, Denmark, Finland, France, Germany, Hungary, Italy, Korea, Republic of, Netherlands, Singapore, Spain, Sweden, Switzerland, United Kingdom, United States
• Removed Location Countries: Hong Kong

Administrative Information

• NCT Number: NCT00474786
• Other Study ID Numbers: 3066K1-404; B1771003
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pfizer
• Original Responsible Party: Not Provided
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer
• Collaborators: Not Provided

Investigators

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

• PRS Account: Pfizer
• Verification Date: October 2013