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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01420081




Registration number
NCT01420081
Ethics application status
Date submitted
17/08/2011
Date registered
19/08/2011
Date last updated
8/01/2019

Titles & IDs
Public title
A Study Of Two Dual PI3K/mTOR Inhibitors, PF-04691502 And PF-05212384 In Patients With Recurrent Endometrial Cancer
Scientific title
A RANDOMIZED PHASE 2 NON-COMPARATIVE STUDY OF THE EFFICACY OF PF-04691502 AND PF-05212384 IN PATIENTS WITH RECURRENT ENDOMETRIAL CANCER
Secondary ID [1] 0 0
2011-003062-32
Secondary ID [2] 0 0
B1271004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endometrial Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PF-05212384
Treatment: Drugs - PF-05212384
Treatment: Drugs - PF-05212384

Experimental: B - PI3K Basal, IV Compound

Experimental: C - PI3K Activated, Oral Compound

Experimental: F - Japanese lead in cohort, IV compound


Treatment: Drugs: PF-05212384
154mg IV weekly

Treatment: Drugs: PF-05212384
154mg IV weekly

Treatment: Drugs: PF-05212384
154mg IV weekly

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
16 weeks from Cycle 1 Day 1
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
16 weeks from Cycle 1 Day 1
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Randomization to objective progression, death or last tumor assessment without progression (up to 12 months)
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Randomization to objective progression, death or last tumor assessment without progression (up to 12 months)
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
From Cycle 1 Day 1 to objective progressive disease or death due to any cause whichever occurs first (up to 12 months)
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
From Cycle 1 Day 1 to objective progressive disease or death due to any cause whichever occurs first (up to 12 months)
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
6 months
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
12 months
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
Baseline (Day -3) and Cycle1 to Cycle 3 where each cycle consist of 28 days
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
Baseline (Day -3) and Cycle1 to Cycle 3 where each cycle consist of 28 days
Secondary outcome [12] 0 0
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.
Timepoint [12] 0 0
Prior to Cycle 1 Day 1
Secondary outcome [13] 0 0
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.
Timepoint [13] 0 0
Baseline and Cycle1 to Cycle 5 where each cycle consist of 28 days
Secondary outcome [14] 0 0
Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinity (AUCinf) of PF-05212384 at Each Specified Time Points.
Timepoint [14] 0 0
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
Secondary outcome [15] 0 0
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.
Timepoint [15] 0 0
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
Secondary outcome [16] 0 0
Maximum Plasma Concentration (Cmax) of PF-05212384 at Each Specified Time Points.
Timepoint [16] 0 0
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
Secondary outcome [17] 0 0
Terminal Elimination Half Life (t½) of PF-05212384 at Each Specified Time Points.
Timepoint [17] 0 0
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
Secondary outcome [18] 0 0
Time for Cmax (Tmax) of PF-05212384 at Each Specified Time Points.
Timepoint [18] 0 0
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
Secondary outcome [19] 0 0
Clearance (CL) of PF-05212384 at Each Specified Time Points.
Timepoint [19] 0 0
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
Secondary outcome [20] 0 0
Steady State Volume of Distribution (Vss) of PF-05212384 at Each Specified Time Points.
Timepoint [20] 0 0
Pre-dose: 0 hours, and Post dose: 0.5 (after end of infusion), 1, 2, 4, 6, 24, 72, and 120 hours
Secondary outcome [21] 0 0
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.
Timepoint [21] 0 0
From baseline (-3 days) until 35 days post last dose
Secondary outcome [22] 0 0
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.
Timepoint [22] 0 0
From baseline (-3 days) until 35 days post last dose
Secondary outcome [23] 0 0
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.
Timepoint [23] 0 0
From baseline (-3 days) until 35 days post last dose
Secondary outcome [24] 0 0
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.
Timepoint [24] 0 0
From baseline (-3 days) until 35 days post last dose

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre, Division of Cancer Madicine - East Melbourne
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
New Mexico
Country [10] 0 0
Canada
State/province [10] 0 0
Alberta
Country [11] 0 0
Canada
State/province [11] 0 0
British Columbia
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
Japan
State/province [14] 0 0
Aichi
Country [15] 0 0
Japan
State/province [15] 0 0
Hyogo
Country [16] 0 0
Japan
State/province [16] 0 0
Saitama
Country [17] 0 0
Japan
State/province [17] 0 0
Tokyo
Country [18] 0 0
Poland
State/province [18] 0 0
Lodz
Country [19] 0 0
Poland
State/province [19] 0 0
Lublin
Country [20] 0 0
Russian Federation
State/province [20] 0 0
Stavropol Territory
Country [21] 0 0
Russian Federation
State/province [21] 0 0
Krasnodar
Country [22] 0 0
Russian Federation
State/province [22] 0 0
Pyatigorsk
Country [23] 0 0
Russian Federation
State/province [23] 0 0
Saint Petersburg
Country [24] 0 0
Spain
State/province [24] 0 0
Barcelona
Country [25] 0 0
Spain
State/province [25] 0 0
Madrid
Country [26] 0 0
Spain
State/province [26] 0 0
Valencia
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Surrey
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Glasgow
Country [29] 0 0
United Kingdom
State/province [29] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will investigate the individual safety and efficacy of two dual PI3K/mTOR
inhibitors in patients with recurrent endometrial cancer.
Trial website
https://clinicaltrials.gov/show/NCT01420081
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT01420081