Trial record 1 of 1 for:    B1271004
Previous Study | Return to List | Next Study

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

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01420081
First received: August 17, 2011
Last updated: June 3, 2015
Last verified: June 2015

August 17, 2011
June 3, 2015
January 2012
April 2014   (final data collection date for primary outcome measure)
Percentage of Participants With Clinical Benefit Response [ Time Frame: 16 weeks from Cycle 1 Day 1 ] [ Designated as safety issue: No ]
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 the proportion of participants with a clinical benefit response relative to the total number of response evaluable participants. Per Response Evaluation Criteria In Solid Tumors Criteria (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.
Clinical Benefit Rate [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01420081 on ClinicalTrials.gov Archive Site
  • Percentage of Participants With Objective Response [ Time Frame: Randomization to objective progression, death or last tumor assessment without progression (up to 12 months) ] [ Designated as safety issue: No ]
    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.
  • Overall Survival (OS) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    OS is defined as the time from the date of Cycle 1 Day 1 to the date of death.
  • Percentage of Participants With Progression Free Survival (PFS) at 6 Months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: From Cycle 1 Day 1 to objective progressive disease or death due to any cause whichever occurs first (up to 12 months) ] [ Designated as safety issue: No ]
    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.
  • Level of Each Pharmacodynamic Parameter at Specified Timepoints [ Time Frame: Baseline, Post-baseline ] [ Designated as safety issue: No ]
    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 data is available with the supplemental clinical study report.
  • Percentage of Participants in Each Treatment Arm With Expression and/or Phosphorylation in PI3K Pathway Proteins in Biopsied Tumor Tissue [ Time Frame: Baseline, Post-baseline ] [ Designated as safety issue: No ]
    Expression and/or phosphorylation in biopsied tumor tissue of PI3K pathway proteins such as p-AKT, p-S6, p-S6K, p-mTOR, p-PRAS40, stathmin were to be assessed. This outcome measure will be updated once the data is available with the supplemental clinical study report.
  • Percentage of Participants in Each Treatment Arm With Gene and/or Protein Expression Biomarkers in Biopsied Tumor Tissue [ Time Frame: Baseline, Post-baseline ] [ Designated as safety issue: No ]
    Gene and/or protein expression biomarkers in biopsied tumor tissue relating to PI3K and/or mTOR pathway activation, such as PIK3CA and PIK3R1 mutations, PTEN protein levels, and PIK3CA gene amplification were to be assessed. This outcome measure will be updated once the data is available with the supplemental clinical study report.
  • Pharmacokinetic Parameters of PF-04691502 and PF-05212384 at Each Specified Time Points [ 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 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters were to be evaluated at each specified time points. This outcome measure will be updated once the data is available with the supplemental clinical study report.
  • Objective tumor response rate, as assessed using RECIST [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Progression Free Survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Progression free survival rate at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Expression and/or phosphorylation in biopsied tumor tissue of PI3K pathway proteins [ Time Frame: Baseline and 28 days ] [ Designated as safety issue: No ]
  • Gene and/or protein expression biomarkers in biopsied tumor tissue relating to PI3K and/or mTOR pathway activation [ Time Frame: Baseline ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study Of Two Dual PI3K/mTOR Inhibitors, PF-04691502 And PF-05212384 In Patients With Recurrent Endometrial Cancer
A Randomized Phase 2 Non-comparative Study Of The Efficacy Of Pf-04691502 And Pf-05212384 In Patients With Recurrent Endometrial Cancer

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

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Endometrial Neoplasms
Drug: PF-05212384
154mg IV weekly
Other Name: PKI-587
  • Experimental: B
    PI3K Basal, IV Compound
    Intervention: Drug: PF-05212384
  • Experimental: C
    PI3K Activated, Oral Compound
    Intervention: Drug: PF-05212384
  • Experimental: F
    Japanese lead in cohort, IV compound
    Intervention: Drug: PF-05212384
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
67
December 2015
April 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Recurrent endometrial carcinoma
  • Disease progression following one or two lines of prior treatment with platinum containing chemotherapy
  • Tumor tissue available at time of screening for PI3K analysis
  • Adequate performance status
  • Adequate glucose control, bone marrow, kidney, liver, and heart function

Exclusion Criteria:

  • More than 2 prior cytotoxic chemo regimens for endometrial carcinoma
  • Prior therapy with an agent known to be a PI3K, and or mTOR and or AKT inhibitor
  • Active brain metastases
Female
20 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   Japan,   Poland,   Russian Federation,   Spain,   United Kingdom
Slovakia,   Germany
 
NCT01420081
B1271004, 2011-003062-32
No
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP