Back to resultsA Study Of Two Dual PI3K/mTOR Inhibitors, PF-04691502 And PF-05212384 In Patients With Recurrent Endometrial Cancer
Primary Purpose
Endometrial Neoplasms
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
PF-05212384
PF-05212384
PF-05212384
Sponsored by
About this trial
This is an interventional treatment trial for Endometrial Neoplasms focused on measuring uterine neoplasms, endometrial, uterine, cancer, PI3K, mTOR, PI3K/mTOR, recurrent, metastatic
Eligibility Criteria
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
Sites / Locations
- University of Alabama at Birmingham
- University of Alabama at Birmingham, IDS Pharmacy
- University of Alabama at Birmingham
- University of California Medical Center
- Moores UC San Diego Cancer Center
- University of California Medical Center
- Mercy Hospital
- Mercy Research Institute
- University of Chicago Medical Center
- University of Chicago Medicine Comprehensive Cancer Center at Silver Cross Hospital
- University of Kansas
- University of Kansas Hospital
- University of Kansas Cancer Center and Medical Pavilion
- Mary Bird Perkins Cancer Center at St. Tammany Parish Hospital
- Women's Cancer Care
- Women's Cancer Care
- Massachusetts General Hospital
- Brigham and Women's Hospital
- Dana Farber Cancer Institute
- University of Michigan
- University of New Mexico Cancer Center
- Peter MacCallum Cancer Centre, Division of Cancer Madicine
- Foothills Medical Center
- Tom Baker Cancer Centre
- British Columbia Cancer Agency - Vancouver Centre
- Cancer Centre of Southeastern Ontario at Kingston General Hospital
- Princess Margaret Hospital
- Royal Victoria Hospital
- Jewish General Hospital
- St. Mary's Hospital
- Aichi cancer center hospital
- Hyogo Cancer Center
- Saitama Medical University International Medical Center
- National Cancer Center Hospital
- Regionalny Osrodek Onkologiczny Wojewodzki Szpital Specjalistyczny im. M. Kopernika
- Zaklad Radiologii
- Centrum Onkologii Ziemi Lubelskiej im. Św. Jana z Dukli
- Federal State Healthcare Institution
- Clinical Oncology Dispensary 1 of Department of Healthcare of the Krasnodar Region
- Pyatigorsk Oncology Center
- Saint Petersburg State Healthcare Institution City Clinical Oncology Dispensary
- Hospital Universitari Vall d'hebron
- Centro Oncologico MD Anderson Internacional España
- Hospital Clinico San Carlos
- Hospital Universitario La Paz
- Fundacion Instituto Valenciano de Oncologia - I.V.O.
- Fundacion Instituto Valenciano de Oncologia - I.V.O
- The Royal Marsden NHS Foundation Trust
- Beatson Oncology Centre
- University College London Hospital NHS Foundation Trust
- The Royal Marsden NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
B
C
F
Arm Description
PI3K Basal, IV Compound
PI3K Activated, Oral Compound
Japanese lead in cohort, IV compound
Outcomes
Primary Outcome Measures
Clinical Benefit Response for PF-04691502
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 Clinical Benefit Response for PF-05212384
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.
Secondary Outcome Measures
Objective Response for PF-04691502
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 Objective Response for PF-05212384
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.
Progression Free Survival for PF-04691502
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.
Progression Free Survival for PF-05212384
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.
Percentage of Participants With Progression Free Survival (PFS) at 6 Months for PF-05212384
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.
Overall Survival (OS) for PF-05212384
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- Glucose (mg/dL)
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.
Level of Each Pharmacodynamic Parameter at Specified Timepoints- Insulin (UIU/mL)
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.
Level of Each Pharmacodynamic Parameter at Specified Timepoints- Glycosylated Hemoglobin (HbA1c)
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.
Level of Each Pharmacodynamic Parameter at Specified Timepoints- Cholesterol (mg/dL)
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.
Level of Each Pharmacodynamic Parameter at Specified Timepoints- Triglycerides (mg/dL)
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.
Stathmin H Score [Mean (SD)] for Each Treatment Arm With Gene and/or Protein Expression Biomarkers in Biopsied Tumor Tissue
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.
Each slide was imaged by whole slide scanning and patient samples were scored as follows:
Pathologist manual score (0, 1+, 2+, 3+) for overall staining intensity of tumor tissue.
Percentage of positive tumor cells staining at 0, 1+, 2+, and 3+.
H-score value (integer between 0 and 300) for tumor cell staining was calculated. The higher the stathmin staining, the higher the stathmin H-score.
Percentage of Participants in Each Treatment Arm With Gene and/or Protein Expression Biomarkers- PIK3CA Amplification, KRAS Mutation P/N, KRAS Mutation OBSV, PTEN Stroma Manual Score, PTEN Tumor Manual Score, KRAS SCC and Stathmin H/L,Tissue.
Gene and/or protein expression biomarkers in biopsied tumor tissue relating to PI3K and/or mTOR pathway activation, such as PIK3CA and PIK3R1 mutations, Phosphatase And Tensin Homolog (PTEN) protein levels, and PIK3CA gene amplification were to be assessed.
Stained tissues were evaluated by a board-certified pathologist who provided a manual pathology score (i.e., 0, 1+, 2+, or 3+) and, if appropriate, comments upon the staining of the specimen.
The directionality increases from 0 to 3+ with 0 being no staining for PTEN by IHC and 3+ being high staining intensity for PTEN.
Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinity (AUCinf) of PF-05212384 at Each Specified Time Points.
Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-05212384 at Each Specified Time Points.
Maximum Plasma Concentration (Cmax) of PF-05212384 at Each Specified Time Points.
Terminal Elimination Half Life (t½) of PF-05212384 at Each Specified Time Points.
Time for Cmax (Tmax) of PF-05212384 at Each Specified Time Points.
Clearance (CL) of PF-05212384 at Each Specified Time Points.
Steady State Volume of Distribution (Vss) of PF-05212384 at Each Specified Time Points.
Number of Treatment-emergent Adverse Events (TEAEs) - All Causalities
Safety of participants in terms of TEAEs. Note: One subject treated with PF-05212384 had the stathmin status changed after randomization and was categorized under the corresponding arm.
Summary of Treatment-emergent Adverse Events (TEAEs) - All Causalities
Safety of participants in terms of TEAEs. Note: One subject treated with PF-05212384 had the stathmin status changed after randomization and was categorized under the corresponding arm.
Number of Treatment-related TEAEs
Safety of subject in terms of number of participants with treatment related AEs.
Note: One subject treated with PF-05212384 had the stathmin status changed after randomization and was categorized under the corresponding arm.
Summary of Treatment-related TEAEs
Safety of subject in terms of number of participants with treatment related AEs.
Note: One subject treated with PF-05212384 had the stathmin status changed after randomization and was categorized under the corresponding arm.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01420081
Brief Title
A Study Of Two Dual PI3K/mTOR Inhibitors, PF-04691502 And PF-05212384 In Patients With Recurrent Endometrial Cancer
Official Title
A RANDOMIZED PHASE 2 NON-COMPARATIVE STUDY OF THE EFFICACY OF PF-04691502 AND PF-05212384 IN PATIENTS WITH RECURRENT ENDOMETRIAL CANCER
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Terminated
Why Stopped
See termination reason in detailed description.
Study Start Date
January 19, 2012 (Actual)
Primary Completion Date
April 30, 2014 (Actual)
Study Completion Date
December 25, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will investigate the individual safety and efficacy of two dual PI3K/mTOR inhibitors in patients with recurrent endometrial cancer.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Endometrial Neoplasms
Keywords
uterine neoplasms, endometrial, uterine, cancer, PI3K, mTOR, PI3K/mTOR, recurrent, metastatic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
67 (Actual)
8. Arms, Groups, and Interventions
Arm Title
B
Arm Type
Experimental
Arm Description
PI3K Basal, IV Compound
Arm Title
C
Arm Type
Experimental
Arm Description
PI3K Activated, Oral Compound
Arm Title
F
Arm Type
Experimental
Arm Description
Japanese lead in cohort, IV compound
Intervention Type
Drug
Intervention Name(s)
PF-05212384
Other Intervention Name(s)
PKI-587
Intervention Description
154mg IV weekly
Intervention Type
Drug
Intervention Name(s)
PF-05212384
Other Intervention Name(s)
PKI-587
Intervention Description
154mg IV weekly
Intervention Type
Drug
Intervention Name(s)
PF-05212384
Other Intervention Name(s)
PKI-587
Intervention Description
154mg IV weekly
Primary Outcome Measure Information:
Title
Clinical Benefit Response for PF-04691502
Description
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.
Time Frame
16 weeks from Cycle 1 Day 1
Title
Percentage of Participants With Clinical Benefit Response for PF-05212384
Description
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.
Time Frame
16 weeks from Cycle 1 Day 1
Secondary Outcome Measure Information:
Title
Objective Response for PF-04691502
Description
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.
Time Frame
Randomization to objective progression, death or last tumor assessment without progression (up to 12 months)
Title
Percentage of Participants With Objective Response for PF-05212384
Description
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.
Time Frame
Randomization to objective progression, death or last tumor assessment without progression (up to 12 months)
Title
Progression Free Survival for PF-04691502
Description
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.
Time Frame
From Cycle 1 Day 1 to objective progressive disease or death due to any cause whichever occurs first (up to 12 months)
Title
Progression Free Survival for PF-05212384
Description
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.
Time Frame
From Cycle 1 Day 1 to objective progressive disease or death due to any cause whichever occurs first (up to 12 months)
Title
Percentage of Participants With Progression Free Survival (PFS) at 6 Months for PF-05212384
Description
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.
Time Frame
6 months
Title
Overall Survival (OS) for PF-05212384
Description
OS is defined as the time from the date of Cycle 1 Day 1 to the date of death.
Time Frame
12 months
Title
Level of Each Pharmacodynamic Parameter at Specified Timepoints- Glucose (mg/dL)
Description
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.
Time Frame
Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days
Title
Level of Each Pharmacodynamic Parameter at Specified Timepoints- Insulin (UIU/mL)
Description
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.
Time Frame
Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days
Title
Level of Each Pharmacodynamic Parameter at Specified Timepoints- Glycosylated Hemoglobin (HbA1c)
Description
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.
Time Frame
Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days
Title
Level of Each Pharmacodynamic Parameter at Specified Timepoints- Cholesterol (mg/dL)
Description
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.
Time Frame
Baseline (Day -3) and Cycle1 to Cycle 3 where each cycle consist of 28 days
Title
Level of Each Pharmacodynamic Parameter at Specified Timepoints- Triglycerides (mg/dL)
Description
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.
Time Frame
Baseline (Day -3) and Cycle1 to Cycle 3 where each cycle consist of 28 days
Title
Stathmin H Score [Mean (SD)] for Each Treatment Arm With Gene and/or Protein Expression Biomarkers in Biopsied Tumor Tissue
Description
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.
Each slide was imaged by whole slide scanning and patient samples were scored as follows:
Pathologist manual score (0, 1+, 2+, 3+) for overall staining intensity of tumor tissue.
Percentage of positive tumor cells staining at 0, 1+, 2+, and 3+.
H-score value (integer between 0 and 300) for tumor cell staining was calculated. The higher the stathmin staining, the higher the stathmin H-score.
Time Frame
Prior to Cycle 1 Day 1
Title
Percentage of Participants in Each Treatment Arm With Gene and/or Protein Expression Biomarkers- PIK3CA Amplification, KRAS Mutation P/N, KRAS Mutation OBSV, PTEN Stroma Manual Score, PTEN Tumor Manual Score, KRAS SCC and Stathmin H/L,Tissue.
Description
Gene and/or protein expression biomarkers in biopsied tumor tissue relating to PI3K and/or mTOR pathway activation, such as PIK3CA and PIK3R1 mutations, Phosphatase And Tensin Homolog (PTEN) protein levels, and PIK3CA gene amplification were to be assessed.
Stained tissues were evaluated by a board-certified pathologist who provided a manual pathology score (i.e., 0, 1+, 2+, or 3+) and, if appropriate, comments upon the staining of the specimen.
The directionality increases from 0 to 3+ with 0 being no staining for PTEN by IHC and 3+ being high staining intensity for PTEN.
