Clinical Trial: A Study Of Two Dual PI3K/mTOR Inhibitors, PF-04691502 And PF-05212384 In Patients With Recurrent Endometrial Cancer

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Randomized Phase 2 Non-Comparative Study Of The Efficacy Of PF-04691502 And PF-05212384 In Patients With Recurrent Endometrial Cancer

Brief Summary: This study will investigate the individual safety and efficacy of two dual PI3K/mTOR inhibitors in patients with recurrent endometrial cancer.

Detailed Summary: The study was prematurely discontinued due to lack confidence in the Stathmin assay as a patient selection criteria and subsequent lack of confidence in the efficacy signal that was observed. The decision to terminate the study was made on January 23, 2014. It should be noted that safety concerns have not been seen in this study and have not factored into this decision.
Sponsor: Pfizer

Current Primary Outcome: Percentage of Participants With Clinical Benefit Response for PF-05212384 [ Time Frame: 16 weeks from Cycle 1 Day 1 ]

Clinical benefit response was defined as best overall response of complete response (CR), partial response (PR) or stable disease (SD) for at least 16 weeks from Cycle 1 Day 1 (C1D1) to the first time of disease progression. The primary analysis is based on the clinical benefit rate which is calculated as proportion of participants with a clinical benefit response relative to total number of response evaluable participants. Per RECIST v1.1 for target lesions: CR defined as disappearance of all target lesions; PR defined as >=30% decrease in the sum of the longest diameter of target lesions; SD does not qualify for CR, PR or Progression. All target lesions must be assessed. SD can follow PR only in the rare case that the sum increases by less than 20% from the nadir, but enough that a previously documented 30% decrease no longer holds. A Clopper-Pearson exact 95% CI for the clinical benefit rate is presented in the below table.


Original Primary Outcome: Clinical Benefit Rate [ Time Frame: 16 weeks ]

Current Secondary Outcome:

  • Clinical Benefit Response for PF-04691502 [ Time Frame: 16 weeks from Cycle 1 Day 1 ]
    Clinical benefit response was defined as best overall response of complete response (CR), partial response (PR) or stable disease (SD) for at least 16 weeks from Cycle 1 Day 1 (C1D1) to the first time of disease progression. The outcome data table below presents the number of participants with clinical benefit response as "yes" or "no". On 09 Oct 2012, Pfizer decided to stop enrollment into PF-04691502. While tumor assessment for PF-04691502 was included as a listing in the final report, formal efficacy analysis for PF-04691502 was not performed.
  • Percentage of Participants With Objective Response for PF-05212384 [ Time Frame: Randomization to objective progression, death or last tumor assessment without progression (up to 12 months) ]
    Objective response is defined as CR or PR. CR: Complete response: 2 or more objective statuses of CR a minimum of 4 weeks apart documented before PD. Partial response: 2 or more objective statuses of PR or better a minimum of 4 weeks apart documented before PD, but not qualifying as CR. Per RECIST v1.1 for target lesions: CR defined as disappearance of all target lesions; PR defined as >=30% decrease in the sum of the longest diameter of target lesions.
  • Objective Response for PF-04691502 [ Time Frame: Randomization to objective progression, death or last tumor assessment without progression (up to 12 months) ]
    Objective response is defined as CR or PR. CR: Complete response: 2 or more objective statuses of CR a minimum of 4 weeks apart documented before PD. Partial response: 2 or more objective statuses of PR or better a minimum of 4 weeks apart documented before PD, but not qualifying as CR. Per RECIST v1.1 for target lesions: CR defined as disappearance of all target lesions; PR defined as >=30% decrease in the sum of the longest diameter of target lesions. The outcome data table below presents the number of participants with objective response as "yes" or "no". On 09 Oct 2012, Pfizer decided to stop enrollment into PF-04691502. While tumor assessment for PF-04691502 was included as a listing in the final report, formal efficacy analysis for PF-04691502 was not performed.
  • Percentage of Participants With Progression Free Survival (PFS) at 6 Months for PF-05212384 [ Time Frame: 6 months ]
    Progression free survival is defined as the time from the date of cycle 1 day 1 to the date that objective progressive disease is documented or death due to any cause, whichever occurs first. PFS was characterized in terms of the probability of remaining progression-free at 6 months (based on Kaplan-Meier estimates). Progression is defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions with a minimum absolute increase of 5 mm, or an unequivocal progression of non-target lesion, or the appearance of new lesions.
  • Progression Free Survival for PF-05212384 [ Time Frame: From Cycle 1 Day 1 to objective progressive disease or death due to any cause whichever occurs first (up to 12 months) ]
    PFS is defined as the time from the date of cycle 1 day 1 to the date that objective progressive disease is documented or death due to any cause, whichever occurs first. PFS was characterized in terms of the median. Approximate 95% confidence interval corresponding to this estimate was computed. Progression is defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions with a minimum absolute increase of 5 mm, or an unequivocal progression of non-target lesion, or the appearance of new lesions.
  • Progression Free Survival for PF-04691502 [ Time Frame: From Cycle 1 Day 1 to objective progressive disease or death due to any cause whichever occurs first (up to 12 months) ]
    PFS is defined as the time from the date of cycle 1 day 1 to the date that objective progressive disease is documented or death due to any cause, whichever occurs first. PFS was characterized in terms of the median. Approximate 95% confidence interval corresponding to this estimate was computed. Progression is defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions with a minimum absolute increase of 5 mm, or an unequivocal progression of non-target lesion, or the appearance of new lesions. On 09 Oct 2012, Pfizer decided to stop enrollment into PF-04691502. While tumor assessment for PF-04691502 was included as a listing in the final report, formal efficacy analysis for PF-04691502 was not performed.
  • Overall Survival (OS) for PF-05212384 [ Time Frame: 12 months ]
    OS is defined as the time from the date of Cycle 1 Day 1 to the date of death.
  • Level of Each Pharmacodynamic Parameter at Specified Timepoints [ Time Frame: Baseline, Post-baseline ]
    PD biomarkers are measured at screening (baseline) and multiple time points post baseline. Baseline is defined as the last measurement prior to dosing, which is the measurement at screening or the cycle 1 day 1 pre-dose measurement if collected. This outcome measure will be updated once the

    Original Secondary Outcome:

    • Objective tumor response rate, as assessed using RECIST [ Time Frame: 12 months ]
    • Overall Survival [ Time Frame: 12 months ]
    • Progression Free Survival [ Time Frame: 12 months ]
    • Progression free survival rate at 6 months [ Time Frame: 6 months ]
    • Area under the plasma concentration versus time curve (AUC) of PF-04691502 [ Time Frame: Pre-dose, and post dose at 0.5, 1, 2, 3, 4, 6, and 24 hours post dose. Pre dose cycles 2, 3, 4 ]
    • Area under the plasma concentration versus time curve (AUC) of PF-05212384 [ Time Frame: 0, 0.5, 1, 2, 4, 6, 24, 72, and 120 hours post dose and pre and 0.5 hour post dose cycles 2, 3, 4 ]
    • Expression and/or phosphorylation in biopsied tumor tissue of PI3K pathway proteins [ Time Frame: Baseline and 28 days ]
    • Gene and/or protein expression biomarkers in biopsied tumor tissue relating to PI3K and/or mTOR pathway activation [ Time Frame: Baseline ]


    Information By: Pfizer

    Dates:
    Date Received: August 17, 2011
    Date Started: January 2012
    Date Completion:
    Last Updated: May 25, 2016
    Last Verified: May 2016