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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00729586
• Collaborator: NRG Oncology (Other)
• Enrollment: 73
• Locations: 108
• Arms: 2
• Duration (Months): 101
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

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

Detailed Description

PRIMARY OBJECTIVES:

1. 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.

2. Time to progression and number of patients remaining on study therapy at 24 weeks.

SECONDARY OBJECTIVE:

1. To describe the toxicities of each of the arms of the trial when used for patients with advanced/metastatic endometrial cancer.

TERTIARY OBJECTIVES:

1. 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.

2. 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 Design

• Study Type: Interventional
• Actual Enrollment: 73 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• 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
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Feb 1, 2017
• Actual Study Completion Date: Feb 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
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 studies; Drug: Temsirolimus; Given IV; Other Names: CCI-779 CCI-779 Rapamycin Analog Cell Cycle Inhibitor 779 Rapamycin Analog Rapamycin Analog CCI-779 Torisel
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 studies; Drug: Megestrol Acetate; Given PO; Other Names: 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 ; Drug: Tamoxifen Citrate; Given PO; Other Names: 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 ; Drug: Temsirolimus; Given IV; Other Names: CCI-779 CCI-779 Rapamycin Analog Cell Cycle Inhibitor 779 Rapamycin Analog Rapamycin Analog CCI-779 Torisel

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a Confirmed Objective Tumor Response Using RECIST Version 1.0 [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.

Secondary Outcome Measures

1. Duration of Overall Survival (OS) [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.

2. 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.]

   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.

3. 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.]

   Number of participants with a maximum grade of 3 or higher during the treatment period.

Other Outcome Measures

1. Number of Participants and Their Levels of Expression of the Candidate Markers [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
2	Stanford Cancer Institute	Palo Alto	California	United States	94304
3	University of California San Diego	San Diego	California	United States	92103
4	Colorado Gynecologic Oncology Group	Aurora	Colorado	United States	80010
5	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado	United States	80045
6	Hartford Hospital	Hartford	Connecticut	United States	06102
7	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut	United States	06105
8	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
9	Beebe Medical Center	Lewes	Delaware	United States	19958
10	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
11	John B Amos Cancer Center	Columbus	Georgia	United States	31904
12	Memorial University Medical Center	Savannah	Georgia	United States	31404
13	Rush University Medical Center	Chicago	Illinois	United States	60612
14	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
15	Sudarshan K Sharma MD Limted-Gynecologic Oncology	Hinsdale	Illinois	United States	60521
16	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
17	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana	United States	46260
18	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
19	Menorah Medical Center	Overland Park	Kansas	United States	66209
20	Radiation Oncology Practice Corporation Southwest	Overland Park	Kansas	United States	66210
21	Saint Luke's South Hospital	Overland Park	Kansas	United States	66213
22	Shawnee Mission Medical Center-KCCC	Shawnee Mission	Kansas	United States	66204
23	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
24	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland	United States	21237
25	Union Hospital of Cecil County	Elkton	Maryland	United States	21921
26	University of Massachusetts Memorial Health Care	Worcester	Massachusetts	United States	01605
27	University of Massachusetts Medical School	Worcester	Massachusetts	United States	01655
28	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
29	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan	United States	48106
30	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
31	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan	United States	49307
32	Beaumont Hospital-Dearborn	Dearborn	Michigan	United States	48124
33	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
34	Green Bay Oncology - Escanaba	Escanaba	Michigan	United States	49829
35	Hurley Medical Center	Flint	Michigan	United States	48502
36	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan	United States	48532
37	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan	United States	49503
38	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
39	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
40	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan	United States	49801
41	Allegiance Health	Jackson	Michigan	United States	49201
42	Sparrow Hospital	Lansing	Michigan	United States	48912
43	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
44	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
45	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
46	Lake Huron Medical Center	Port Huron	Michigan	United States	48060
47	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
48	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
49	Munson Medical Center	Traverse City	Michigan	United States	49684
50	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
51	Metro Health Hospital	Wyoming	Michigan	United States	49519
52	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota	United States	55455
53	Centerpoint Medical Center LLC	Independence	Missouri	United States	64057
54	Truman Medical Center	Kansas City	Missouri	United States	64108
55	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
56	Radiation Oncology Practice Corporation South	Kansas City	Missouri	United States	64114
57	Saint Joseph Health Center	Kansas City	Missouri	United States	64114
58	North Kansas City Hospital	Kansas City	Missouri	United States	64116
59	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri	United States	64118
60	Research Medical Center	Kansas City	Missouri	United States	64132
61	Radiation Oncology Practice Corporation - North	Kansas City	Missouri	United States	64154
62	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
63	Liberty Radiation Oncology Center	Liberty	Missouri	United States	64068
64	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
65	Saint Joseph Oncology Inc	Saint Joseph	Missouri	United States	64507
66	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
67	Women's Cancer Center of Nevada	Las Vegas	Nevada	United States	89169
68	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
69	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
70	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
71	Southwest Gynecologic Oncology Associates Inc	Albuquerque	New Mexico	United States	87106
72	Women's Cancer Care Associates LLC	Albany	New York	United States	12208
73	North Shore University Hospital	Manhasset	New York	United States	11030
74	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
75	North Shore-LIJ Health System/Center for Advanced Medicine	New Hyde Park	New York	United States	11040
76	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
77	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
78	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
79	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
80	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
81	University of Cincinnati/Barrett Cancer Center	Cincinnati	Ohio	United States	45219
82	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
83	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
84	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma	United States	74146
85	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon	United States	97210
86	Providence Portland Medical Center	Portland	Oregon	United States	97213
87	Compass Oncology Rose Quarter	Portland	Oregon	United States	97227
88	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
89	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
90	Reading Hospital	West Reading	Pennsylvania	United States	19611
91	Women and Infants Hospital	Providence	Rhode Island	United States	02905
92	Black Hills Obstetrics and Gynecology	Rapid City	South Dakota	United States	57701
93	Parkland Memorial Hospital	Dallas	Texas	United States	75235
94	Clements University Hospital	Dallas	Texas	United States	75390
95	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
96	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
97	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908
98	Carilion Clinic Gynecological Oncology	Roanoke	Virginia	United States	24016
99	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
100	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
101	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
102	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin	United States	54303
103	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
104	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
105	Holy Family Memorial Hospital	Manitowoc	Wisconsin	United States	54221
106	Bay Area Medical Center	Marinette	Wisconsin	United States	54143
107	Green Bay Oncology - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
108	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235

