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

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01420081
First received: August 17, 2011
Last updated: April 30, 2015
Last verified: April 2015
  Purpose

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


Condition Intervention Phase
Endometrial Neoplasms
Drug: PF-05212384
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase 2 Non-comparative Study Of The Efficacy Of Pf-04691502 And Pf-05212384 In Patients With Recurrent Endometrial Cancer

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Percentage of Participants With Clinical Benefit Response [ Time Frame: 16 weeks from Cycle 1 Day 1 ] [ Designated as safety issue: No ]
    Clinical benefit response was defined as best overall response of complete response (CR), partial response (PR) or stable disease (SD) for at least 16 weeks from Cycle 1 Day 1 (C1D1) to the first time of disease progression. The primary analysis is based on the clinical benefit rate which is calculated as the proportion of participants with a clinical benefit response relative to the total number of response evaluable participants. A Clopper-Pearson exact 95% CI for the clinical benefit rate is presented in the below table.


Secondary Outcome Measures:
  • Percentage of Participants With Objective Response [ Time Frame: Randomization to objective progression, death or last tumor assessment without progression (up to 12 months) ] [ Designated as safety issue: No ]
    Objective response is defined as CR or PR. CR: Complete response: 2 or more objective statuses of CR a minimum of 4 weeks apart documented before PD. Partial response: 2 or more objective statuses of PR or better a minimum of 4 weeks apart documented before PD, but not qualifying as CR.

  • Overall Survival (OS) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    OS is defined as the time from the date of Cycle 1 Day 1 to the date of death.

  • Percentage of Participants With Progression Free Survival (PFS) at 6 Months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Progression free survival is defined as the time from the date of cycle 1 day 1 to the date that objective progressive disease is documented or death due to any cause, whichever occurs first. PFS was characterized in terms of the probability of remaining progression-free at 6 months (based on Kaplan-Meier estimates). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions with a minimum absolute increase of 5 mm, or an unequivocal progression of non-target lesion, or the appearance of new lesions.

  • Progression Free Survival [ Time Frame: From Cycle 1 Day 1 to objective progressive disease or death due to any cause whichever occurs first (up to 12 months) ] [ Designated as safety issue: No ]
    PFS is defined as the time from the date of cycle 1 day 1 to the date that objective progressive disease is documented or death due to any cause, whichever occurs first. PFS was characterized in terms of the median. Approximate 95% confidence interval corresponding to this estimate was computed. Progression is defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions with a minimum absolute increase of 5 mm, or an unequivocal progression of non-target lesion, or the appearance of new lesions.

  • Level of Each Pharmacodynamic Parameter at Specified Timepoints [ Time Frame: Baseline, Post-baseline ] [ Designated as safety issue: No ]
    PD biomarkers are measured at screening (baseline) and multiple time points post baseline. Baseline is defined as the last measurement prior to dosing, which is the measurement at screening or the C1D1 pre-dose measurement if collected. This outcome measure will be updated once the data is available with the supplemental clinical study report.

  • Percentage of Participants in Each Treatment Arm With Expression and/or Phosphorylation in PI3K Pathway Proteins in Biopsied Tumor Tissue [ Time Frame: Baseline, Post-baseline ] [ Designated as safety issue: No ]
    Expression and/or phosphorylation in biopsied tumor tissue of PI3K pathway proteins such as p-AKT, p-S6, p-S6K, p-mTOR, p-PRAS40, stathmin were to be assessed. This outcome measure will be updated once the data is available with the supplemental clinical study report.

  • Percentage of Participants in Each Treatment Arm With Gene and/or Protein Expression Biomarkers in Biopsied Tumor Tissue [ Time Frame: Baseline, Post-baseline ] [ Designated as safety issue: No ]
    Gene and/or protein expression biomarkers in biopsied tumor tissue relating to PI3K and/or mTOR pathway activation, such as PIK3CA and PIK3R1 mutations, PTEN protein levels, and PIK3CA gene amplification were to be assessed. This outcome measure will be updated once the data is available with the supplemental clinical study report.

  • Pharmacokinetic Parameters of PF-04691502 and PF-05212384 at Each Specified Time Points [ Time Frame: 0, 0.5, 1, 2, 4, 6, 24, 72, and 120 hours post dose and pre and 0.5 hour post dose cycles 2, 3, 4 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters were to be evaluated at each specified time points. This outcome measure will be updated once the data is available with the supplemental clinical study report.


Enrollment: 67
Study Start Date: January 2012
Estimated Study Completion Date: December 2015
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: B
PI3K Basal, IV Compound
Drug: PF-05212384
154mg IV weekly
Other Name: PKI-587
Experimental: C
PI3K Activated, Oral Compound
Drug: PF-05212384
154mg IV weekly
Other Name: PKI-587
Experimental: F
Japanese lead in cohort, IV compound
Drug: PF-05212384
154mg IV weekly
Other Name: PKI-587

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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01420081

  Show 48 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01420081     History of Changes
Other Study ID Numbers: B1271004, 2011-003062-32
Study First Received: August 17, 2011
Results First Received: April 30, 2015
Last Updated: April 30, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
uterine neoplasms
endometrial
uterine
cancer
PI3K
mTOR
PI3K/mTOR
recurrent
metastatic

Additional relevant MeSH terms:
Endometrial Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Site
Urogenital Neoplasms
Uterine Diseases
Uterine Neoplasms

ClinicalTrials.gov processed this record on May 21, 2015