Temsirolimus With or Without Megestrol Acetate and Tamoxifen Citrate in Treating Patients With Advanced, Persistent, or Recurrent Endometrial Cancer
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
5 other identifiers
interventional
73
1 country
108
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Sep 2008
Longer than P75 for phase_2
108 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 6, 2008
CompletedFirst Posted
Study publicly available on registry
August 7, 2008
CompletedStudy Start
First participant enrolled
September 1, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2017
CompletedResults Posted
Study results publicly available
August 27, 2018
CompletedJuly 23, 2019
July 1, 2019
8.4 years
August 6, 2008
June 12, 2018
July 19, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
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.
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.
Secondary Outcomes (3)
Duration of Overall Survival (OS)
Every 6 weeks during treatment, then every 3 months for one year.
Duration of Progression-free Survival (PFS)
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
Assessed every 6 weeks while on treatment, 30 days after the last cycle of treatment.
Other Outcomes (1)
Number of Participants and Their Levels of Expression of the Candidate Markers
Baseline
Study Arms (2)
Arm I (temsirolimus)
EXPERIMENTALPatients 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 (temsirolimus, megestrol acetate, tamoxifen citrate)
EXPERIMENTALPatients 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.
Interventions
Correlative studies
Given PO
Given PO
Given IV
Eligibility Criteria
You may qualify if:
- Patients must have histologically confirmed advanced (International Federation of Gynecologists and Obstetricians \[FIGO\] stage III or IV), persistent, or recurrent endometrial carcinoma, which is not likely to be curable by surgery or radiotherapy; histologic documentation of the recurrence is not required
- All patients must have measurable disease; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each lesion must be \>= 20 mm when measured by conventional techniques, including palpation, plain x-ray, computed tomography (CT), and magnetic resonance imaging (MRI), or \>= 10 mm when measured by spiral CT
- Patients must have at least one "target lesion" to be used to assess response, as defined by Response Evaluation Criteria In Solid Tumors (RECIST); tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented
- Prior chemoradiotherapy for a pelvic recurrence is permitted; prior chemotherapy in the adjuvant setting for stage I, II, or III disease is permitted
- Note: no prior chemotherapy in the setting of stage IV disease is permitted unless the patient was without evidence of disease at the completion of chemotherapy and had at least six months of progression-free survival since the completion of chemotherapy
- Regardless of circumstances, no more than one prior chemotherapy regimen (including chemoradiotherapy) is permitted
- Patient must be able to take p.o. medications
- Performance status must be 0-2
- Absolute neutrophil count \>= 1,500/mcL
- Platelets \>= 100,000/mcL
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 2.5 times institutional upper limit of normal v 3.0 (=\< 5 times upper limit of normal \[ULN\] for subjects with liver metastases)
- Alkaline phosphatase =\< 2.5 times institutional upper limit of normal v 3.0 (=\< 5 times ULN for subjects with liver metastases)
- Creatinine =\< 1.5 times normal institutional upper limit of normal
- Cholesterol =\< 350 mg/dL (fasting)
- +5 more criteria
You may not qualify if:
- Patients with Gynecologic Oncology Group (GOG) performance status of 3 or 4
- Patients cannot be receiving enzyme-inducing antiepileptic drugs (EIAEDs; e.g., phenytoin, carbamazepine, phenobarbital) nor any other cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducer such as rifampin or St. John's wort, as these may decrease temsirolimus levels; use of agents that potently inhibit CYP3A (and hence may raise temsirolimus levels), such as ketoconazole, is discouraged, but not specifically prohibited; the appropriateness of use of such agents is left to physician discretion
- All concomitant medications must be recorded at baseline
- Patients on maintenance corticosteroids are ineligible with the exception of short term use (fewer than 5 days)
- Patients known to have congestive heart failure; patients with baseline requirement for oxygen; patients with serious concomitant illness that, in the opinion of the treating physician, will place patient at unreasonable risk from therapy on this protocol