Sponsors and Collaborators

• National Cancer Institute (NCI)
• NRG Oncology

Investigators

• Principal Investigator: Gini Fleming, NRG Oncology

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 22, 2014

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00729586
• Other Study ID Numbers: NCI-2009-01085; NCI-2009-01085; GOG-0248; CDR0000609740; GOG-0248; GOG-0248; U10CA180868; U10CA027469
• First Posted: Aug 7, 2008
• Last Update Posted: Jul 23, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Carcinoma; Endometrial Neoplasms; Recurrence; Tamoxifen; Sirolimus; Megestrol; Megestrol Acetate

Study Results

Participant Flow

Recruitment Details	Seventy-three patients were registered to this trial between 9/29/08 and 11/22/10. On 10/19/09 the trial was suspended and the combination arm was permanently closed to accrual because an excess of venous thromboses was noted. The single agent arm continued to the second stage of accrual on 5/24/2010.

Arm/Group Title	Arm 1: Temsirolimus	Arm 2: Megestrol Acetate+Tamoxifen+ Temsirolimus
Arm/Group Description	Temsirolimus IV 25 mg (flat dose) weekly	Megestrol Acetate (MA) 80 mg bid for three weeks alternating with Tamoxifen (T) 20 mg bid for 3 weeks PLUS Temsirolimus IV 25 mg (flat dose) weekly
Period Title: Overall Study
STARTED	51	22
COMPLETED	50	21
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Arm 1: Temsirolimus	Arm 2: Megestrol Acetate+Tamoxifen+ Temsirolimus	Total
Arm/Group Description	Temsirolimus IV 25 mg (flat dose) weekly	Megestrol Acetate (MA) 80 mg bid for three weeks alternating with Tamoxifen (T) 20 mg bid for 3 weeks PLUS Temsirolimus IV 25 mg (flat dose) weekly	Total of all reporting groups
Overall Participants	50	21	71
Age, Customized (Count of Participants)
40-49 years	4 8%	0 0%	4 5.6%
50-59 years	9 18%	6 28.6%	15 21.1%
60-69 years	26 52%	10 47.6%	36 50.7%
70-79 years	8 16%	3 14.3%	11 15.5%
>=80 years	3 6%	2 9.5%	5 7%
Sex: Female, Male (Count of Participants)
Female	50 100%	21 100%	71 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	5 10%	1 4.8%	6 8.5%
White	45 90%	20 95.2%	65 91.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Confirmed Objective Tumor Response Using RECIST Version 1.0
Description	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.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Arm 1: Temsirolimus	Arm 2: Megestrol Acetate+Tamoxifen+ Temsirolimus
Arm/Group Description	Temsirolimus IV 25 mg (flat dose) weekly	Megestrol Acetate (MA) 80 mg bid for three weeks alternating with Tamoxifen (T) 20 mg bid for 3 weeks PLUS Temsirolimus IV 25 mg (flat dose) weekly
Measure Participants	50	21
Number (94% Confidence Interval) [percentage of participants]	22 44%	14.3 68.1%

