Study Evaluating The Safety, Efficacy & Pharmacokinetics Of Temsirolimus(CCI-779) In Subjects With Advanced Renal Cell Carcinoma

• ClinicalTrials.gov Identifier: NCT00494091
• Recruitment Status: Completed
• First Posted: June 29, 2007
• Results First Posted: July 9, 2012
• Last Update Posted: March 21, 2013
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: June 28, 2007
• First Posted Date: June 29, 2007
• Results First Submitted Date: May 31, 2012
• Results First Posted Date: July 9, 2012
• Last Update Posted Date: March 21, 2013
• Study Start Date: February 2007
• Actual Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 31, 2012)

Percentage of Participants With Clinical Benefit [ Time Frame: Baseline Up to 4 years ]

Clinical benefit: confirmed complete response (CR) or partial response (PR) or had stable disease (SD) lasting at least 24 weeks. CR was the disappearance of all target lesions and nontarget 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. SD was having neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD).

• Original Primary Outcome Measures (submitted: June 28, 2007): Rate of adverse events and clinical benefit rate (complete response + partial response >= 24 weeks)

Current Secondary Outcome Measures (submitted: May 31, 2012)

• Progression-free Survival (PFS) [ Time Frame: Baseline Up to 4 years ]
  Median time from the date of enrollment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.
• Percentage of Participants With Objective Response [ Time Frame: Baseline Up to 4 years ]
  Percentage of participants with objective response based assessment of confirmed CR or confirmed PR according to Response Evaluation Criteria In Solid Tumors (RECIST). CR is disappearance of all target lesions. PR shows at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.
• Duration of Response [ Time Frame: Baseline Up to 4 years ]
  Time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or PD is objectively documented, taking as reference for PD the smallest sum longest diameters (LD) recorded since enrollment.
• Time to Treatment Failure (TTF) [ Time Frame: Baseline Up to 4 years ]
  TTF is defined as the time from the date of enrollment to the date of the first documentation of PD, the date of treatment discontinuation except completion of treatment, or date of death due to cancer.
• Overall Survival (OS) [ Time Frame: Baseline Until Death (Up to 4 years) ]
  Time in months from the date of enrollment to date of death due to any cause. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).

• Original Secondary Outcome Measures (submitted: June 28, 2007): Progression free survival, duration of response, overall survivial, pharmacokinetics

Current Other Pre-specified Outcome Measures (submitted: March 15, 2013)

• Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0 hours (pre-dose), 0.5 hours, 1, 2, 6, 24, 72, and 96 hours during Week 1 and 4 of treatment ]
  Sirolimus is a major metabolite of temsirolimus. As per planned analysis, only participants in "Temsirolimus 20 mg/m^2" treatment arm were to be drawn blood samples intensively for pharmacokinetic analysis.
• Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0 hours (pre-dose), 0.5, 1, 2, 6, 24, 72, and 96 hours during Week 1 and 4 of treatment ]
  Sirolimus is a major metabolite of temsirolimus. As per planned analysis, only participants in "Temsirolimus 20 mg/m^2" treatment arm were to be drawn blood samples intensively for pharmacokinetic analysis.
• Plasma Decay Half-Life (t1/2) [ Time Frame: 0 hours (pre-dose), 0.5, 1, 2, 6, 24, 72, and 96 hours during Week 1 and 4 of treatment ]
  Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Sirolimus is the major metabolite of temsirolimus. As per planned analysis, only participants in "Temsirolimus 20 mg/m^2" treatment arm were to be drawn blood samples intensively for pharmacokinetic analysis.
• Area Under the Concentration-Time Curve (AUC) [ Time Frame: 0 hours (pre-dose), 0.5 hours, 1, 2, 6, 24, 72, and 96 hours during Week 1 and 4 of treatment ]
  AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. Sirolimus is the major metabolite of temsirolimus. As per planned analysis, only participants in "Temsirolimus 20 mg/m^2" treatment arm were to be drawn blood samples intensively for pharmacokinetic analysis.
• Clearance (CLss) of Temsirolimus [ Time Frame: 0 hours (pre-dose), 0.5, 1, 2, 6, 24, 72, and 96 hours during Week 1 and 4 of treatment ]
  Steady state total body clearance equals infusion rate (zero order) divided by steady state plasma concentration of temsirolimus (R0/Css). As per planned analysis, only participants in "Temsirolimus 20 mg/m^2" treatment arm were to be drawn blood samples intensively for pharmacokinetic analysis.
• Volume of Distribution at Steady State (Vss) of Temsirolimus [ Time Frame: 0 hours (pre-dose), 0.5, 1, 2, 6, 24, 72, and 96 hours during Week 1 and 4 of treatment ]
  Vss is an estimate of the volume of distribution at steady state. It is used to predict the plasma concentrations following multiple dosing to a steady-state or pseudo-equilibrium. Vss is proportional to the amount of drug in the body versus the plasma concentration of the drug at steady state. As per planned analysis, only participants in "Temsirolimus 20 mg/m^2" treatment arm were to be drawn blood samples intensively for pharmacokinetic analysis.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Evaluating The Safety, Efficacy & Pharmacokinetics Of Temsirolimus(CCI-779) In Subjects With Advanced Renal Cell Carcinoma
• Official Title: Phase 2, Non Randomized, Open Label Study Of Temsirolimus (CCI-779) In Subjects With Advanced Renal Cell Carcinoma (RCC)
• Brief Summary: This is a study to evaluate the safety, efficacy and pharmacokinetics of temsirolimus in Asian patients with advanced renal cell carcinoma. The trial is only being conducted in Japan, Korea, and China.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Renal Cell Carcinoma

Intervention

• Drug: Temsirolimus (CCI-779)
  20 mg/m2 IV TEMSR weekly (Japan, n=6)
  Other Name: Torisel
• Drug: Temsirolimus (CCI-779)
  25 mg IV TEMSR weekly (all other pts)
  Other Name: Torisel

Study Arms

• Experimental: A.
  Intervention: Drug: Temsirolimus (CCI-779)
• Experimental: B.
  Intervention: Drug: Temsirolimus (CCI-779)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 14, 2011): 82
• Original Enrollment (submitted: June 28, 2007): 80
• Actual Study Completion Date: March 2012
• Actual Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subjects with histologically confirmed, advanced (stage IV or recurrent disease) RCC. The American Joint Committee on Cancer (AJCC) staging and classification criteria will be used.
• ECOG performance status of 0-1.
• At least one measurable lesion per RECIST.
• Age greater than or equal to 20 years.
• Japanese, Chinese, or Korean ethnicity.

Exclusion Criteria:

• CNS metastases at screening or history or CNS metastases.
• Prior targeted, chemotherapeutic, cytokine-based, or other investigational agents for the treatment of RCC within 4 weeks before first dose of test article. Subjects must have documented objective progressive disease after any prior systemic RCC treatment and have recovered to grade 1 or lower toxicities from effects of prior systemic therapy for RCC.
• In past 5 years, other prior malignancy (except basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 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: China, Japan, Korea, Republic of

Administrative Information

• NCT Number: NCT00494091
• Other Study ID Numbers: 3066K1-2217; B1771002
• Has Data Monitoring Committee: No
• 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: March 2013