Temsirolimus With or Without Megestrol Acetate and Tamoxifen Citrate in Treating Patients With Advanced, Persistent, or Recurrent Endometrial Cancer
|Endometrial Carcinoma Recurrent Uterine Corpus Carcinoma Stage IIIA Uterine Corpus Cancer Stage IIIB Uterine Corpus Cancer Stage IIIC1 Uterine Corpus Cancer Stage IIIC2 Uterine Corpus Cancer Stage IVA Uterine Corpus Cancer Stage IVB Uterine Corpus Cancer||Other: Laboratory Biomarker Analysis Drug: Megestrol Acetate Drug: Tamoxifen Citrate Drug: Temsirolimus||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Randomized Phase II Trial of Temsirolimus (NCI-Supplied Agent, NSC # 683864) or the Combination of Hormonal Therapy Plus Temsirolimus in Women With Advanced, Persistent, or Recurrent Endometrial Carcinoma|
- Frequency of complete and partial clinical response, measured using GOG RECIST Criteria [ Time Frame: Up to 1 year ]
- Progression-free survival (PFS) [ Time Frame: From study entry until disease progression, death or date of last contact, assessed up to 1 year ]PFS time distributions will be estimated.
- Survival time [ Time Frame: From entry into the study to death or the date of last contact, assessed up to 1 year ]Survival time distributions will be estimated.
- Incidence of adverse events defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease that occurs in a patient administered a medical treatment, whether the event is considered related [ Time Frame: Up to 1 year ]The frequency and severity of all toxicities will be tabulated.
- Changes in levels of expression of the candidate markers [ Time Frame: Baseline to up to 1 year ]The levels of expression of the candidate markers measured prior to study treatment will be tabulated/described. Methods such as logistic or proportional hazards regression will likely be used for these analyses when response, PFS or survival is the dependent variable when necessary model assumptions are appropriate. Exploratory analyses utilizing methods appropriate to the type of data will be conducted to examine the associations between markers and between markers and clinical characteristics.
|Study Start Date:||September 2008|
|Study Completion Date:||February 2017|
|Primary Completion Date:||February 2017 (Final data collection date for primary outcome measure)|
Experimental: Arm I (temsirolimus)
Patients receive temsirolimus IV over 30 minutes once weekly for 6 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Temsirolimus
Experimental: Arm II (temsirolimus, megestrol acetate, tamoxifen citrate)
Patients receive temsirolimus as in Arm I and megestrol acetate PO BID for 3 weeks alternating with tamoxifen citrate PO BID for 3 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Megestrol Acetate
Other Names:Drug: Tamoxifen Citrate
Other Names:Drug: Temsirolimus
I. To determine the response rate of patients with advanced, persistent, or recurrent endometrial cancer when treated with each of the arms of the trial; the proposed arms are: Arm #1 temsirolimus intravenously (IV) weekly, Arm #2 megestrol (megestrol acetate)/tamoxifen (tamoxifen citrate) plus temsirolimus IV weekly.
II. Time to progression and number of patients remaining on study therapy at 24 weeks.
I. To describe the toxicities of each of the arms of the trial when used for patients with advanced/metastatic endometrial cancer.
I. Explore whether immunohistochemical expression of hormone receptors (estrogen receptor-alpha, estrogen receptor-beta, progesterone receptors-A, progesterone receptor-B and the alternative estrogen receptor, G protein-coupled estrogen receptor [GPR]-30) or components of the mammalian target of rapamycin (mTOR) signaling pathway (normal and mutant phosphatase and tensin homolog [PTEN], total and phosphorylated v-akt murine thymoma viral oncogene homolog 1 [Akt] as well as total and phosphorylated p70S6 kinase) are associated with treatment, outcome or clinical characteristics.
II. Explore whether single nucleotide polymorphisms (SNPs) in the FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1) and regulatory associated protein of mTOR (RAPTOR) genes, mutations in phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), PTEN and paxillin or copy number abnormalities in PTEN and paxillin are associated with treatment, outcome or clinical characteristics.
OUTLINE: Patients are randomized to 1 of 2 treatment arms. (Closed to accrual as of 11/22/2010)
ARM I: Patients receive temsirolimus IV over 30 minutes once weekly for 6 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
ARM II (Closed to accrual as of 12/21/2009): Patients receive temsirolimus as in Arm I and megestrol acetate orally (PO) twice daily (BID) for 3 weeks alternating with tamoxifen citrate PO BID for 3 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 1 year.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00729586
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|Principal Investigator:||Gini Fleming||NRG Oncology|