Bevacizumab and Temsirolimus in Treating Patients With Recurrent or Persistent Endometrial Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00723255
• Collaborator: NRG Oncology (Other)
• Enrollment: 53
• Locations: 41
• Arm: 1
• Duration (Months): 88.8
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial is studying the side effects of giving bevacizumab together with temsirolimus and to see how well it works in treating patients with recurrent or persistent endometrial cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. Giving bevacizumab together with temsirolimus may kill more tumor cells.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Endometrial Carcinoma	Biological: bevacizumab; Drug: temsirolimus	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess the activity of bevacizumab and temsirolimus, in terms of 6-month progression-free survival (PFS) and objective tumor response, in patients with recurrent or persistent endometrial cancer.

2. To determine the nature and degree of toxicity of this regimen in these patients.

SECONDARY OBJECTIVES:

1. To determine the duration of PFS and overall survival of patients treated with this regimen.

2. To determine the effects of prognostic factors (i.e., performance status, histological subtype, and grade) in patients treated with this regimen.

TERTIARY OBJECTIVES:

1. To compare the proportion of patients with objective tumor response and PFS at 6 months receiving the combination of bevacizumab and temsirolimus with those for the single agents bevacizumab and temsirolimus using historical controls.

OUTLINE: This is a multicenter study.

Patients receive bevacizumab IV on days 1 and 15 and temsirolimus IV on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months for 2 years, then every 6 months for 3 years, for a total of 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 53 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation of Combination Bevacizumab (NCI-Supplied Agent: NSC #70486) and Temsirolimus (CCI-779, NCI-Supplied Agent, NSC #683864) in the Treatment of Recurrent or Persistent Endometrial Carcinoma
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Jul 15, 2011
• Actual Study Completion Date: Jan 25, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (bevacizumab, temsirolimus) Patients receive bevacizumab IV on days 1 and 15 and temsirolimus IV on days 1, 8, 15, and 22.	Biological: bevacizumab; Given IV; Other Names: anti-VEGF humanized monoclonal antibody anti-VEGF monoclonal antibody Avastin rhuMAb VEGF ; Drug: temsirolimus; Given IV; Other Names: CCI-779 cell cycle inhibitor 779 Torisel

Outcome Measures

Primary Outcome Measures

1. Tumor Response [Scans are done while patient is on study therapy every other cycle for the first 6 months; then every 3 cycles thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease]

   Complete and Partial Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0

2. Progression-free Survival at 6 Months [Every other cycle for 6 months]

   Percentage of patients who are progression-free 6 months after study entry. Progression-Free Survival is the period from study entry until disease progression, death or date of last contact.

3. Frequency and Severity of Adverse Events Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 [Every cycle and 30 days after the last treatment, an average of 5 years.]

Secondary Outcome Measures

1. Progression-Free Survival [Scans are done while patient is on study therapy every other cycle for the first 6 months; then every 3 cycles thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease.]

   Progression-Free Survival is the period from study entry until disease progression, death or date of last contact.

2. Overall Survival [From entry into the study to death or the date of last contact, up to 5 years]

   The observed length of life from entry into the study to death or the date of last contact.

3. Complete and Partial Tumor Response by RECIST 1.0 by Performance Status [Scans are done while patient is on study therapy every other cycle for the first 6 months; then every 3 cycles thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease]

   Complete and Partial Tumor Response by RECIST 1.0

4. Progression-free Survival at 6 Months by Performance Status [Every other cycle for 6 months]

   Percentage of patients who are progression-free 6 months after study entry. Progression-Free Survival is the period from study entry until disease progression, death or date of last contact.

5. Complete and Partial Tumor Response by RECIST 1.0 by Histologic Type [Scans are done while patient is on study therapy every other cycle for the first 6 months; then every 3 cycles thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease]

   Complete and Partial Tumor Response by RECIST 1.0

6. Progression-free Survival at 6 Months by Histologic Type [Every other cycle for 6 months]

   Percentage of patients who are progression-free 6 months after study entry. Progression-Free Survival is the period from study entry until disease progression, death or date of last contact.