2. Secondary Outcome

Title	Duration of Overall Survival (OS)
Description	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.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Arm 1: Temsirolimus	Arm 2: Megestrol Acetate+Tamoxifen+ Temsirolimus
Arm/Group Description	Temsirolimus IV 25 mg (flat dose) weekly	Megestrol Acetate (MA) 80 mg bid for three weeks alternating with Tamoxifen (T) 20 mg bid for 3 weeks PLUS Temsirolimus IV 25 mg (flat dose) weekly
Measure Participants	50	21
Median (95% Confidence Interval) [months]	13.3	9.6

3. Secondary Outcome

Title	Duration of Progression-free Survival (PFS)
Description	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.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Arm 1: Temsirolimus	Arm 2: Megestrol Acetate+Tamoxifen+ Temsirolimus
Arm/Group Description	Temsirolimus IV 25 mg (flat dose) weekly	Megestrol Acetate (MA) 80 mg bid for three weeks alternating with Tamoxifen (T) 20 mg bid for 3 weeks PLUS Temsirolimus IV 25 mg (flat dose) weekly
Measure Participants	50	21
Median (95% Confidence Interval) [months]	5.6	4.2

4. Secondary Outcome

Title	Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0
Description	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.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Arm 1: Temsirolimus	Arm 2: Megestrol Acetate+Tamoxifen+ Temsirolimus
Arm/Group Description	Temsirolimus IV 25 mg (flat dose) weekly	Megestrol Acetate (MA) 80 mg bid for three weeks alternating with Tamoxifen (T) 20 mg bid for 3 weeks PLUS Temsirolimus IV 25 mg (flat dose) weekly
Measure Participants	50	21
Count of Participants [Participants]	29 58%	15 71.4%

5. Other Pre-specified Outcome

Title	Number of Participants and Their Levels of Expression of the Candidate Markers
Description	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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Eligible and treated patients with primary tumor specimen

Arm/Group Title	Receptor Analysis
Arm/Group Description	Eligible and treated patients with primary tumor specimen
Measure Participants	56
Estrogen Receptor Positive	20 40%
Progesterone Receptor Positive	30 60%
Progesterone Receptor B Positive	35 70%
PAKT Positive	11 22%
PTEN Positive	30 60%

