Trial record 1 of 1 for:    B1271004
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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: June 3, 2015
Last verified: June 2015
Results First Received: April 30, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Endometrial Neoplasms
Intervention: Drug: PF-05212384

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
An open-label, Phase 2, four-arm, non-comparative study to assess the safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of PF-04691502 (an oral PI3K/mTOR inhibitor) and PF-05212384 (an Intravenous [IV] Phosphoinositide 3-Kinase [PI3K]/Mammalian Target of Rapamycin [mTOR] inhibitor).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
This study was conducted in parallel-arms in adult participants with recurrent endometrial cancer. Randomized arms included PF-05212384 (154mg dosage) and PF-04691502 (8mg which was lowered to 6mg) for both PI3K Basal or Activated. Lead-in Cohorts included PF-05212384 (89mg or 154mg) and PF-04691502 (4mg).

Reporting Groups
  Description
PF-04691502 8 mg (PI3K Basal) Eligible participants were categorized by PI3K pathway activation status (i.e. PI3K basal). Participants self-administered PF-04691502 8 mg orally, once daily (QD) until they experienced unacceptable toxicity, disease progression, significant deviation, withdrawal of consent or death. Dose of the participants were reduced to 6 mg if they were on 8 mg dose.
PF-04691502 6 mg (PI3K Basal) Eligible participants were categorized by PI3K pathway activation status (i.e. PI3K basal). Participants self-administered PF-04691502 6 mg orally, QD until they experienced unacceptable toxicity, disease progression, significant deviation, withdrawal of consent or death.
PF-04691502 8 mg (PI3K Activated) Eligible participants were categorized by PI3K pathway activation status (i.e. PI3K activated). Participants self-administered PF-04691502 8 mg orally, QD until they experienced unacceptable toxicity, disease progression, significant deviation, withdrawal of consent or death. Dose of the participants were reduced to 6 mg if they were on 8 mg dose.
PF-04691502 6 mg (PI3K Activated) Eligible participants were categorized by PI3K pathway activation status (i.e. PI3K activated). Participants self-administered PF-04691502 6 mg orally, QD until they experienced unacceptable toxicity, disease progression, significant deviation, withdrawal of consent or death.
PF-05212384 154 mg (PI3K Basal) Eligible participants were categorized by PI3K pathway activation status (i.e. PI3K basal). Participants received PF-05212384 154 mg by 30 minute infusion at the study site, once weekly (Quaque, QW) until they experienced unacceptable toxicity, disease progression, significant deviation, withdrawal of consent or death.
PF-05212384 154 mg (PI3K Activated) Eligible participants were categorized by PI3K pathway activation status (i.e. PI3K activated). Participants received PF-05212384 154 mg by 30 minute infusion at the study site, QW until they experienced unacceptable toxicity, disease progression, significant deviation, withdrawal of consent or death.
Lead-in-cohort (LIC) PF-04691502 (4 mg) Participants who were enrolled in the PF-04691502 LIC began dosing with PF-04691502 4 mg at least 4 days (but no more than 10 days) prior to Cycle 1 Day 1 and continued taking PF-05691502 until they experienced unacceptable toxicity, disease progression, significant deviation, withdrawal of consent or death.
LIC PF-05212384 (89 mg) Participants who were enrolled in the PF-05212384 LIC began dosing with PF-05212384 89 mg at least 4 days (but no more than 10 days) prior to Cycle 1 Day 1 and continued taking PF-05212384 until they experienced unacceptable toxicity, disease progression, significant deviation, withdrawal of consent or death.
LIC PF-05212384 (154 mg) Participants who were enrolled in the PF-05212384 LIC began dosing with PF-05212384 154 mg at least 4 days (but no more than 10 days) prior to Cycle 1 Day 1 and continued taking PF-05212384 until they experienced unacceptable toxicity, disease progression, significant deviation, withdrawal of consent or death.