7. Complete and Partial Tumor Response by RECIST 1.0 by Tumor Grade [Scans are done while patient is on study therapy every other cycle for the first 6 months; then every 3 cycles thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease]

   Complete and Partial Tumor Response by RECIST 1.0

8. Progression-free Survival at 6 Months by Tumor Grade [Every other cycle for 6 months]

   Percentage of patients who are progression-free 6 months after study entry. Progression-Free Survival is the period from study entry until disease progression, death or date of last contact.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed endometrial carcinoma (from primary tumor) including any of the following cell types:

• Endometrioid adenocarcinoma

• Serous adenocarcinoma

• Undifferentiated carcinoma

• Clear cell adenocarcinoma

• Mixed epithelial carcinoma

• Adenocarcinoma not otherwise specified

• Mucinous adenocarcinoma

• Squamous cell carcinoma

• Transitional cell carcinoma

• Mesonephric carcinoma

• Recurrent or persistent disease that is refractory to curative therapy or established treatments

• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan

• Must have ≥ 1 target lesion to assess response as defined by RECIST

• Tumors within a previously irradiated field are designated as "non-target" lesions in the absence of documented disease progression or a biopsy to confirm persistence for ≥ 90 days after completion of radiotherapy

• Must have received 1 prior chemotherapeutic regimen for management of endometrial carcinoma

• May have received 1 additional cytotoxic regimen for management of this disease

• Not eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, including any active GOG Phase III protocol for patients with endometrial carcinoma

• No history or evidence of CNS disease, including primary brain tumor or any brain metastases upon physical examination

• GOG performance status (PS) 0-2 (for patients who have received 1 prior regimen) OR PS 0-1 (for patients who have received 2 prior regimens)

• ANC ≥ 1,500/mcL

• Platelet count ≥ 100,000/mcL

• Creatinine ≤ 1.5 times upper limit of normal (ULN)

• Bilirubin ≤ 1.5 times ULN

• SGOT ≤ 2.5 times ULN

• Alkaline phosphatase ≤ 2.5 times ULN

• Urine protein:creatinine ratio < 1.0 OR urine protein < 1,000 mg by 24-hour urine collection

• INR ≤ 1.5 OR in-range INR between 2 and 3 if patient is on a stable dose of therapeutic warfarin

• PTT ≤ 1.5 times ULN

• Fasting cholesterol < 350 mg/dL

• Fasting triglycerides < 400 mg/dL

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Seizures allowed provided they are controlled with standard medical therapy

• No active infection requiring antibiotics, except uncomplicated urinary tract infection

• No active bleeding or pathologic conditions that carry high risk of bleeding, (e.g., known bleeding disorder, coagulopathy, or tumor involving major vessels)

• No serious, non-healing wound, ulcer, or bone fracture, including abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 3 months

• No prior underlying lesions that caused the fistula or perforation that have not been corrected

• No prior interstitial pneumonitis

• No clinically significant cardiovascular disease, including any of the following:

• Uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or diastolic BP > 90 mm Hg

• Myocardial infarction or unstable angina within the past 6 months

• New York Heart Association class II-IV congestive heart failure

• Serious cardiac arrhythmia requiring medication

• Peripheral vascular disease ≥ grade 2

• No cerebrovascular accident, transient ischemic attack, or subarachnoid hemorrhage within the past 6 months

• No uncontrolled diabetes

• Hemoglobin A1C < 10

• No other invasive malignancies within the past 5 years, except nonmelanoma skin cancer and other specific malignancies (e.g., localized breast, head and neck, or skin cancer that completed treatment > 3 years prior to study and remain disease-free)

• No significant traumatic injury within the past 28 days

• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies

• Concurrent prophylactic or therapeutic anticoagulation* (e.g., warfarin) allowed

• Recovered from recent surgery, radiotherapy, or chemotherapy

• No prior bevacizumab or other VEGF pathway-targeted therapy

• No prior temsirolimus, everolimus, deforolimus, sirolimus, or any other mTor/PI3K pathway-targeted therapy

• No prior non-cytotoxic chemotherapy for management of this disease, except hormonal therapy

• At least 1 week since prior hormonal therapy directed at the malignant tumor

• No prior therapy that contraindicates this protocol therapy

• No prior radiotherapy to any portion of the abdominal cavity or pelvis within the past 5 years, except treatment of endometrial cancer

• Prior radiotherapy for localized cancer of the breast, head and neck, or skin is allowed, provided it was completed > 3 years prior to study entry and patient remains free of recurrent or metastatic disease

• No prior chemotherapy for any abdominal or pelvic tumor within the past 5 years, except treatment of endometrial cancer

• Prior adjuvant chemotherapy for localized breast cancer allowed, provided it was completed > 3 years prior to study entry and the patient remains free of recurrent or metastatic disease

• Prior treatment with an anthracycline (i.e., doxorubicin and/or liposomal doxorubicin) allowed provided ejection fraction < 50%