Adverse Events

Time Frame	Assessed every 6 weeks while on treatment, 30 days after the last cycle of treatment, and up to 1 year in follow-up
Arm/Group Title	Arm 1: Temsirolimus		Arm 2: Megestrol Acetate+Tamoxifen+ Temsirolimus
Arm/Group Description	Temsirolimus IV 25 mg (flat dose) weekly		Megestrol Acetate (MA) 80 mg bid for three weeks alternating with Tamoxifen (T) 20 mg bid for 3 weeks PLUS Temsirolimus IV 25 mg (flat dose) weekly
All Cause Mortality
	Arm 1: Temsirolimus		Arm 2: Megestrol Acetate+Tamoxifen+ Temsirolimus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/50 (66%)		16/21 (76.2%)
Serious Adverse Events
	Arm 1: Temsirolimus		Arm 2: Megestrol Acetate+Tamoxifen+ Temsirolimus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/50 (36%)		13/21 (61.9%)
Blood and lymphatic system disorders
Edema: Limb	0/50 (0%)		1/21 (4.8%)
Cardiac disorders
Cardiac Arrhythmia - Other	1/50 (2%)		0/21 (0%)
Cardiac Ischemia/Infarction	0/50 (0%)		1/21 (4.8%)
Gastrointestinal disorders
Obstruction, Gi - Small Bowel Nos	2/50 (4%)		0/21 (0%)
Colitis	1/50 (2%)		0/21 (0%)
Vomiting	2/50 (4%)		1/21 (4.8%)
Anorexia	1/50 (2%)		0/21 (0%)
Nausea	1/50 (2%)		0/21 (0%)
General disorders
Fatigue	2/50 (4%)		0/21 (0%)
Death No Ctcae Term - Disease Progression Nos	1/50 (2%)		2/21 (9.5%)
Death No Ctcae Term - Sudden Death	0/50 (0%)		1/21 (4.8%)
Pain: Extremity-Limb	0/50 (0%)		1/21 (4.8%)
Pain: Back	1/50 (2%)		0/21 (0%)
Infections and infestations
Inf W/Nml Or Gr 1 Or 2 Anc: Joint	1/50 (2%)		0/21 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Skin(Cellulitis)	1/50 (2%)		0/21 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Urinary Tract Nos	1/50 (2%)		0/21 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Abdomen Nos	1/50 (2%)		0/21 (0%)
Metabolism and nutrition disorders
Creatinine	1/50 (2%)		0/21 (0%)
Hypocalcemia	1/50 (2%)		0/21 (0%)
Hypokalemia	1/50 (2%)		2/21 (9.5%)
Hypomagnesemia	1/50 (2%)		0/21 (0%)
Musculoskeletal and connective tissue disorders
Muscle Weakness - Whole Body/Generalized	1/50 (2%)		0/21 (0%)
Renal and urinary disorders
Obstruction, Gu - Ureter	1/50 (2%)		0/21 (0%)
Respiratory, thoracic and mediastinal disorders
Dlco	1/50 (2%)		0/21 (0%)
Pneumonitis	1/50 (2%)		0/21 (0%)
Skin and subcutaneous tissue disorders
Ulceration	1/50 (2%)		0/21 (0%)
Surgical and medical procedures
Intra-Op Injury: Other	1/50 (2%)		0/21 (0%)
Vascular disorders
Thrombosis/Embolism (Vascular Access-Related)	0/50 (0%)		1/21 (4.8%)
Thrombosis/Thrombus/Embolism	2/50 (4%)		5/21 (23.8%)
Other (Not Including Serious) Adverse Events
	Arm 1: Temsirolimus		Arm 2: Megestrol Acetate+Tamoxifen+ Temsirolimus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/50 (100%)		21/21 (100%)
Blood and lymphatic system disorders
Neutrophils	15/50 (30%)		4/21 (19%)
Platelets	15/50 (30%)		11/21 (52.4%)
Blood/Bone Marrow - Other	2/50 (4%)		0/21 (0%)
Leukocytes	27/50 (54%)		7/21 (33.3%)
