Temsirolimus With or Without Megestrol Acetate and Tamoxifen Citrate in Treating Patients With Advanced, Persistent, or Recurrent Endometrial Cancer
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|ClinicalTrials.gov Identifier: NCT00729586|
Recruitment Status : Completed
First Posted : August 7, 2008
Results First Posted : August 27, 2018
Last Update Posted : July 23, 2019
|Condition or disease||Intervention/treatment||Phase|
|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|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||73 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||September 2008|
|Actual Primary Completion Date :||February 2017|
|Actual Study Completion Date :||February 2017|
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
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
Drug: Megestrol Acetate
Drug: Tamoxifen Citrate
- Percentage of Participants With a Confirmed Objective Tumor Response Using RECIST Version 1.0 [ 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. ]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.
- Duration of Overall Survival (OS) [ Time Frame: Every 6 weeks during treatment, then every 3 months for one year. ]Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
- Duration of Progression-free Survival (PFS) [ 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. ]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.
- Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 [ Time Frame: Assessed every 6 weeks while on treatment, 30 days after the last cycle of treatment. ]Number of participants with a maximum grade of 3 or higher during the treatment period.
- Number of Participants and Their Levels of Expression of the Candidate Markers [ Time Frame: Baseline ]The levels of expression of the candidate markers measured prior to study treatment are tabulated. The expressions being tabulated include immunohistochemical expression of hormone receptors. The hormone receptors are estrogen receptor positive, progesterone receptors-A, progesterone receptor-B, PAKT Positive and PTEN Positive. The associations between the immunohistochemical expression of these biomarkers and between these biomarkers and treatment, outcome or clinical characteristics are reported for future investigation.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00729586
|Principal Investigator:||Gini Fleming||NRG Oncology|