• More than 28 days since prior major surgery or open biopsy

• More than 7 days since minor surgical procedures, fine needle aspirates, or core biopsies

• At least 3 weeks since prior therapy directed at the malignant tumor, including immunologic agents

• No concurrent major surgery

• No concurrent prophylactic filgrastim (G-CSF) or thrombopoietic agents

• No concurrent amifostine or other protective reagents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hartford Hospital	Hartford	Connecticut	United States	06102
2	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
3	Washington Hospital Center	Washington	District of Columbia	United States	20010
4	Memorial University Medical Center	Savannah	Georgia	United States	31404
5	Rush University Medical Center	Chicago	Illinois	United States	60612
6	University of Chicago	Chicago	Illinois	United States	60637
7	Sudarshan K Sharma MD Limted-Gynecologic Oncology	Hinsdale	Illinois	United States	60521
8	Elkhart General Hospital	Elkhart	Indiana	United States	46515
9	Indiana University Medical Center	Indianapolis	Indiana	United States	46202
10	Saint Vincent Hospital and Health Services	Indianapolis	Indiana	United States	46260
11	Community Howard Regional Health	Kokomo	Indiana	United States	46904
12	IU Health La Porte Hospital	La Porte	Indiana	United States	46350
13	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana	United States	46545-1470
14	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
15	South Bend Clinic	South Bend	Indiana	United States	46617
16	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46628
17	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
18	Gynecologic Oncology of West Michigan PLLC	Grand Rapids	Michigan	United States	49546
19	Lakeland Hospital	Saint Joseph	Michigan	United States	49085
20	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
21	Centerpoint Medical Center LLC	Independence	Missouri	United States	64057
22	Truman Medical Center	Kansas City	Missouri	United States	64108
23	Saint Louis University Hospital	Saint Louis	Missouri	United States	63110
24	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
25	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
26	Ozark Health Ventures LLC-Cancer Research for The Ozarks Springfield	Springfield	Missouri	United States	65804
27	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
28	Women's Cancer Care Associates LLC	Albany	New York	United States	12208
29	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
30	Carolinas Medical Center	Charlotte	North Carolina	United States	28203
31	Gynecologic Oncology Network	Greenville	North Carolina	United States	27834
32	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
33	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
34	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
35	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
36	Tulsa Cancer Institute	Tulsa	Oklahoma	United States	74146
37	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
38	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
39	Women and Infants Hospital	Providence	Rhode Island	United States	02905
40	AnMed Health Cancer Center	Anderson	South Carolina	United States	29621
41	Carilion Clinic Gynecological Oncology	Roanoke	Virginia	United States	24016

Sponsors and Collaborators

• National Cancer Institute (NCI)
• NRG Oncology

Investigators

• Principal Investigator: Edwin Alvarez, Gynecologic Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00723255
• Other Study ID Numbers: NCI-2009-00598; NCI-2009-00598; CDR0000601291; GOG-0229G; GOG-0229G; U10CA027469
• First Posted: Jul 28, 2008
• Last Update Posted: Jul 23, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Carcinoma; Endometrial Neoplasms; Recurrence; Sirolimus; Bevacizumab; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal

Study Results

Participant Flow

Recruitment Details	The study was activated on 9/8/2008 and closed to accrual on 3/22/2010 (and was suspended from 1/19/2009 to 12/7/2009).

Arm/Group Title	Bevacizumab Plus Temsirolimus
Arm/Group Description	Bevacizumab 10 mg/kg IV every other week plus Temsirolimus 25 mg IV weekly (one cycle = 4 weeks) until disease progression or adverse effects prohibit further therapy
Period Title: Overall Study
STARTED	53
COMPLETED	49
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Bevacizumab Plus Temsirolimus
Arm/Group Description	Bevacizumab 10 mg/kg IV every other week plus Temsirolimus 25 mg IV weekly (one cycle = 4 weeks) until disease progression or adverse effects prohibit further therapy
Overall Participants	49
Age, Customized (participants) [Number]
20-29 years	0 0%
30-39 years	1 2%
40-49 years	4 8.2%
50-59 years	11 22.4%
60-69 years	21 42.9%
70-79 years	11 22.4%
80-89 years	1 2%
Sex: Female, Male (Count of Participants)
Female	49 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Tumor Response
Description	Complete and Partial Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0
Time Frame	Scans are done while patient is on study therapy every other cycle for the first 6 months; then every 3 cycles thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease

Outcome Measure Data

Analysis Population Description

Eligible and Treated Patients

Arm/Group Title	Bevacizumab Plus Temsirolimus
Arm/Group Description	Bevacizumab 10 mg/kg IV every other week plus Temsirolimus 25 mg IV weekly (one cycle = 4 weeks) until disease progression or adverse effects prohibit further therapy
Measure Participants	49
Number (90% Confidence Interval) [percentage of participants]	24.5 50%

2. Primary Outcome

Title	Progression-free Survival at 6 Months
Description	Percentage of patients who are progression-free 6 months after study entry. Progression-Free Survival is the period from study entry until disease progression, death or date of last contact.
Time Frame	Every other cycle for 6 months

Outcome Measure Data

Analysis Population Description

Eligible and Treated Patients

Arm/Group Title	Bevacizumab Plus Temsirolimus
Arm/Group Description	Bevacizumab 10 mg/kg IV every other week plus Temsirolimus 25 mg IV weekly (one cycle = 4 weeks) until disease progression or adverse effects prohibit further therapy
Measure Participants	49
Number (90% Confidence Interval) [percentage of participants]	46.9 95.7%

3. Primary Outcome

Title	Frequency and Severity of Adverse Events Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
Time Frame	Every cycle and 30 days after the last treatment, an average of 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients

Arm/Group Title	Grade 0	Grade 1 (CTCAE v 3.0)	Grade 2 (CTCAE v 3.0)	Grade 3 (CTCAE v 3.0)	Grade 4 (CTCAE v 3.0)	Grade 5 (CTCAE v 3.0)
Arm/Group Description	Number of patients who did not experience the specified AE.	Number of patients who experienced a grade 1 event using Common Terminology Criteria version 3.0	Number of patients who experienced a grade 2 event using Common Terminology Criteria version 3.0	Number of patients who experienced a grade 3 event using Common Terminology Criteria version 3.0	Number of patients who experienced a grade 4 event using Common Terminology Criteria version 3.0	Number of patients who experienced a grade 5 event using Common Terminology Criteria version 3.0
Measure Participants	49	49	49	49	49	49
Leukopenia	20 40.8%	13 NaN	15 NaN	1 NaN	0 NaN	0 NaN
Thrombocytopenia	24 49%	18 NaN	4 NaN	3 NaN	0 NaN	0 NaN
Neutropenia	28 57.1%	7 NaN	9 NaN	5 NaN	0 NaN	0 NaN
Anemia	14 28.6%	17 NaN	14 NaN	3 NaN	1 NaN	0 NaN
Other hematologic	46 93.9%	1 NaN	2 NaN	0 NaN	0 NaN	0 NaN
Allergy/immunology	47 95.9%	1 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Cardiac	33 67.3%	3 NaN	7 NaN	5 NaN	1 NaN	0 NaN
Coagulation	48 98%	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN
Constitutional	12 24.5%	9 NaN	18 NaN	9 NaN	1 NaN	0 NaN
Dermatologic	18 36.7%	13 NaN	16 NaN	2 NaN	0 NaN	0 NaN
Endocrine	48 98%	1 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Gastrointestinal	5 10.2%	11 NaN	15 NaN	17 NaN	1 NaN	0 NaN
Genitourinary/renal	44 89.8%	3 NaN	1 NaN	1 NaN	0 NaN	0 NaN
Hemorrhage	25 51%	22 NaN	1 NaN	1 NaN	0 NaN	0 NaN
Infection	34 69.4%	0 NaN	8 NaN	6 NaN	0 NaN	1 NaN
Lymphatics	40 81.6%	5 NaN	3 NaN	1 NaN	0 NaN	0 NaN
Metabolic	9 18.4%	11 NaN	12 NaN	14 NaN	3 NaN	0 NaN
Musculoskeletal	43 87.8%	3 NaN	2 NaN	1 NaN	0 NaN	0 NaN
Neurosensory	43 87.8%	5 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Other neurological	41 83.7%	4 NaN	3 NaN	1 NaN	0 NaN	0 NaN
Ocular/visual	45 91.8%	2 NaN	1 NaN	1 NaN	0 NaN	0 NaN
Pain	18 36.7%	12 NaN	10 NaN	8 NaN	1 NaN	0 NaN
Pulmonary	26 53.1%	14 NaN	7 NaN	1 NaN	0 NaN	1 NaN
Sexual/reproductive	48 98%	1 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Vascular	47 95.9%	0 NaN	0 NaN	1 NaN	1 NaN	0 NaN
Death, not CTC coded	48 98%	0 NaN	0 NaN	0 NaN	0 NaN	1 NaN

4. Secondary Outcome

Title	Progression-Free Survival
Description	Progression-Free Survival is the period from study entry until disease progression, death or date of last contact.
Time Frame	Scans are done while patient is on study therapy every other cycle for the first 6 months; then every 3 cycles thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease.