Lymphopenia	2/50 (4%)		1/21 (4.8%)
Hemoglobin	39/50 (78%)		20/21 (95.2%)
Lymphedema-Related Fibrosis	0/50 (0%)		1/21 (4.8%)
Edema: Trunk/Genital	0/50 (0%)		1/21 (4.8%)
Edema: Limb	16/50 (32%)		10/21 (47.6%)
Edema: Head And Neck	2/50 (4%)		3/21 (14.3%)
Cardiac disorders
S/N Arrhythmia: Atrial Fibrillation	0/50 (0%)		1/21 (4.8%)
Palpitations	0/50 (0%)		1/21 (4.8%)
Cardiac Arrhythmia - Other	1/50 (2%)		0/21 (0%)
S/N Arrhythmia: Sinus Tachycardia	0/50 (0%)		1/21 (4.8%)
Cardiac Ischemia/Infarction	0/50 (0%)		1/21 (4.8%)
Hypertension	2/50 (4%)		0/21 (0%)
Lt Ventricular Systolic Dysfunction	0/50 (0%)		1/21 (4.8%)
Hypotension	0/50 (0%)		1/21 (4.8%)
Ear and labyrinth disorders
Auditory/Ear - Other	0/50 (0%)		1/21 (4.8%)
Tinnitus	1/50 (2%)		0/21 (0%)
Endocrine disorders
Hot Flashes	2/50 (4%)		4/21 (19%)
Eye disorders
Ocular/Visual - Other	1/50 (2%)		0/21 (0%)
Watery Eye	1/50 (2%)		0/21 (0%)
Dry Eye	1/50 (2%)		0/21 (0%)
Gastrointestinal disorders
Heartburn	1/50 (2%)		2/21 (9.5%)
Mucositis (Functional/Sympt) - Trachea	0/50 (0%)		1/21 (4.8%)
Ascites	2/50 (4%)		1/21 (4.8%)
Leak, Gi - Rectum	1/50 (2%)		0/21 (0%)
Dysphagia	1/50 (2%)		0/21 (0%)
Distention	3/50 (6%)		1/21 (4.8%)
Taste Alteration	10/50 (20%)		4/21 (19%)
Dry Mouth	2/50 (4%)		2/21 (9.5%)
Mucositis (Functional/Sympt) - Oral Cavity	7/50 (14%)		7/21 (33.3%)
Obstruction, Gi - Small Bowel Nos	3/50 (6%)		0/21 (0%)
Colitis	1/50 (2%)		0/21 (0%)
Mucositis (Clinical Exam) - Oral Cavity	10/50 (20%)		4/21 (19%)
Mucositis (Clinical Exam) - Anus	0/50 (0%)		1/21 (4.8%)
Vomiting	13/50 (26%)		4/21 (19%)
Anorexia	18/50 (36%)		4/21 (19%)
Dehydration	2/50 (4%)		1/21 (4.8%)
Constipation	15/50 (30%)		5/21 (23.8%)
Nausea	23/50 (46%)		3/21 (14.3%)
Diarrhea	16/50 (32%)		8/21 (38.1%)
General disorders
Constitutional Symptoms - Other	0/50 (0%)		1/21 (4.8%)
Sweating	1/50 (2%)		1/21 (4.8%)
Weight Gain	0/50 (0%)		2/21 (9.5%)
Fever	7/50 (14%)		3/21 (14.3%)
Weight Loss	8/50 (16%)		2/21 (9.5%)
Rigors/Chills	1/50 (2%)		2/21 (9.5%)
Fatigue	38/50 (76%)		18/21 (85.7%)
Insomnia	4/50 (8%)		7/21 (33.3%)
Death No Ctcae Term - Disease Progression Nos	1/50 (2%)		2/21 (9.5%)
Death No Ctcae Term - Sudden Death	0/50 (0%)		1/21 (4.8%)
Pain - Other	2/50 (4%)		4/21 (19%)
Pain: Urethra	0/50 (0%)		1/21 (4.8%)
Pain: Breast	0/50 (0%)		1/21 (4.8%)
Pain: Chest /Thorax Nos	1/50 (2%)		1/21 (4.8%)
Pain: Chest Wall	1/50 (2%)		1/21 (4.8%)
Pain: Throat/Pharynx/Larynx	2/50 (4%)		1/21 (4.8%)
Pain: Head/Headache	8/50 (16%)		4/21 (19%)
Pain: Neck	0/50 (0%)		1/21 (4.8%)
Pain: Extremity-Limb	6/50 (12%)		3/21 (14.3%)
Pain: Buttock	1/50 (2%)		0/21 (0%)
Pain: Back	9/50 (18%)		2/21 (9.5%)
Pain: Joint	4/50 (8%)		3/21 (14.3%)
Pain: Kidney	1/50 (2%)		0/21 (0%)
Pain: Bladder	1/50 (2%)		0/21 (0%)
Pain: Pain Nos	1/50 (2%)		2/21 (9.5%)
Pain: Stomach	1/50 (2%)		1/21 (4.8%)
Pain: Oral Cavity	2/50 (4%)		0/21 (0%)
Pain: Dental/Teeth/Peridontal	0/50 (0%)		1/21 (4.8%)
