Endometrial NeoplasmsPhase 2NCT01420081
A Study Of Two Dual PI3K/mTOR Inhibitors, PF-04691502 And PF-05212384 In Patients With Recurrent Endometrial Cancer
A Phase 2 study testing PF-05212384 in people with Endometrial Neoplasms, run by Pfizer at 51 sites in 8 countries.
Trial summary
This study will investigate the individual safety and efficacy of two dual PI3K/mTOR inhibitors in patients with recurrent endometrial cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Endometrial Neoplasms
- What is being tested?
- PF-05212384
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 51 sitesin 8 countries
- Study dates
- 19 Jan 2012to 25 Dec 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
51 sites in 8 countries.
51 sites in 8 countries
United States21 sites
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
University of Michigan
Ann Arbor, Michigan, 48109
University of Alabama at Birmingham
Birmingham, Alabama, 35233
University of Alabama at Birmingham, IDS Pharmacy
Birmingham, Alabama, 35249
University of Alabama at Birmingham
Birmingham, Alabama, 35249
Massachusetts General Hospital
Boston, Massachusetts, 02114
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
University of Chicago Medical Center
Chicago, Illinois, 60637
Mary Bird Perkins Cancer Center at St. Tammany Parish Hospital
Covington, Louisiana, 70433
Women's Cancer Care
Covington, Louisiana, 70433
University of Kansas
Fairway, Kansas, 66205
University of Kansas Hospital
Kansas City, Kansas, 66160
University of California Medical Center
La Jolla, California, 92037
Moores UC San Diego Cancer Center
La Jolla, California, 92093
Women's Cancer Care
Metairie, Louisiana, 70006
Mercy Hospital
Miami, Florida, 33133
Mercy Research Institute
Miami, Florida, 33133
University of Chicago Medicine Comprehensive Cancer Center at Silver Cross Hospital
New Lenox, Illinois, 60451
University of California Medical Center
San Diego, California, 92103
University of Kansas Cancer Center and Medical Pavilion
Westwood, Kansas, 66205
Canada8 sites
Foothills Medical Center
Calgary, Alberta, T2N 2T9
Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, K7L 5P9
Royal Victoria Hospital
Montreal, Quebec, H3A 1A1
Jewish General Hospital
Montreal, Quebec, H3T 1E2
St. Mary's Hospital
Montreal, Quebec, H3T 1M5
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
British Columbia Cancer Agency - Vancouver Centre
Vancouver, British Columbia, V5Z 4E6
Spain6 sites
Hospital Universitari Vall d'hebron
Barcelona, 08035
Centro Oncologico MD Anderson Internacional España
Madrid, 28033
Hospital Clinico San Carlos
Madrid, 28040
Hospital Universitario La Paz
Madrid, 28046
Fundacion Instituto Valenciano de Oncologia - I.V.O.
Valencia, 46009
Fundacion Instituto Valenciano de Oncologia - I.V.O
Valencia, 46009
Japan4 sites
Hyogo Cancer Center
Akashi, Hyōgo, 673-8558
National Cancer Center Hospital
Chuo-Ku, Tokyo, 104-0045
Saitama Medical University International Medical Center
Hidaka, Saitama, 350-1298
Aichi cancer center hospital
Nagoya, Aichi-ken, 464-8681
Russia4 sites
Clinical Oncology Dispensary 1 of Department of Healthcare of the Krasnodar Region
Krasnodar, 350040
Federal State Healthcare Institution
Lermontov, Stavropol Territory, 357340
Pyatigorsk Oncology Center
Pyatigorsk, 357502
Saint Petersburg State Healthcare Institution City Clinical Oncology Dispensary
Saint Petersburg, 198255
United Kingdom4 sites
Beatson Oncology Centre
Glasgow, G12 0YN
University College London Hospital NHS Foundation Trust
London, NW1 2PG
The Royal Marsden NHS Foundation Trust
London, SW3 6JJ
The Royal Marsden NHS Foundation Trust
Sutton, Surrey, SM2 5PT
Poland3 sites
Regionalny Osrodek Onkologiczny Wojewodzki Szpital Specjalistyczny im. M. Kopernika
Lodz, 93-509
Zaklad Radiologii
Lodz, 93-513
Centrum Onkologii Ziemi Lubelskiej im. Św. Jana z Dukli
Lublin, 20-090
Australia1 site
Peter MacCallum Cancer Centre, Division of Cancer Madicine
East Melbourne, Victoria, 3002
About this study
Official title: 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.