Time Frame
Baseline and Cycle1 to Cycle 5 where each cycle consist of 28 days
Title
Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinity (AUCinf) of PF-05212384 at Each Specified Time Points.
Time Frame
Pre-dose: 0 hours, and Post dose: 0.5 (after end of infusion), 1, 2, 4, 6, 24, 72, and 120 hours at Day 1
Title
Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-05212384 at Each Specified Time Points.
Time Frame
Pre-dose: 0 hours, and Post dose: 0.5 (after end of infusion), 1, 2, 4, 6, 24, 72, and 120 hours at Day 1
Title
Maximum Plasma Concentration (Cmax) of PF-05212384 at Each Specified Time Points.
Time Frame
Pre-dose: 0 hours, and Post dose: 0.5 (after end of infusion), 1, 2, 4, 6, 24, 72, and 120 hours at Day 1
Title
Terminal Elimination Half Life (t½) of PF-05212384 at Each Specified Time Points.
Time Frame
Pre-dose: 0 hours, and Post dose: 0.5 (after end of infusion), 1, 2, 4, 6, 24, 72, and 120 hours at Day 1
Title
Time for Cmax (Tmax) of PF-05212384 at Each Specified Time Points.
Time Frame
Pre-dose: 0 hours, and Post dose: 0.5 (after end of infusion), 1, 2, 4, 6, 24, 72, and 120 hours at Day 1
Title
Clearance (CL) of PF-05212384 at Each Specified Time Points.
Time Frame
Pre-dose: 0 hours, and Post dose: 0.5 (after end of infusion), 1, 2, 4, 6, 24, 72, and 120 hours at Day 1
Title
Steady State Volume of Distribution (Vss) of PF-05212384 at Each Specified Time Points.
Time Frame
Pre-dose: 0 hours, and Post dose: 0.5 (after end of infusion), 1, 2, 4, 6, 24, 72, and 120 hours
Title
Number of Treatment-emergent Adverse Events (TEAEs) - All Causalities
Description
Safety of participants in terms of TEAEs. Note: One subject treated with PF-05212384 had the stathmin status changed after randomization and was categorized under the corresponding arm.
Time Frame
From baseline (-3 days) until 35 days post last dose
Title
Summary of Treatment-emergent Adverse Events (TEAEs) - All Causalities
Description
Safety of participants in terms of TEAEs. Note: One subject treated with PF-05212384 had the stathmin status changed after randomization and was categorized under the corresponding arm.
Time Frame
From baseline (-3 days) until 35 days post last dose
Title
Number of Treatment-related TEAEs
Description
Safety of subject in terms of number of participants with treatment related AEs.
Note: One subject treated with PF-05212384 had the stathmin status changed after randomization and was categorized under the corresponding arm.
Time Frame
From baseline (-3 days) until 35 days post last dose
Title
Summary of Treatment-related TEAEs
Description
Safety of subject in terms of number of participants with treatment related AEs.
Note: One subject treated with PF-05212384 had the stathmin status changed after randomization and was categorized under the corresponding arm.