Pain: Abdominal Pain Nos	12/50 (24%)		6/21 (28.6%)
Pain: Muscle	4/50 (8%)		2/21 (9.5%)
Flu-Like Syndrome	0/50 (0%)		1/21 (4.8%)
Immune system disorders
Allergic Reaction/Hypersensitivity	1/50 (2%)		1/21 (4.8%)
Rhinitis	2/50 (4%)		3/21 (14.3%)
Infections and infestations
Inf W/Nml Or Gr 1 Or 2 Anc: Upper Airway Nos	0/50 (0%)		1/21 (4.8%)
Inf W/Nml Or Gr 1 Or 2 Anc: Paranasal	0/50 (0%)		1/21 (4.8%)
Inf W/Nml Or Gr 1 Or 2 Anc: Lung(Pneumonia)	0/50 (0%)		1/21 (4.8%)
Inf W/Nml Or Gr 1 Or 2 Anc: Eye Nos	1/50 (2%)		0/21 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Soft Tissue Nos	0/50 (0%)		1/21 (4.8%)
Inf W/Nml Or Gr 1 Or 2 Anc: Joint	1/50 (2%)		0/21 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Blood	1/50 (2%)		0/21 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Small Bowel Nos	1/50 (2%)		0/21 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Oral Cavity-Gums	0/50 (0%)		1/21 (4.8%)
Inf W/Nml Or Gr 1 Or 2 Anc: Skin(Cellulitis)	1/50 (2%)		1/21 (4.8%)
Inf Unknown Anc: Lung (Pneumonia)	1/50 (2%)		0/21 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Urinary Tract Nos	1/50 (2%)		0/21 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Abdomen Nos	1/50 (2%)		0/21 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Ungual (Nails)	1/50 (2%)		0/21 (0%)
Infection - Other	2/50 (4%)		0/21 (0%)
Colitis, Infectious (Eg.C. Difficile)	1/50 (2%)		0/21 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Nerve-Peripheral	1/50 (2%)		0/21 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Bronchus	0/50 (0%)		1/21 (4.8%)
Inf W/Nml Or Gr 1 Or 2 Anc: Mucosa	0/50 (0%)		1/21 (4.8%)
Inf Unknown Anc: Upper Airway Nos	1/50 (2%)		0/21 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Sinus	0/50 (0%)		1/21 (4.8%)
Inf Unknown Anc: Urinary Tract Nos	0/50 (0%)		1/21 (4.8%)
Inf Unknown Anc: Skin (Cellulitis)	0/50 (0%)		1/21 (4.8%)
Inf W/Nml Or Gr 1 Or 2 Anc: Kidney	1/50 (2%)		0/21 (0%)
Metabolism and nutrition disorders
Ast	5/50 (10%)		1/21 (4.8%)
Gfr	0/50 (0%)		1/21 (4.8%)
Metabolic/Laboratory - Other	1/50 (2%)		2/21 (9.5%)
Cholesterol,serum High	19/50 (38%)		7/21 (33.3%)
Creatinine	9/50 (18%)		4/21 (19%)
Hypoalbuminemia	7/50 (14%)		6/21 (28.6%)
Alt	4/50 (8%)		1/21 (4.8%)
Alkaline Phosphatase	7/50 (14%)		1/21 (4.8%)
Hypermagnesemia	0/50 (0%)		1/21 (4.8%)
Hypophosphatemia	1/50 (2%)		0/21 (0%)
Hyponatremia	6/50 (12%)		4/21 (19%)
Hypertriglyceridemia	20/50 (40%)		7/21 (33.3%)
Bicarbonate, Serum-Low	1/50 (2%)		0/21 (0%)
Hypernatremia	2/50 (4%)		0/21 (0%)
Hypocalcemia	8/50 (16%)		3/21 (14.3%)
Hyperkalemia	2/50 (4%)		0/21 (0%)
Hyperglycemia	9/50 (18%)		3/21 (14.3%)
Hypokalemia	10/50 (20%)		4/21 (19%)
Hypoglycemia	2/50 (4%)		2/21 (9.5%)
Hypercalcemia	1/50 (2%)		0/21 (0%)
Hypomagnesemia	3/50 (6%)		3/21 (14.3%)
Musculoskeletal and connective tissue disorders
Musculoskeletal/St: Other	1/50 (2%)		1/21 (4.8%)
Fracture	1/50 (2%)		1/21 (4.8%)