- Patients with a history of unprovoked deep vein thrombosis (DVT) or pulmonary embolism (PE), unless patient is maintained on anticoagulation for the duration of the trial; while the exact definition of "provoked" is left to the treating physician, a DVT in the setting of pelvic surgery or trauma would be considered "provoked"
- Women of child-bearing potential must have a negative pregnancy test prior to treatment on study; breastfeeding should be discontinued if the mother is treated with temsirolimus
- Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control or abstinence; oral contraceptives \[also known as "the pill"\] are not acceptable) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Patients with a concomitant invasive malignancy or a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the past five years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
- Patients who have received hormonal therapy or biologic therapy as treatment for endometrial carcinoma
- Patients who have received chemotherapy directed at metastatic or recurrent endometrial carcinoma
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- National Cancer Institute (NCI)lead
- NRG Oncologycollaborator
Study Sites (108)
Providence Saint Joseph Medical Center/Disney Family Cancer Center
Burbank, California, 91505, United States
Stanford Cancer Institute
Palo Alto, California, 94304, United States
University of California San Diego
San Diego, California, 92103, United States
Colorado Gynecologic Oncology Group
Aurora, Colorado, 80010, United States
University of Colorado Cancer Center - Anschutz Cancer Pavilion
Aurora, Colorado, 80045, United States
Hartford Hospital
Hartford, Connecticut, 06102, United States
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, 06105, United States
The Hospital of Central Connecticut
New Britain, Connecticut, 06050, United States
Beebe Medical Center
Lewes, Delaware, 19958, United States
Christiana Care Health System-Christiana Hospital
Newark, Delaware, 19718, United States
John B Amos Cancer Center
Columbus, Georgia, 31904, United States
Memorial University Medical Center
Savannah, Georgia, 31404, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Sudarshan K Sharma MD Limted-Gynecologic Oncology
Hinsdale, Illinois, 60521, United States
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202, United States
Saint Vincent Hospital and Health Care Center
Indianapolis, Indiana, 46260, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
Menorah Medical Center
Overland Park, Kansas, 66209, United States
Radiation Oncology Practice Corporation Southwest
Overland Park, Kansas, 66210, United States
Saint Luke's South Hospital
Overland Park, Kansas, 66213, United States
Shawnee Mission Medical Center-KCCC
Shawnee Mission, Kansas, 66204, United States
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215, United States
MedStar Franklin Square Medical Center/Weinberg Cancer Institute
Baltimore, Maryland, 21237, United States
Union Hospital of Cecil County
Elkton, Maryland, 21921, United States
University of Massachusetts Memorial Health Care
Worcester, Massachusetts, 01605, United States
University of Massachusetts Medical School
Worcester, Massachusetts, 01655, United States
Saint Joseph Mercy Hospital
Ann Arbor, Michigan, 48106-0995, United States
Michigan Cancer Research Consortium NCORP
Ann Arbor, Michigan, 48106, United States
Bronson Battle Creek
Battle Creek, Michigan, 49017, United States
Spectrum Health Big Rapids Hospital
Big Rapids, Michigan, 49307, United States
Beaumont Hospital-Dearborn
Dearborn, Michigan, 48124, United States
Saint John Hospital and Medical Center
Detroit, Michigan, 48236, United States
Green Bay Oncology - Escanaba
Escanaba, Michigan, 49829, United States
Hurley Medical Center
Flint, Michigan, 48502, United States
Genesys Regional Medical Center-West Flint Campus
Flint, Michigan, 48532, United States
Cancer Research Consortium of West Michigan NCORP
Grand Rapids, Michigan, 49503, United States
Mercy Health Saint Mary's
Grand Rapids, Michigan, 49503, United States
Spectrum Health at Butterworth Campus
Grand Rapids, Michigan, 49503, United States
Green Bay Oncology - Iron Mountain
Iron Mountain, Michigan, 49801, United States
Allegiance Health
Jackson, Michigan, 49201, United States
Sparrow Hospital
Lansing, Michigan, 48912, United States
Saint Mary Mercy Hospital
Livonia, Michigan, 48154, United States
Mercy Health Mercy Campus
Muskegon, Michigan, 49444, United States
Saint Joseph Mercy Oakland
Pontiac, Michigan, 48341, United States
Lake Huron Medical Center
Port Huron, Michigan, 48060, United States
William Beaumont Hospital-Royal Oak
Royal Oak, Michigan, 48073, United States