Outcome Measure Data

Analysis Population Description

Eligible and Treated Patients

Arm/Group Title	Bevacizumab Plus Temsirolimus
Arm/Group Description	Bevacizumab 10 mg/kg IV every other week plus Temsirolimus 25 mg IV weekly (one cycle = 4 weeks) until disease progression or adverse effects prohibit further therapy
Measure Participants	49
Median (95% Confidence Interval) [Months]	5.6

5. Secondary Outcome

Title	Overall Survival
Description	The observed length of life from entry into the study to death or the date of last contact.
Time Frame	From entry into the study to death or the date of last contact, up to 5 years

Outcome Measure Data

Analysis Population Description

Eligible and Treated Patients

Arm/Group Title	Bevacizumab Plus Temsirolimus
Arm/Group Description	Bevacizumab 10 mg/kg IV every other week plus Temsirolimus 25 mg IV weekly (one cycle = 4 weeks) until disease progression or adverse effects prohibit further therapy
Measure Participants	49
Median (95% Confidence Interval) [Months]	16.9

6. Secondary Outcome

Title	Complete and Partial Tumor Response by RECIST 1.0 by Performance Status
Description	Complete and Partial Tumor Response by RECIST 1.0
Time Frame	Scans are done while patient is on study therapy every other cycle for the first 6 months; then every 3 cycles thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Performance Status 0	Performance Status 1,2
Arm/Group Description	Patients with performance status 0 Performance Status 0: Fully active, able to carry on all pre-disease performance without restriction	Patients with performance status 1 or 2 Performance Status 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light house work Performance Status 2: Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours
Measure Participants	29	20
Number (95% Confidence Interval) [percentage of participants]	24 49%	25 NaN

7. Secondary Outcome

Title	Progression-free Survival at 6 Months by Performance Status
Description	Percentage of patients who are progression-free 6 months after study entry. Progression-Free Survival is the period from study entry until disease progression, death or date of last contact.
Time Frame	Every other cycle for 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Performance Status 0	Performance Status 1,2
Arm/Group Description	Patients with performance status 0 Performance Status 0: Fully active, able to carry on all pre-disease performance without restriction	Patients with performance status 1 or 2 Performance Status 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light house work Performance Status 2: Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours
Measure Participants	29	20
Number (95% Confidence Interval) [percentage of participants]	48 98%	45 NaN

8. Secondary Outcome

Title	Complete and Partial Tumor Response by RECIST 1.0 by Histologic Type
Description	Complete and Partial Tumor Response by RECIST 1.0
Time Frame	Scans are done while patient is on study therapy every other cycle for the first 6 months; then every 3 cycles thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Endometrioid Adenocarcinoma	Other Histologic Types
Arm/Group Description	Patients with endometrioid adenocarcinoma	Patients with other histologic types, including benign (not otherwise specified) (n=1), unspecified adenocarcinoma (n=1), clear cell carcinoma (n=2), mucinous adenocarcinoma (n=1), mixed epithelial carcinoma (n=5), undifferentiated carcinoma (n=1), serous adenocarcinoma (n=4)
Measure Participants	34	15
Number (95% Confidence Interval) [percentage of participants]	21 42.9%	33 NaN

9. Secondary Outcome

Title	Progression-free Survival at 6 Months by Histologic Type
Description	Percentage of patients who are progression-free 6 months after study entry. Progression-Free Survival is the period from study entry until disease progression, death or date of last contact.
Time Frame	Every other cycle for 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Endometrioid Adenocarcinoma	Other Histologic Types
Arm/Group Description	Patients with endometrioid adenocarcinoma	Patients with other histologic types, including benign (not otherwise specified) (n=1), unspecified adenocarcinoma (n=1), clear cell carcinoma (n=2), mucinous adenocarcinoma (n=1), mixed epithelial carcinoma (n=5), undifferentiated carcinoma (n=1), serous adenocarcinoma (n=4)
Measure Participants	34	15
Number (95% Confidence Interval) [percentage of participants]	44 89.8%	53 NaN

