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

NCT02093598 | Completed Phase 2

• 2 other identifiers: LLO-TEM-2011-01/TEM IIG-42011-005031-96
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

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

Conditions

Carcinoma, Endometrioid; mTOR Protein

Keywords

pharmacokinetic; pharmacodynamic; Carcinoma, Endometrioid; mTOR protein; temsirolimus; torisel; biological marker; phase II

Outcome Measures

Primary Outcomes (1)

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

  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 Outcomes (1)

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

  1 month after the surgery of the last patient

Study Arms (1)

Temsirolimus

EXPERIMENTAL

25 mg administered intravenously, infused over a 30- to 60-minute period once weekly for 28 days (Total doses: 4 doses).

Drug: Temsirolimus

Interventions

Temsirolimus DRUG

Also known as: Torisel

Temsirolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• MedSIR: lead

Study Sites (3)

Unknown Facility

Barcelona, Spain

Location

Unknown Facility

Madrid, Spain

Location

Unknown Facility

Valencia, Spain

Location

MeSH Terms

Conditions

Carcinoma, Endometrioid

Interventions

temsirolimus

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Endometrial Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Ovarian Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Study Officials

• Andrés Poveda, Oncologist

  Valencia, Spain

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2014
• First Posted: March 21, 2014
• Study Start: May 1, 2012
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: November 27, 2020

Record last verified: 2014-03

Locations

ES (3)