Saint Mary's of Michigan
Saginaw, Michigan, 48601, United States
Munson Medical Center
Traverse City, Michigan, 49684, United States
Saint John Macomb-Oakland Hospital
Warren, Michigan, 48093, United States
Metro Health Hospital
Wyoming, Michigan, 49519, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Centerpoint Medical Center LLC
Independence, Missouri, 64057, United States
Truman Medical Center
Kansas City, Missouri, 64108, United States
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, 64111, United States
Radiation Oncology Practice Corporation South
Kansas City, Missouri, 64114, United States
Saint Joseph Health Center
Kansas City, Missouri, 64114, United States
North Kansas City Hospital
Kansas City, Missouri, 64116, United States
Heartland Hematology and Oncology Associates Incorporated
Kansas City, Missouri, 64118, United States
Research Medical Center
Kansas City, Missouri, 64132, United States
Radiation Oncology Practice Corporation - North
Kansas City, Missouri, 64154, United States
Saint Luke's East - Lee's Summit
Lee's Summit, Missouri, 64086, United States
Liberty Radiation Oncology Center
Liberty, Missouri, 64068, United States
Heartland Regional Medical Center
Saint Joseph, Missouri, 64506, United States
Saint Joseph Oncology Inc
Saint Joseph, Missouri, 64507, United States
Mercy Hospital Springfield
Springfield, Missouri, 65804, United States
Women's Cancer Center of Nevada
Las Vegas, Nevada, 89169, United States
Cooper Hospital University Medical Center
Camden, New Jersey, 08103, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87102, United States
Southwest Gynecologic Oncology Associates Inc
Albuquerque, New Mexico, 87106, United States
Women's Cancer Care Associates LLC
Albany, New York, 12208, United States
North Shore University Hospital
Manhasset, New York, 11030, United States
Long Island Jewish Medical Center
New Hyde Park, New York, 11040, United States
North Shore-LIJ Health System/Center for Advanced Medicine
New Hyde Park, New York, 11040, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065, United States
Stony Brook University Medical Center
Stony Brook, New York, 11794, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203, United States
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, 28204, United States
University of Cincinnati/Barrett Cancer Center
Cincinnati, Ohio, 45219, United States
MetroHealth Medical Center
Cleveland, Ohio, 44109, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Oklahoma Cancer Specialists and Research Institute-Tulsa
Tulsa, Oklahoma, 74146, United States
Legacy Good Samaritan Hospital and Medical Center
Portland, Oregon, 97210, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
Compass Oncology Rose Quarter
Portland, Oregon, 97227, United States
Abington Memorial Hospital
Abington, Pennsylvania, 19001, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
Reading Hospital
West Reading, Pennsylvania, 19611, United States
Women and Infants Hospital
Providence, Rhode Island, 02905, United States
Black Hills Obstetrics and Gynecology
Rapid City, South Dakota, 57701, United States
Parkland Memorial Hospital
Dallas, Texas, 75235, United States
Clements University Hospital
Dallas, Texas, 75390, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
Carilion Clinic Gynecological Oncology
Roanoke, Virginia, 24016, United States
Green Bay Oncology at Saint Vincent Hospital
Green Bay, Wisconsin, 54301-3526, United States
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301, United States
Green Bay Oncology Limited at Saint Mary's Hospital
Green Bay, Wisconsin, 54303, United States
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin, 54303, United States
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792, United States
Holy Family Memorial Hospital
Manitowoc, Wisconsin, 54221, United States
Bay Area Medical Center
Marinette, Wisconsin, 54143, United States
Green Bay Oncology - Oconto Falls
Oconto Falls, Wisconsin, 54154, United States
Green Bay Oncology - Sturgeon Bay
Sturgeon Bay, Wisconsin, 54235, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The combination arm was closed after the first stage of accrual due to an excess of venous thromboses.
Results Point of Contact
- Title
- Angela Kuras on behalf of Virginia Filiaci
- Organization
- NRG Oncology
Study Officials
- PRINCIPAL INVESTIGATOR
Gini Fleming
NRG Oncology
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 6, 2008
First Posted
August 7, 2008
Study Start
September 1, 2008
Primary Completion
February 1, 2017
Study Completion
February 1, 2017
Last Updated
July 23, 2019
Results First Posted
August 27, 2018
Record last verified: 2019-07