10. Secondary Outcome

Title	Complete and Partial Tumor Response by RECIST 1.0 by Tumor Grade
Description	Complete and Partial Tumor Response by RECIST 1.0
Time Frame	Scans are done while patient is on study therapy every other cycle for the first 6 months; then every 3 cycles thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Grade 1,2	Grade 3
Arm/Group Description	Patients with grade 1-2 tumors (patients with missing grade excluded, n=7)	Patients with grade 3 tumors (patients with missing grade excluded, n=7)
Measure Participants	20	15
Number (95% Confidence Interval) [percentage of participants]	30 61.2%	18 NaN

11. Secondary Outcome

Title	Progression-free Survival at 6 Months by Tumor Grade
Description	Percentage of patients who are progression-free 6 months after study entry. Progression-Free Survival is the period from study entry until disease progression, death or date of last contact.
Time Frame	Every other cycle for 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Grade 1,2	Grade 3
Arm/Group Description	Patients with grade 1-2 tumors (patients with missing grade excluded, n=7)	Patients with grade 3 tumors (patients with missing grade excluded, n=7)
Measure Participants	20	15
Number (95% Confidence Interval) [percentage of participants]	60 122.4%	32 NaN

Adverse Events

Time Frame	All Adverse Events (AEs) during treatment (up to 30 days after treatment completion). All Serious Adverse Events (SAEs) up to 30 days after treatment completion and considered to be treatment related between 30 days and 5 years after treatment completion.
Arm/Group Title	Bevacizumab Plus Temsirolimus
Arm/Group Description	Bevacizumab 10 mg/kg IV every other week plus Temsirolimus 25 mg IV weekly (one cycle = 4 weeks) until disease progression or adverse effects prohibit further therapy
All Cause Mortality
	Bevacizumab Plus Temsirolimus
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Bevacizumab Plus Temsirolimus
	Affected / at Risk (%)	# Events
Total	31/49 (63.3%)
Cardiac disorders
Hypertension	1/49 (2%)
Lt Ventricular Systolic Dysfunction	1/49 (2%)
Gastrointestinal disorders
Fistula, Gi - Rectum	1/49 (2%)
Obstruction, Gi - Colon	1/49 (2%)
Ileus	1/49 (2%)
Obstruction, Gi - Small Bowel Nos	2/49 (4.1%)
Perforation, Gi - Small Bowel Nos	1/49 (2%)
Vomiting	2/49 (4.1%)
Anorexia	1/49 (2%)
Constipation	4/49 (8.2%)
Nausea	1/49 (2%)
General disorders
Fever	1/49 (2%)
Death No Ctcae Term - Sudden Death	2/49 (4.1%)
Pain: Neck	1/49 (2%)
Pain: Rectum	2/49 (4.1%)
Pain: Abdominal Pain Nos	1/49 (2%)
Infections and infestations
Inf W/Nml Or Gr 1 Or 2 Anc: Lung(Pneumonia)	1/49 (2%)
Inf W/Nml Or Gr 1 Or 2 Anc: Skin(Cellulitis)	1/49 (2%)
Inf W/Nml Or Gr 1 Or 2 Anc: Dental-Tooth	1/49 (2%)
Inf W/Nml Or Gr 1 Or 2 Anc: Urinary Tract Nos	1/49 (2%)
Metabolism and nutrition disorders
Proteinuria	1/49 (2%)
Hypertriglyceridemia	1/49 (2%)
Hypercalcemia	1/49 (2%)
Hypomagnesemia	1/49 (2%)
Musculoskeletal and connective tissue disorders
Muscle Weakness - Whole Body/Generalized	1/49 (2%)
