POEM STUDY: A Phase IIa Trial in Endometrial Carcinoma With Temsirolimus (POEM)

November 25, 2020 updated by: MedSIR

"A Phase IIa Pharmacokinetic-pharmacodynamic Study to Confirm the Inhibitory Effect of Temsirolimus, Targeting the mTOR Pathway in Endometrial Carcinoma"

Type of Application: Clinical trial of new indication.

Experimental drug: The study dose of temsirolimus will be 25 mg administered intravenously, infused over a 30- to 60-minute period once weekly for 28 days (Total doses: 4 doses). Temsirolimus is a selective inhibitor of mTOR (mammalian target of rapamycin). Pharmacotherapeutic group: Protein Kinase Inhibitors; ATC code: L01X E09.

Primary Objective:

  • To identify in tumor samples future biomarkers associated with a short term exposure to temsirolimus.
  • This is an exploratory clinical study. No efficacy objectives are included in this clinical trial.

Secondary Objectives:

  • To estimate the tolerability for all temsirolimus-treated patients throughout the study and up to 28 days after the last dose of temsirolimus.
  • To correlate observed changes with the different type of endometrial carcinoma (type I and type II), with regard to proteins related to mTOR (p4EBP1, pS6K1, c-MYC, cyclin D, p27, BAD, p53, Bcl-2 PTEN, pAKT, mTOR),
  • To estimate the potential predictive value of some biomarkers (immunostaining for PTEN, pAKT, mTOR), relevant mutations in PTEN, PI3KCA, k-RAS, CTNNB1, and microsatellite instability status.
  • To estimate the prognostic value of Ki67 expression after short-term presurgical therapy exposure
  • To collect data about the differences in expression profile, assessed by RNA microarrays

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain
      • Madrid, Spain
      • Valencia, Spain

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients must have histologically-confirmed endometrial cancer
  2. Stage I - II (grade 1, 2 or 3), candidates for surgery as the primary treatment
  3. Age ≥ 18 years
  4. WHO performance status ≤ 2
  5. Adequate bone marrow function
  6. Adequate liver function
  7. Adequate renal function
  8. Fasting serum cholesterol ≤300 mg/dL or ≤7.75 mmol/L and fasting triglycerides ≤ 2.5 x ULN
  9. Signed informed consent

Exclusion Criteria:

  1. Subjects who have received prior anticancer therapies for the current endometrial cancer
  2. Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery or patients that may require major surgery during the course of the study
  3. Prior treatment with any investigational drug within the preceding 4 weeks
  4. Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent
  5. Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period
  6. Uncontrolled brain or leptomeningeal metastases
  7. Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin
  8. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
  9. Patients with an active, bleeding diathesis
  10. Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods
  11. Patients who have received prior treatment with an mTOR inhibitor
  12. Patients with a known hypersensitivity to rapamycine derivates or to its excipients
  13. History of noncompliance to medical regimens
  14. Patients unwilling to or unable to comply with the study protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Temsirolimus
25 mg administered intravenously, infused over a 30- to 60-minute period once weekly for 28 days (Total doses: 4 doses).
Drug: Temsirolimus
Other Names:
  • Torisel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate the mTOR inhibitor effects of temsirolimus directly on endometrial tumor tissue after four weeks of therapy.
Time Frame: 1 month after last dose of the last patient
To evaluate the mTOR inhibitor effects, assessed by level 4EBP1 and S6K1, of temsirolimus directly on endometrial tumor tissue after four weeks of therapy.
1 month after last dose of the last patient

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate if mTOR inhibition is associated with changes in tumor-tissue
Time Frame: 1 month after the surgery of the last patient

To evaluate if mTOR inhibition is associated with changes in tumor-tissue:

  • Signal transduction: AKT and PTEN
  • c-MYC, cyclin D activity
  • Proliferation index analysis: p53, p27, BAD, Bcl-2 and ki-67
1 month after the surgery of the last patient

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

MedSIR

Investigators

  • Principal Investigator: Andrés Poveda, Oncologist, Valencia, Spain

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2012

Primary Completion (Actual)

March 1, 2014

Study Completion (Actual)

March 1, 2014

Study Registration Dates

First Submitted

February 11, 2014

First Submitted That Met QC Criteria

March 20, 2014

First Posted (Estimate)

March 21, 2014

Study Record Updates

Last Update Posted (Actual)

November 27, 2020

Last Update Submitted That Met QC Criteria

November 25, 2020

Last Verified

March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LLO-TEM-2011-01/TEM IIG-4
  • 2011-005031-96 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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