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Temsirolimus With or Without ...

Temsirolimus With or Without Megestrol Acetate and Tamoxifen Citrate in Treating Patients With Advanced, Persistent, or Recurrent Endometrial Cancer

Last Updated: 2019-07-23

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

73 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-09-30

Study Completion Date

2017-02-28

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Temsirolimus

Intervention Type DRUG

Given IV

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.

Group Type EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Megestrol Acetate

Intervention Type DRUG

Given PO

Tamoxifen Citrate

Intervention Type DRUG

Given PO

Temsirolimus

Intervention Type DRUG

Given IV

Interventions

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Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Megestrol Acetate

Given PO

Intervention Type DRUG

Tamoxifen Citrate

Given PO

Intervention Type DRUG

Temsirolimus

Given IV

Intervention Type DRUG

Other Intervention Names

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17-Hydroxy-6-methylpregna-4,6-diene-3,20-dione acetate 17.alpha.-Acetoxy-6-methylpregna-4,6-diene-3,20-dione 6-Dehydro-6-methyl-17.alpha.-acetoxyprogesterone 6-Methyl-6-dehydro-17.alpha.-acetoxyprogesterone BDH 1298 BDH-1298 Maygace Megace Megestat Megestil Niagestin Ovaban Pallace SC-10363 Apo-Tamox Clonoxifen Dignotamoxi Ebefen Emblon Estroxyn Fentamox Gen-Tamoxifen Genox ICI 46,474 ICI-46474 Jenoxifen Kessar Ledertam Lesporene Nolgen Noltam Nolvadex Nolvadex-D Nourytam Novo-Tamoxifen Novofen Noxitem Oestrifen Oncotam PMS-Tamoxifen Soltamox TAM Tamax Tamaxin Tamifen Tamizam Tamofen Tamoxasta Tamoxifeni Citras Zemide CCI-779 CCI-779 Rapamycin Analog Cell Cycle Inhibitor 779 Rapamycin Analog Rapamycin Analog CCI-779 Torisel

Eligibility Criteria

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Inclusion Criteria

* 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)
* Triglycerides =\< 400 mg/dL (fasting)
* Albumin \>= 3.0 mg/dL
* At least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: hysterectomy, resection of a lung nodule-minor: a Port-A-Cath placement)
* Patients who have met the pre-entry requirements
* Patients must have signed an approved informed consent including Health Insurance Portability and Accountability Act (HIPAA) authorization

Exclusion Criteria

* 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

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gini Fleming

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

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Providence Saint Joseph Medical Center/Disney Family Cancer Center

Burbank, California, United States

Site Status

Stanford Cancer Institute

Palo Alto, California, United States

Site Status

University of California San Diego

San Diego, California, United States

Site Status

Colorado Gynecologic Oncology Group

Aurora, Colorado, United States

Site Status

University of Colorado Cancer Center - Anschutz Cancer Pavilion

Aurora, Colorado, United States

Site Status

Hartford Hospital

Hartford, Connecticut, United States

Site Status

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, United States

Site Status

The Hospital of Central Connecticut

New Britain, Connecticut, United States

Site Status

Beebe Medical Center

Lewes, Delaware, United States

Site Status

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

Site Status

John B Amos Cancer Center

Columbus, Georgia, United States

Site Status

Memorial University Medical Center

Savannah, Georgia, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Sudarshan K Sharma MD Limted-Gynecologic Oncology

Hinsdale, Illinois, United States

Site Status

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

Saint Vincent Hospital and Health Care Center

Indianapolis, Indiana, United States

Site Status

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Site Status

Menorah Medical Center

Overland Park, Kansas, United States

Site Status

Radiation Oncology Practice Corporation Southwest

Overland Park, Kansas, United States

Site Status

Saint Luke's South Hospital

Overland Park, Kansas, United States

Site Status

Shawnee Mission Medical Center-KCCC

Shawnee Mission, Kansas, United States

Site Status

Sinai Hospital of Baltimore

Baltimore, Maryland, United States

Site Status

MedStar Franklin Square Medical Center/Weinberg Cancer Institute

Baltimore, Maryland, United States

Site Status

Union Hospital of Cecil County

Elkton, Maryland, United States

Site Status

University of Massachusetts Memorial Health Care

Worcester, Massachusetts, United States

Site Status

University of Massachusetts Medical School

Worcester, Massachusetts, United States

Site Status

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, United States

Site Status

Michigan Cancer Research Consortium NCORP

Ann Arbor, Michigan, United States

Site Status

Bronson Battle Creek

Battle Creek, Michigan, United States

Site Status

Spectrum Health Big Rapids Hospital

Big Rapids, Michigan, United States

Site Status

Beaumont Hospital-Dearborn

Dearborn, Michigan, United States

Site Status

Saint John Hospital and Medical Center

Detroit, Michigan, United States

Site Status

Green Bay Oncology - Escanaba

Escanaba, Michigan, United States

Site Status

Hurley Medical Center

Flint, Michigan, United States

Site Status

Genesys Regional Medical Center-West Flint Campus

Flint, Michigan, United States

Site Status

Cancer Research Consortium of West Michigan NCORP

Grand Rapids, Michigan, United States

Site Status

Mercy Health Saint Mary's

Grand Rapids, Michigan, United States

Site Status

Spectrum Health at Butterworth Campus

Grand Rapids, Michigan, United States

Site Status

Green Bay Oncology - Iron Mountain

Iron Mountain, Michigan, United States

Site Status

Allegiance Health

Jackson, Michigan, United States

Site Status

Sparrow Hospital

Lansing, Michigan, United States

Site Status

Saint Mary Mercy Hospital

Livonia, Michigan, United States

Site Status

Mercy Health Mercy Campus

Muskegon, Michigan, United States

Site Status

Saint Joseph Mercy Oakland

Pontiac, Michigan, United States

Site Status

Lake Huron Medical Center

Port Huron, Michigan, United States

Site Status

William Beaumont Hospital-Royal Oak

Royal Oak, Michigan, United States

Site Status

Saint Mary's of Michigan

Saginaw, Michigan, United States

Site Status

Munson Medical Center

Traverse City, Michigan, United States

Site Status

Saint John Macomb-Oakland Hospital

Warren, Michigan, United States

Site Status

Metro Health Hospital

Wyoming, Michigan, United States

Site Status

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status