Clinical trial NCT01420081: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Endometrial Neoplasms
Keywords: uterine neoplasms
endometrial
uterine
cancer
PI3K
mTOR
PI3K/mTOR
recurrent
metastatic
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-08-19
Enrollment: 67
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Clinical Benefit Response for PF-04691502
timeFrame: 16 weeks from Cycle 1 Day 1
measure: Percentage of Participants With Clinical Benefit Response for PF-05212384
timeFrame: 16 weeks from Cycle 1 Day 1
Secondary outcomes:
measure: Objective Response for PF-04691502
timeFrame: Randomization to objective progression, death or last tumor assessment without progression (up to 12 months)
measure: Percentage of Participants With Objective Response for PF-05212384
timeFrame: Randomization to objective progression, death or last tumor assessment without progression (up to 12 months)
measure: Progression Free Survival for PF-04691502
timeFrame: From Cycle 1 Day 1 to objective progressive disease or death due to any cause whichever occurs first (up to 12 months)
measure: Progression Free Survival for PF-05212384
timeFrame: From Cycle 1 Day 1 to objective progressive disease or death due to any cause whichever occurs first (up to 12 months)
measure: Percentage of Participants With Progression Free Survival (PFS) at 6 Months for PF-05212384
timeFrame: 6 months
measure: Overall Survival (OS) for PF-05212384
timeFrame: 12 months
measure: Level of Each Pharmacodynamic Parameter at Specified Timepoints- Glucose (mg/dL)
timeFrame: Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days
measure: Level of Each Pharmacodynamic Parameter at Specified Timepoints- Insulin (UIU/mL)
timeFrame: Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days
measure: Level of Each Pharmacodynamic Parameter at Specified Timepoints- Glycosylated Hemoglobin (HbA1c)
timeFrame: Baseline (Day -3) and Cycle1 to Cycle 5 where each cycle consist of 28 days
measure: Level of Each Pharmacodynamic Parameter at Specified Timepoints- Cholesterol (mg/dL)
timeFrame: Baseline (Day -3) and Cycle1 to Cycle 3 where each cycle consist of 28 days
measure: Level of Each Pharmacodynamic Parameter at Specified Timepoints- Triglycerides (mg/dL)
timeFrame: Baseline (Day -3) and Cycle1 to Cycle 3 where each cycle consist of 28 days
measure: Stathmin H Score [Mean (SD)] for Each Treatment Arm With Gene and/or Protein Expression Biomarkers in Biopsied Tumor Tissue
timeFrame: Prior to Cycle 1 Day 1
measure: 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.
timeFrame: Baseline and Cycle1 to Cycle 5 where each cycle consist of 28 days
measure: Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinity (AUCinf) of PF-05212384 at Each Specified Time Points.
timeFrame: 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
measure: 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.
timeFrame: 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
measure: Maximum Plasma Concentration (Cmax) of PF-05212384 at Each Specified Time Points.
timeFrame: 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
measure: Terminal Elimination Half Life (t½) of PF-05212384 at Each Specified Time Points.
timeFrame: 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
measure: Time for Cmax (Tmax) of PF-05212384 at Each Specified Time Points.
timeFrame: 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
measure: Clearance (CL) of PF-05212384 at Each Specified Time Points.
timeFrame: 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
measure: Steady State Volume of Distribution (Vss) of PF-05212384 at Each Specified Time Points.
timeFrame: Pre-dose: 0 hours, and Post dose: 0.5 (after end of infusion), 1, 2, 4, 6, 24, 72, and 120 hours
measure: Number of Treatment-emergent Adverse Events (TEAEs) - All Causalities
timeFrame: From baseline (-3 days) until 35 days post last dose
measure: Summary of Treatment-emergent Adverse Events (TEAEs) - All Causalities
timeFrame: From baseline (-3 days) until 35 days post last dose
measure: Number of Treatment-related TEAEs
timeFrame: From baseline (-3 days) until 35 days post last dose
measure: Summary of Treatment-related TEAEs
timeFrame: From baseline (-3 days) until 35 days post last dose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham, IDS Pharmacy
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: La Jolla
country: United States
facility: University of California Medical Center
state: California
city: La Jolla
country: United States
facility: Moores UC San Diego Cancer Center
state: California
city: San Diego
country: United States
facility: University of California Medical Center
state: California
city: Miami
country: United States
facility: Mercy Hospital
state: Florida
city: Miami
country: United States
facility: Mercy Research Institute
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: New Lenox
country: United States
facility: University of Chicago Medicine Comprehensive Cancer Center at Silver Cross Hospital
state: Illinois
city: Fairway
country: United States
facility: University of Kansas
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Westwood
country: United States
facility: University of Kansas Cancer Center and Medical Pavilion
state: Kansas
city: Covington
country: United States
facility: Mary Bird Perkins Cancer Center at St. Tammany Parish Hospital
state: Louisiana
city: Covington
country: United States
facility: Women's Cancer Care
state: Louisiana
city: Metairie
country: United States
facility: Women's Cancer Care
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre, Division of Cancer Madicine
state: Victoria
city: Calgary
country: Canada
facility: Foothills Medical Center
state: Alberta
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency - Vancouver Centre
state: British Columbia
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Royal Victoria Hospital
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: St. Mary's Hospital
state: Quebec
city: Nagoya
country: Japan
facility: Aichi cancer center hospital
state: Aichi
city: Akashi
country: Japan
facility: Hyogo Cancer Center
state: Hyogo
city: Hidaka
country: Japan
facility: Saitama Medical University International Medical Center
state: Saitama
city: Chuo-Ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Lodz
country: Poland
facility: Regionalny Osrodek Onkologiczny Wojewodzki Szpital Specjalistyczny im. M. Kopernika
city: Lodz
country: Poland
facility: Zaklad Radiologii
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej im. Św. Jana z Dukli
city: Lermontov
country: Russian Federation
facility: Federal State Healthcare Institution
state: Stavropol Territory
city: Krasnodar
country: Russian Federation
facility: Clinical Oncology Dispensary 1 of Department of Healthcare of the Krasnodar Region
city: Pyatigorsk
country: Russian Federation
facility: Pyatigorsk Oncology Center
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg State Healthcare Institution City Clinical Oncology Dispensary
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'hebron
city: Madrid
country: Spain
facility: Centro Oncologico MD Anderson Internacional España
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Valencia
country: Spain
facility: Fundacion Instituto Valenciano de Oncologia - I.V.O.
city: Valencia
country: Spain
facility: Fundacion Instituto Valenciano de Oncologia - I.V.O
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
state: Surrey
city: Glasgow
country: United Kingdom
facility: Beatson Oncology Centre
city: London
country: United Kingdom
facility: University College London Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
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.