This randomized phase II trial studies how well temsirolimus with or without megestrol acetate and tamoxifen citrate works in treating patients with endometrial cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment, has returned after a period of improvement, or is persistent. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of endometrial cancer cells. Hormone therapy using megestrol acetate and tamoxifen citrate may fight endometrial cancer by blocking the use of estrogen by the tumor cells. It is not yet known whether temsirolimus is more effective when given alone or together with megestrol acetate and tamoxifen citrate in treating endometrial cancer.
PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVE: I. To describe the toxicities of each of the arms of the trial when used for patients with advanced/metastatic endometrial cancer. TERTIARY OBJECTIVES: 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
73
Providence Saint Joseph Medical Center/Disney Family Cancer Center
Burbank, California, United States
Stanford Cancer Institute
Palo Alto, California, United States
University of California San Diego
San Diego, California, United States
Colorado Gynecologic Oncology Group
Aurora, Colorado, United States
University of Colorado Cancer Center - Anschutz Cancer Pavilion
Aurora, Colorado, United States
Percentage of Participants With a Confirmed Objective Tumor Response Using RECIST Version 1.0
RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.
Time frame: Radiologic tumor evaluations at baseline and every 6 weeks for the first 24 weeks; then repeated every 12 weeks until disease progression. Repeat after treatment discontinuation if patient was taken off study for reasons other than progression.
Duration of Overall Survival (OS)
Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
Time frame: Every 6 weeks during treatment, then every 3 months for one year.
Duration of Progression-free Survival (PFS)
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions assessed radiographically and 50% increase if the only target lesion is a solitary pelvic mass measured by physical exam, or unequivocal progression of a non-target lesion, or the appearance of new lesions.
Time frame: Radiologic tumor evaluations at baseline and every six weeks for the first 24 weeks and then repeated every 12 weeks until disease progression. Repeat after treatment discontinuation if patient was taken off study for reasons other than progression.
Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0
Number of participants with a maximum grade of 3 or higher during the treatment period.
Time frame: Assessed every 6 weeks while on treatment, 30 days after the last cycle of treatment.
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