Extremity-Upper (Function)	2/50 (4%)		0/21 (0%)
Arthritis	1/50 (2%)		0/21 (0%)
Muscle Weakness - Whole Body/Generalized	3/50 (6%)		2/21 (9.5%)
Nervous system disorders
Syncope	1/50 (2%)		0/21 (0%)
Psychosis	0/50 (0%)		1/21 (4.8%)
Mood Alteration - Depression	2/50 (4%)		1/21 (4.8%)
Mood Alteration - Anxiety	4/50 (8%)		1/21 (4.8%)
Mood Alteration - Agitation	0/50 (0%)		1/21 (4.8%)
Tremor	0/50 (0%)		2/21 (9.5%)
Speech Impairment	1/50 (2%)		0/21 (0%)
Irritability	0/50 (0%)		1/21 (4.8%)
Confusion	2/50 (4%)		0/21 (0%)
Memory Impairment	1/50 (2%)		0/21 (0%)
Dizziness	3/50 (6%)		4/21 (19%)
Neuropathy-Sensory	7/50 (14%)		1/21 (4.8%)
Renal and urinary disorders
Renal/Genitourinary - Other	1/50 (2%)		0/21 (0%)
Stricture, Anastomotic, Gu - Ureter	0/50 (0%)		1/21 (4.8%)
Cystitis	1/50 (2%)		0/21 (0%)
Obstruction, Gu - Ureter	1/50 (2%)		0/21 (0%)
Incontinence, Urinary	1/50 (2%)		1/21 (4.8%)
Renal Failure	0/50 (0%)		1/21 (4.8%)
Urinary Frequency	1/50 (2%)		2/21 (9.5%)
Reproductive system and breast disorders
Breast	1/50 (2%)		0/21 (0%)
Vaginal Dryness	1/50 (2%)		0/21 (0%)
Sexual/Reproductive Function: Other	1/50 (2%)		0/21 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary: Other	5/50 (10%)		1/21 (4.8%)
Nasal/Paranasal Reactions	2/50 (4%)		2/21 (9.5%)
Bronchospasm	0/50 (0%)		2/21 (9.5%)
Voice Changes	0/50 (0%)		1/21 (4.8%)
Hypoxia	1/50 (2%)		0/21 (0%)
Fev1	1/50 (2%)		0/21 (0%)
Cough	13/50 (26%)		5/21 (23.8%)
Dlco	1/50 (2%)		0/21 (0%)
Pneumonitis	5/50 (10%)		3/21 (14.3%)
Pleural Effusion	2/50 (4%)		1/21 (4.8%)
Dyspnea	14/50 (28%)		13/21 (61.9%)
Skin and subcutaneous tissue disorders
Nail Changes	6/50 (12%)		2/21 (9.5%)
Hair Loss/Alopecia (Scalp Or Body)	3/50 (6%)		3/21 (14.3%)
Induration	0/50 (0%)		1/21 (4.8%)
Cheilitis	1/50 (2%)		1/21 (4.8%)
Wound Complication, Non-Infectious	1/50 (2%)		0/21 (0%)
Acne	2/50 (4%)		3/21 (14.3%)
Rash	27/50 (54%)		7/21 (33.3%)
Dry Skin	4/50 (8%)		3/21 (14.3%)
Pruritus	10/50 (20%)		3/21 (14.3%)
Burn	1/50 (2%)		0/21 (0%)
Flushing	2/50 (4%)		1/21 (4.8%)
Dermatology/Skin - Other	1/50 (2%)		5/21 (23.8%)
Ulceration	3/50 (6%)		2/21 (9.5%)
Vascular disorders
Inr	0/50 (0%)		1/21 (4.8%)
Ptt	1/50 (2%)		0/21 (0%)
Hemorrhage, Gu - Vagina	5/50 (10%)		0/21 (0%)
Hemorrhage, Gi - Varices (Rectal)	1/50 (2%)		0/21 (0%)
Hemorrhage, Gi - Upper Gi Nos	0/50 (0%)		1/21 (4.8%)
Hemorrhage/Pulmonary - Nose	3/50 (6%)		5/21 (23.8%)
Hemorrhage, Gu - Ureter	1/50 (2%)		0/21 (0%)
Petechiae	0/50 (0%)		1/21 (4.8%)
Hemorrhage/Bleeding - Other	2/50 (4%)		1/21 (4.8%)
Artery Injury - Extremity-Lower	0/50 (0%)		1/21 (4.8%)
Thrombosis/Embolism (Vascular Access-Related)	0/50 (0%)		1/21 (4.8%)
Thrombosis/Thrombus/Embolism	3/50 (6%)		5/21 (23.8%)
Phlebitis	0/50 (0%)		1/21 (4.8%)

Limitations/Caveats

The combination arm was closed after the first stage of accrual due to an excess of venous thromboses.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.