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

Sponsor

MedSIR (Other)

Overall Status

Completed

CT.gov ID

NCT02093598

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

3.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Endometrioid mTOR Protein	Drug: Temsirolimus	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Study Start Date :

May 1, 2012

Actual Primary Completion Date :

Mar 1, 2014

Actual Study Completion Date :

Mar 1, 2014

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

To evaluate the mTOR inhibitor effects of temsirolimus directly on endometrial tumor tissue after four weeks of therapy. [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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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