Renal and urinary disorders
Obstruction, Gu - Ureter	1/49 (2%)
Fistula, Gu - Vagina	1/49 (2%)
Renal Failure	1/49 (2%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis	1/49 (2%)
Vascular disorders
Inr	1/49 (2%)
Hemorrhage/Pulmonary - Nose	1/49 (2%)
Thrombosis/Embolism (Vascular Access-Related)	1/49 (2%)
Other (Not Including Serious) Adverse Events
	Bevacizumab Plus Temsirolimus
	Affected / at Risk (%)	# Events
Total	49/49 (100%)
Blood and lymphatic system disorders
Neutrophils	23/49 (46.9%)
Platelets	27/49 (55.1%)
Leukocytes	29/49 (59.2%)
Lymphopenia	3/49 (6.1%)
Hemoglobin	39/49 (79.6%)
Edema: Limb	11/49 (22.4%)
Edema: Head And Neck	2/49 (4.1%)
Cardiac disorders
Palpitations	2/49 (4.1%)
S/N Arrhythmia: Sinus Tachycardia	4/49 (8.2%)
Vasovagal Episode	1/49 (2%)
Hypertension	15/49 (30.6%)
Restrictive Cardiomyopathy	1/49 (2%)
Cardiac General - Other	1/49 (2%)
Pericardial Effusion	1/49 (2%)
Hypotension	2/49 (4.1%)
Ear and labyrinth disorders
Tinnitus	4/49 (8.2%)
Endocrine disorders
Hot Flashes	4/49 (8.2%)
Hypothyroidism	1/49 (2%)
Eye disorders
Watery Eye	2/49 (4.1%)
Cataract	1/49 (2%)
Flashing Lights/Floaters	3/49 (6.1%)
Blurred Vision	8/49 (16.3%)
Gastrointestinal disorders
Proctitis	1/49 (2%)
Flatulence	1/49 (2%)
Fistula, Gi - Rectum	1/49 (2%)
Ulcer,gi - Stoma	2/49 (4.1%)
Hemorrhoids	4/49 (8.2%)
Heartburn	2/49 (4.1%)
Mucositis (Functional/Sympt) - Pharynx	1/49 (2%)
Dysphagia	6/49 (12.2%)
Distention	1/49 (2%)
Taste Alteration	10/49 (20.4%)
Incontinence, Anal	1/49 (2%)
Dry Mouth	1/49 (2%)
Mucositis (Functional/Sympt) - Oral Cavity	16/49 (32.7%)
Mucositis (Clinical Exam) - Stomach	1/49 (2%)
Perforation, Gi - Small Bowel Nos	2/49 (4.1%)
Mucositis (Clinical Exam) - Oral Cavity	17/49 (34.7%)
Mucositis (Clinical Exam) - Anus	2/49 (4.1%)
Vomiting	20/49 (40.8%)
Anorexia	21/49 (42.9%)
Dehydration	6/49 (12.2%)
Constipation	20/49 (40.8%)
Nausea	29/49 (59.2%)
Diarrhea	29/49 (59.2%)
General disorders
Constitutional Symptoms - Other	1/49 (2%)
Fever	7/49 (14.3%)
Weight Loss	16/49 (32.7%)
Rigors/Chills	2/49 (4.1%)
Fatigue	38/49 (77.6%)
Insomnia	5/49 (10.2%)
Death No Ctcae Term - Disease Progression Nos	2/49 (4.1%)
Pain: Urethra	1/49 (2%)
Pain: Perineum	1/49 (2%)
Pain: Pelvis	1/49 (2%)
Pain: Vagina	1/49 (2%)
Pain: Chest Wall	1/49 (2%)
Pain: Throat/Pharynx/Larynx	3/49 (6.1%)
Pain: Larynx	1/49 (2%)
Pain: Head/Headache	15/49 (30.6%)
Pain: Extremity-Limb	7/49 (14.3%)
Pain: Back	4/49 (8.2%)
Pain: Joint	12/49 (24.5%)
Pain: Bone	3/49 (6.1%)
Pain: Bladder	3/49 (6.1%)
Pain: Pain Nos	1/49 (2%)
Pain: Stomach	1/49 (2%)
Pain: Rectum	3/49 (6.1%)
Pain: Oral Cavity	2/49 (4.1%)
Pain: Dental/Teeth/Peridontal	1/49 (2%)
Pain: Abdominal Pain Nos	17/49 (34.7%)
Pain: Scalp	1/49 (2%)
Pain: Oral - Gums	1/49 (2%)
Pain: Middle Ear	3/49 (6.1%)
Pain: External Ear	1/49 (2%)
Pain: Face	1/49 (2%)
Pain: Muscle	3/49 (6.1%)
Pain: Anus	1/49 (2%)
Flu-Like Syndrome	1/49 (2%)
Immune system disorders
Allergic Reaction/Hypersensitivity	2/49 (4.1%)
Rhinitis	3/49 (6.1%)
Infections and infestations