Read the 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.
- Conditions
- Endometrial Neoplasms
- Being tested
- PF-05212384
- Keywords
- uterine neoplasms, endometrial, uterine, cancer, PI3K, mTOR, PI3K/mTOR, recurrent, metastatic
- Medical subject headings
- Endometrial Neoplasms, Uterine Neoplasms, Neoplasms, Recurrence, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-05212384Drug
Also called PKI-587
154mg IV weekly
PF-05212384Drug
Also called PKI-587
154mg IV weekly
PF-05212384Drug
Also called PKI-587
154mg IV weekly
| Study group | Role | What they receive |
|---|---|---|
| B | Experimental | PI3K Basal, IV Compound Receives: Drug: PF-05212384 |
| C | Experimental | PI3K Activated, Oral Compound Receives: Drug: PF-05212384 |
| F | Experimental | Japanese lead in cohort, IV compound Receives: Drug: PF-05212384 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 16 weeks from Cycle 1 Day 1
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.
Measured: 16 weeks from Cycle 1 Day 1
Secondary outcomes (24)
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.
Measured: Randomization to objective progression, death or last tumor assessment without progression (up to 12 months)
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.
Measured: Randomization to objective progression, death or last tumor assessment without progression (up to 12 months)
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.
Measured: From Cycle 1 Day 1 to objective progressive disease or death due to any cause whichever occurs first (up to 12 months)
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.
Measured: From Cycle 1 Day 1 to objective progressive disease or death due to any cause whichever occurs first (up to 12 months)
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.
Measured: 6 months
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.
Measured: 12 months
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.
Measured: Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days
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.
Measured: Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days
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.
Measured: Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days
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.
Measured: Baseline (Day -3) and Cycle1 to Cycle 3 where each cycle consist of 28 days
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.
Measured: Baseline (Day -3) and Cycle1 to Cycle 3 where each cycle consist of 28 days
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.
Measured: Prior to Cycle 1 Day 1
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.
Measured: Baseline and Cycle1 to Cycle 5 where each cycle consist of 28 days
Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinity (AUCinf) of PF-05212384 at Each Specified Time Points.
Measured: 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
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.
Measured: 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
Maximum Plasma Concentration (Cmax) of PF-05212384 at Each Specified Time Points.
Measured: 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
Terminal Elimination Half Life (t½) of PF-05212384 at Each Specified Time Points.
Measured: 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
Time for Cmax (Tmax) of PF-05212384 at Each Specified Time Points.
Measured: 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
Clearance (CL) of PF-05212384 at Each Specified Time Points.
Measured: 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
Steady State Volume of Distribution (Vss) of PF-05212384 at Each Specified Time Points.
Measured: Pre-dose: 0 hours, and Post dose: 0.5 (after end of infusion), 1, 2, 4, 6, 24, 72, and 120 hours
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.
Measured: From baseline (-3 days) until 35 days post last dose
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.
Measured: From baseline (-3 days) until 35 days post last dose
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.
Measured: From baseline (-3 days) until 35 days post last dose
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.