Time Frame
From baseline (-3 days) until 35 days post last dose
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
University of Alabama at Birmingham, IDS Pharmacy
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35249
Country
United States
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35249
Country
United States
Facility Name
University of California Medical Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Moores UC San Diego Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
University of California Medical Center
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Mercy Hospital
City
Miami
State/Province
Florida
ZIP/Postal Code
33133
Country
United States
Facility Name
Mercy Research Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33133
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
University of Chicago Medicine Comprehensive Cancer Center at Silver Cross Hospital
City
New Lenox
State/Province
Illinois
ZIP/Postal Code
60451
Country
United States
Facility Name
University of Kansas
City
Fairway
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
University of Kansas Hospital
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
University of Kansas Cancer Center and Medical Pavilion
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Mary Bird Perkins Cancer Center at St. Tammany Parish Hospital
City
Covington
State/Province
Louisiana
ZIP/Postal Code
70433
Country
United States
Facility Name
Women's Cancer Care
City
Covington
State/Province
Louisiana
ZIP/Postal Code
70433
Country
United States
Facility Name
Women's Cancer Care
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70006
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
University of New Mexico Cancer Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Name
Peter MacCallum Cancer Centre, Division of Cancer Madicine
City
East Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
Facility Name
Foothills Medical Center
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 2T9
Country
Canada
Facility Name
Tom Baker Cancer Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
British Columbia Cancer Agency - Vancouver Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
Cancer Centre of Southeastern Ontario at Kingston General Hospital
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 5P9
Country
Canada
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Royal Victoria Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3A 1A1
Country
Canada
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
St. Mary's Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1M5
Country
Canada
Facility Name
Aichi cancer center hospital
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
464-8681
Country
Japan
Facility Name
Hyogo Cancer Center
City
Akashi
State/Province
Hyogo
ZIP/Postal Code
673-8558
Country
Japan
Facility Name
Saitama Medical University International Medical Center
City
Hidaka
State/Province
Saitama
ZIP/Postal Code
350-1298
Country
Japan
Facility Name
National Cancer Center Hospital
City
Chuo-Ku
State/Province
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
Facility Name
Regionalny Osrodek Onkologiczny Wojewodzki Szpital Specjalistyczny im. M. Kopernika
City
Lodz
ZIP/Postal Code
93-509
Country
Poland
Facility Name
Zaklad Radiologii
City
Lodz
ZIP/Postal Code
93-513
Country
Poland
Facility Name
Centrum Onkologii Ziemi Lubelskiej im. Św. Jana z Dukli
City
Lublin
ZIP/Postal Code
20-090
Country
Poland
Facility Name
Federal State Healthcare Institution
City
Lermontov
State/Province
Stavropol Territory
ZIP/Postal Code
357340
Country
Russian Federation
Facility Name
Clinical Oncology Dispensary 1 of Department of Healthcare of the Krasnodar Region
City
Krasnodar
ZIP/Postal Code
350040
Country
Russian Federation
Facility Name
Pyatigorsk Oncology Center
City
Pyatigorsk
ZIP/Postal Code
357502
Country
Russian Federation
Facility Name
Saint Petersburg State Healthcare Institution City Clinical Oncology Dispensary
City
Saint Petersburg
ZIP/Postal Code
198255
Country
Russian Federation
Facility Name
Hospital Universitari Vall d'hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Centro Oncologico MD Anderson Internacional España
City
Madrid
ZIP/Postal Code
28033
Country
Spain
Facility Name
Hospital Clinico San Carlos
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Fundacion Instituto Valenciano de Oncologia - I.V.O.
City
Valencia
ZIP/Postal Code
46009
Country
Spain
Facility Name
Fundacion Instituto Valenciano de Oncologia - I.V.O
City
Valencia
ZIP/Postal Code
46009
Country
Spain
Facility Name
The Royal Marsden NHS Foundation Trust
City
Sutton
State/Province
Surrey
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
Facility Name
Beatson Oncology Centre
City
Glasgow
ZIP/Postal Code
G12 0YN
Country
United Kingdom
Facility Name
University College London Hospital NHS Foundation Trust
City
London
ZIP/Postal Code
NW1 2PG
Country
United Kingdom
Facility Name
The Royal Marsden NHS Foundation Trust
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Citations:
PubMed Identifier
27103175
Citation
Del Campo JM, Birrer M, Davis C, Fujiwara K, Gollerkeri A, Gore M, Houk B, Lau S, Poveda A, Gonzalez-Martin A, Muller C, Muro K, Pierce K, Suzuki M, Vermette J, Oza A. A randomized phase II non-comparative study of PF-04691502 and gedatolisib (PF-05212384) in patients with recurrent endometrial cancer. Gynecol Oncol. 2016 Jul;142(1):62-69. doi: 10.1016/j.ygyno.2016.04.019. Epub 2016 Apr 24.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B1271004&StudyName=A%20Study%20Of%20two%20dual%20PI3K/mTOR%20inhibitors%2C%20PF-04691502%20And%20PF-05212384%20In%20Patients%20With%20Recurrent%20Endometrial%20Cancer
Description
To obtain contact information for a study center near you, click here.
Learn more about this trial
A Study Of Two Dual PI3K/mTOR Inhibitors, PF-04691502 And PF-05212384 In Patients With Recurrent Endometrial Cancer
We'll reach out to this number within 24 hrs