Inf W/Nml Or Gr 1 Or 2 Anc: Nose	2/49 (4.1%)
Inf W/Nml Or Gr 1 Or 2 Anc: Lung(Pneumonia)	2/49 (4.1%)
Inf W/Nml Or Gr 1 Or 2 Anc: Skin(Cellulitis)	3/49 (6.1%)
Inf W/Nml Or Gr 1 Or 2 Anc: Dental-Tooth	1/49 (2%)
Inf W/Nml Or Gr 1 Or 2 Anc: Urinary Tract Nos	7/49 (14.3%)
Inf W/Nml Or Gr 1 Or 2 Anc: Abdomen Nos	2/49 (4.1%)
Inf W/Nml Or Gr 1 Or 2 Anc: Ungual (Nails)	1/49 (2%)
Infection - Other	1/49 (2%)
Inf W/Nml Or Gr 1 Or 2 Anc: Bronchus	1/49 (2%)
Inf W/Nml Or Gr 1 Or 2 Anc: Sinus	2/49 (4.1%)
Inf Unknown Anc: External Ear	1/49 (2%)
Inf W/Nml Or Gr 1 Or 2 Anc: Bladder	3/49 (6.1%)
Metabolism and nutrition disorders
Ast	14/49 (28.6%)
Gfr	2/49 (4.1%)
Cholesterol,serum High	28/49 (57.1%)
Proteinuria	1/49 (2%)
Creatinine	10/49 (20.4%)
Hypoalbuminemia	10/49 (20.4%)
Alt	13/49 (26.5%)
Alkaline Phosphatase	5/49 (10.2%)
Bilirubin	2/49 (4.1%)
Lipase	1/49 (2%)
Hypophosphatemia	12/49 (24.5%)
Hyponatremia	12/49 (24.5%)
Hypertriglyceridemia	27/49 (55.1%)
Cpk	1/49 (2%)
Bicarbonate, Serum-Low	1/49 (2%)
Hypernatremia	4/49 (8.2%)
Hypocalcemia	14/49 (28.6%)
Hyperkalemia	1/49 (2%)
Hyperglycemia	20/49 (40.8%)
Hypokalemia	17/49 (34.7%)
Hypoglycemia	2/49 (4.1%)
Hypomagnesemia	12/49 (24.5%)
Musculoskeletal and connective tissue disorders
Fibrosis-Deep Connective Tissue	1/49 (2%)
Joint Effusion	1/49 (2%)
Fracture	1/49 (2%)
Arthritis	2/49 (4.1%)
Muscle Weakness - Whole Body/Generalized	9/49 (18.4%)
Muscle Weakness - Extremity-Lower	5/49 (10.2%)
Nervous system disorders
Mood Alteration - Depression	7/49 (14.3%)
Mood Alteration - Anxiety	2/49 (4.1%)
Tremor	1/49 (2%)
Somnolence	1/49 (2%)
Cognitive Disturbance	1/49 (2%)
Confusion	2/49 (4.1%)
Memory Impairment	2/49 (4.1%)
Dizziness	6/49 (12.2%)
Neuropathy-Sensory	18/49 (36.7%)
Neuropathy-Motor	2/49 (4.1%)
Renal and urinary disorders
Cystitis	1/49 (2%)
Urinary Retention	1/49 (2%)
Obstruction, Gu - Ureter	1/49 (2%)
Incontinence, Urinary	1/49 (2%)
Fistula, Gu - Vagina	1/49 (2%)
Bladder Spasm	1/49 (2%)
Urinary Frequency	9/49 (18.4%)
Reproductive system and breast disorders
Vaginitis	1/49 (2%)
Vaginal Discharge	1/49 (2%)
Respiratory, thoracic and mediastinal disorders
Pulmonary: Other	1/49 (2%)
Nasal/Paranasal Reactions	3/49 (6.1%)
Voice Changes	4/49 (8.2%)
Hypoxia	1/49 (2%)
Cough	18/49 (36.7%)
Pneumonitis	3/49 (6.1%)
Dyspnea	18/49 (36.7%)
Skin and subcutaneous tissue disorders
Nail Changes	10/49 (20.4%)
Hair Loss/Alopecia (Scalp Or Body)	12/49 (24.5%)
Bruising	4/49 (8.2%)
Acne	5/49 (10.2%)
Rash	24/49 (49%)
Dry Skin	1/49 (2%)
Decubitus	1/49 (2%)
Pruritus	10/49 (20.4%)
Burn	1/49 (2%)
Flushing	3/49 (6.1%)
Hyperpigmentation	3/49 (6.1%)
Ulceration	3/49 (6.1%)
Vascular disorders
Inr	1/49 (2%)
Ptt	1/49 (2%)
Hemorrhage, Gu - Urinary Nos	3/49 (6.1%)
Hemorrhage, Gu - Vagina	3/49 (6.1%)
Hemorrhage, Gi - Rectum	7/49 (14.3%)
Hemorrhage/Pulmonary - Nose	23/49 (46.9%)
Hematoma	1/49 (2%)
Hemorrhage, Gi - Anus	1/49 (2%)
Hemorrhage, Gi - Colon	1/49 (2%)
Thrombosis/Thrombus/Embolism	2/49 (4.1%)

Limitations/Caveats

[Not Specified]

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.