Measured: From baseline (-3 days) until 35 days post last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2011 (estimated)
- Study start19 Jan 2012
- Primary completion30 Apr 2014
- Study completion25 Dec 2015
Why it stopped: See termination reason in detailed description.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Endometrial NeoplasmsStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01420081
- Sponsor's protocol ID
- B1271004
- Other IDs
- 2011-003062-32
- Status last verified
- Dec 2018
- First submitted
- 17 Aug 2011
- Last updated
- 8 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 27103175
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A RANDOMIZED PHASE 2 NON-COMPARATIVE STUDY OF THE EFFICACY OF PF-04691502 AND PF-05212384 IN PATIENTS WITH RECURRENT ENDOMETRIAL CANCER
- ClinicalTrials.gov ID
- NCT01420081
- Acronym / sponsor ID
- B1271004
- Conditions
- Endometrial Neoplasms
- Keywords
- uterine neoplasms, endometrial, uterine, cancer, PI3K, mTOR, PI3K/mTOR, recurrent
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: See termination reason in detailed description.
- Enrolment
- 67 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 19 Jan 2012 (actual)
- Primary completion
- 30 Apr 2014 (actual)
- Study completion
- 25 Dec 2015 (actual)
- First posted
- 19 Aug 2011 (estimated)
- Results
- Posted 19 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| B | Experimental | Drug: PF-05212384PI3K Basal, IV Compound |
| C | Experimental | Drug: PF-05212384PI3K Activated, Oral Compound |
| F | Experimental | Drug: PF-05212384Japanese lead in cohort, IV compound |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PF-05212384Also: PKI-587154mg IV weekly | Drug | B |
| PF-05212384Also: PKI-587154mg IV weekly | Drug | C |
| PF-05212384Also: PKI-587154mg IV weekly | Drug | F |
Primary 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 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.
24 secondary outcomes
Objective Response for PF-04691502
Time frame: Randomization to objective progression, death or last tumor assessment without progression (up to 12 months)
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)
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)
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)
Percentage of Participants With Progression Free Survival (PFS) at 6 Months for PF-05212384
Time frame: 6 months
Overall Survival (OS) for PF-05212384
Time frame: 12 months
Level of Each Pharmacodynamic Parameter at Specified Timepoints- Glucose (mg/dL)
Time frame: Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days
Level of Each Pharmacodynamic Parameter at Specified Timepoints- Insulin (UIU/mL)
Time frame: Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days
Level of Each Pharmacodynamic Parameter at Specified Timepoints- Glycosylated Hemoglobin (HbA1c)
Time frame: Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days
Level of Each Pharmacodynamic Parameter at Specified Timepoints- Cholesterol (mg/dL)
Time frame: Baseline (Day -3) and Cycle1 to Cycle 3 where each cycle consist of 28 days
Level of Each Pharmacodynamic Parameter at Specified Timepoints- Triglycerides (mg/dL)
Time frame: Baseline (Day -3) and Cycle1 to Cycle 3 where each cycle consist of 28 days
Stathmin H Score [Mean (SD)] for Each Treatment Arm With Gene and/or Protein Expression Biomarkers in Biopsied Tumor Tissue
Time frame: Prior to Cycle 1 Day 1
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.
Time frame: Baseline and Cycle1 to Cycle 5 where each cycle consist of 28 days
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
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
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
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
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
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
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
Number of Treatment-emergent Adverse Events (TEAEs) - All Causalities
Time frame: From baseline (-3 days) until 35 days post last dose
Summary of Treatment-emergent Adverse Events (TEAEs) - All Causalities
Time frame: From baseline (-3 days) until 35 days post last dose
Number of Treatment-related TEAEs
Time frame: From baseline (-3 days) until 35 days post last dose
Summary of Treatment-related TEAEs
Time frame: From baseline (-3 days) until 35 days post last dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27103175Del 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.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
51 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PF-05212384 in people with Endometrial Neoplasms, run by Pfizer at 51 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 51 sites in United States, Canada, Spain, Japan, Russia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Benefit Response for PF-04691502 (time frame: 16 weeks from Cycle 1 Day 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01420081, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2019.