Participant Flow:   Overall Study
    PF-04691502 8 mg (PI3K Basal)     PF-04691502 6 mg (PI3K Basal)     PF-04691502 8 mg (PI3K Activated)     PF-04691502 6 mg (PI3K Activated)     PF-05212384 154 mg (PI3K Basal)     PF-05212384 154 mg (PI3K Activated)     Lead-in-cohort (LIC) PF-04691502 (4 mg)     LIC PF-05212384 (89 mg)     LIC PF-05212384 (154 mg)  
STARTED     3     1     11     3     20     20     3     3     3  
COMPLETED     0     0     0     0     0     0     0     0     0  
NOT COMPLETED     3     1     11     3     20     20     3     3     3  
Death                 1                 0                 8                 0                 7                 12                 0                 1                 1  
Lost to Follow-up                 0                 0                 0                 0                 1                 1                 0                 0                 0  
Study Terminated by Sponsor                 2                 1                 1                 3                 9                 6                 3                 2                 2  
Subject Refused Futher Follow-up                 0                 0                 1                 0                 1                 0                 0                 0                 0  
Other Reasons                 0                 0                 1                 0                 0                 0                 0                 0                 0  
Ongoing at data cut off                 0                 0                 0                 0                 2                 1                 0                 0                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
PF-04691502 8 mg (PI3K Basal) Eligible participants were categorized by PI3K pathway activation status (i.e. PI3K basal). Participants self-administered PF-04691502 8 mg orally, QD until they experienced unacceptable toxicity, disease progression, significant deviation, withdrawal of consent or death. Dose of the participants were reduced to 6 mg if they were on 8 mg dose.
PF-04691502 6 mg (PI3K Basal) Eligible participants were categorized by PI3K pathway activation status (i.e. PI3K basal). Participants self-administered PF-04691502 6 mg orally, QD until they experienced unacceptable toxicity, disease progression, significant deviation, withdrawal of consent or death.
PF-04691502 8 mg (PI3K Activated) Eligible participants were categorized by PI3K pathway activation status (i.e. PI3K activated). Participants self-administered PF-04691502 8 mg orally, QD until they experienced unacceptable toxicity, disease progression, significant deviation, withdrawal of consent or death. Dose of the participants were reduced to 6 mg if they were on 8 mg dose.
PF-04691502 6 mg (PI3K Activated) Eligible participants were categorized by PI3K pathway activation status (i.e. PI3K activated). Participants self-administered PF-04691502 6 mg orally, QD until they experienced unacceptable toxicity, disease progression, significant deviation, withdrawal of consent or death.
PF-05212384 154 mg (PI3K Basal) Eligible participants were categorized by PI3K pathway activation status (i.e. PI3K basal). Participants received PF-05212384 154 mg by 30 minute infusion at the study site, QW until they experienced unacceptable toxicity, disease progression, significant deviation, withdrawal of consent or death.
PF-05212384 154 mg (PI3K Activated) Eligible participants were categorized by PI3K pathway activation status (i.e. PI3K activated). Participants received PF-05212384 154 mg by 30 minute infusion at the study site, QW until they experienced unacceptable toxicity, disease progression, significant deviation, withdrawal of consent or death.
Lead-in-cohort (LIC) PF-04691502 (4 mg) Participants who were enrolled in the PF-04691502 LIC began dosing with PF-04691502 4 mg at least 4 days (but no more than 10 days) prior to Cycle 1 Day 1 and continued taking PF-05691502 until they experienced unacceptable toxicity, disease progression, significant deviation, withdrawal of consent or death.
LIC PF-05212384 (89 mg) Participants who were enrolled in the PF-05212384 LIC began dosing with PF-05212384 89 mg at least 4 days (but no more than 10 days) prior to Cycle 1 Day 1 and continued taking PF-05212384 until they experienced unacceptable toxicity, disease progression, significant deviation, withdrawal of consent or death.
LIC PF-05212384 (154 mg) Participants who were enrolled in the PF-05212384 LIC began dosing with PF-05212384 154 mg at least 4 days (but no more than 10 days) prior to Cycle 1 Day 1 and continued taking PF-05212384 until they experienced unacceptable toxicity, disease progression, significant deviation, withdrawal of consent or death.
Total Total of all reporting groups

Baseline Measures
    PF-04691502 8 mg (PI3K Basal)     PF-04691502 6 mg (PI3K Basal)     PF-04691502 8 mg (PI3K Activated)     PF-04691502 6 mg (PI3K Activated)     PF-05212384 154 mg (PI3K Basal)     PF-05212384 154 mg (PI3K Activated)     Lead-in-cohort (LIC) PF-04691502 (4 mg)     LIC PF-05212384 (89 mg)     LIC PF-05212384 (154 mg)     Total  
Number of Participants  
[units: participants]
  3     1     11     3     20     20     3     3     3     67  
Age, Customized  
[units: participants]
                   
< 18 years     0     0     0     0     0     0     0     0     0     0  
18 - 44 years     0     0     0     0     0     0     0     1     0     1  
45 - 64 years     2     1     4     3     9     4     2     1     2     28  
>= 65 years     1     0     7     0     11     16     1     1     1     38  
Gender  
[units: participants]
                   
Female     3     1     11     3     20     20     3     3     3     67  
Male     0     0     0     0     0     0     0     0     0     0  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants With Clinical Benefit Response   [ Time Frame: 16 weeks from Cycle 1 Day 1 ]

2.  Secondary:   Percentage of Participants With Objective Response   [ Time Frame: Randomization to objective progression, death or last tumor assessment without progression (up to 12 months) ]

3.  Secondary:   Overall Survival (OS)   [ Time Frame: 12 months ]

4.  Secondary:   Percentage of Participants With Progression Free Survival (PFS) at 6 Months   [ Time Frame: 6 months ]

5.  Secondary:   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) ]

6.  Secondary:   Level of Each Pharmacodynamic Parameter at Specified Timepoints   [ Time Frame: Baseline, Post-baseline ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

7.  Secondary:   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 ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

8.  Secondary:   Percentage of Participants in Each Treatment Arm With Gene and/or Protein Expression Biomarkers in Biopsied Tumor Tissue   [ Time Frame: Baseline, Post-baseline ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

9.  Secondary:   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 ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
On 09Oct12, Pfizer decided to discontinue clinical development of PF-04691502 and stop participants enrollment in this arm. Hence limited primary and secondary endpoints summaries were performed in this arm and no efficacy endpoints were evaluated.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com


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: June 3, 2015
Health Authority: United States: Food and Drug Administration