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: August 7, 2014
Last verified: August 2014
  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:
  • Number of Participants With Clinical Benefit Response (CBR) [ Time Frame: 16 ] [ Designated as safety issue: No ]
    CR+PR+SD 16 weeks


Secondary Outcome Measures:
  • Number of Participants With Objective Response [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.

  • Overall Survival (OS) [ Time Frame: 12.0 ] [ Designated as safety issue: No ]
  • Progression-Free Survival (PFS) [ Time Frame: 12 ] [ Designated as safety issue: No ]
    Median time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. PFS calculated as (Weeks) = (first event date minus first dose date plus 1) divided by 7

  • Progression-Free Survival (PFS) [ Time Frame: 6 ] [ Designated as safety issue: No ]
    Median time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. PFS calculated as (Weeks) = (first event date minus first dose date plus 1) divided by 7

  • Area under the Concentration-Time Curve (AUC) [ Time Frame: Pre-dose, and post dose at 0.5, 1, 2, 3, 4, 6, and 24 hours post dose. Pre dose cycles 2, 3, 4 ] [ Designated as safety issue: No ]
    AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.

  • Area under the Concentration-Time Curve (AUC) [ 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 ]
    AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.

  • Expression and/or phosphorylation in biopsied tumor tissue of PI3K pathway proteins [ Time Frame: Baseline and 28 days ] [ Designated as safety issue: No ]
  • Gene and/or protein expression biomarkers in biopsied tumor tissue relating to PI3K and/or mTOR pathway activation [ Time Frame: Baseline ] [ Designated as safety issue: No ]

Enrollment: 67
Study Start Date: January 2012
Estimated Study Completion Date: December 2014
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 51 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
Study First Received: August 17, 2011
Last Updated: August 7, 2014
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:
Neoplasms
Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female

ClinicalTrials.gov processed this record on August 26, 2014