Paclitaxel, Carboplatin, and Bevacizumab or Paclitaxel, Carboplatin, and Temsirolimus or Ixabepilone, Carboplatin, and Bevacizumab in Treating Patients With Stage III, Stage IV, or Recurrent Endometrial Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00977574
• Collaborator: NRG Oncology (Other)
• Enrollment: 349
• Locations: 233
• Arms: 3
• Patients Per Site: 1.5

Study Details

Study Description

Brief Summary

This randomized phase II trial studies paclitaxel, carboplatin, and bevacizumab or paclitaxel, carboplatin, and temsirolimus or ixabepilone, carboplatin, and bevacizumab to see how well they work in treating patients with stage III, stage IV, or recurrent endometrial cancer. Drugs used in chemotherapy, such as paclitaxel, carboplatin, and ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known which treatment regimen is most effective in treating patients with endometrial cancer.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Cancer; Stage IIIA Uterine Corpus Cancer AJCC v7; Stage IIIB Uterine Corpus Cancer AJCC v7; Stage IIIC Uterine Corpus Cancer AJCC v7; Stage IVA Uterine Corpus Cancer AJCC v7; Stage IVB Uterine Corpus Cancer AJCC v7	Biological: Bevacizumab; Drug: Carboplatin; Drug: Ixabepilone; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Drug: Temsirolimus	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To estimate the hazard of progression or death of each of the three arms relative to that of historical controls in patients with advanced or recurrent endometrial cancer.

SECONDARY OBJECTIVES:

1. To determine the nature, frequency, and maximum degree of toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v)3.0 for each of the three arms.

2. To estimate the distribution of the duration of overall survival for each of the three arms.

3. To estimate the proportion of patients with measurable disease who have confirmed objective tumor responses by treatment.

TERTIARY OBJECTIVES:

1. Explore the associations between select biomarkers and progression-free survival as well as secondary measures of clinical outcome (overall survival, tumor response, or disease status if possible) in the context of histologic cell type and treatment.

IA. Somatic mutations in phosphatase and tensin homolog (PTEN)/ phosphoinositide-3-kinase (PI3K) and RAS pathway members by Sequenom mutational profiling and targeted sequencing of candidate genes.

IB. Microsatellite instability by analysis of five National Cancer Institute consensus microsatellite markers (BAT25, BAT26, D2S2123, D5S346, and D17S250) using the Applied Biosystems (ABI) Prism 3100 Genetic Analyzer.

IC. Copy number alterations (gains or losses) by array comparative genomic hybridization (aCGH).

ID. Tumor expression of PTEN and class III beta-tubulin using immunohistochemistry.

IE. Concentration of vascular endothelial growth factor (VEGF) in pre-cycle 1 plasma using an enzyme-linked immunosorbent assay.

1. Explore the relationship among the various biomarkers by histologic subtype and treatment.

2. Explore which combination of biomarkers and clinical covariates optimally predicts responsiveness and resistance to the three treatment arms.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours, carboplatin IV over 30 minutes, and bevacizumab* IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients undergoing treatment post-surgery (=< 12 weeks) receive bevacizumab beginning on course 2.

ARM II: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus* IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive temsirolimus IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients undergoing treatment post-surgery (=< 12 weeks) receive temsirolimus beginning on course 2.

ARM III: Patients receive ixabepilone IV over 1 hour, carboplatin IV over 30 minutes, and bevacizumab* IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients undergoing treatment post-surgery (=< 12 weeks) receive bevacizumab beginning on course 2.

After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 349 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Three Arm Randomized Phase II Study of Paclitaxel/Carboplatin/Bevacizumab (NSC #704865), Paclitaxel/Carboplatin/Temsirolimus (NSC #683864) and Ixabepilone (NSC #710428)/Carboplatin/Bevacizumab as Initial Therapy for Measurable Stage III or IVA, Stage IVB, or Recurrent Endometrial Cancer
• Actual Study Start Date: Sep 14, 2009
• Actual Primary Completion Date: Jan 31, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (paclitaxel, carboplatin, bevacizumab) Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Biological: Bevacizumab; Given IV; Other Names: ABP 215 Anti-VEGF Anti-VEGF Humanized Monoclonal Antibody Anti-VEGF Monoclonal Antibody SIBP04 Anti-VEGF rhuMAb Avastin Bevacizumab awwb Bevacizumab Biosimilar ABP 215 Bevacizumab Biosimilar BEVZ92 Bevacizumab Biosimilar BI 695502 Bevacizumab Biosimilar CBT 124 Bevacizumab Biosimilar CT-P16 Bevacizumab Biosimilar FKB238 Bevacizumab Biosimilar GB-222 Bevacizumab Biosimilar HD204 Bevacizumab Biosimilar HLX04 Bevacizumab Biosimilar IBI305 Bevacizumab Biosimilar LY01008 Bevacizumab Biosimilar MIL60 Bevacizumab Biosimilar Mvasi Bevacizumab Biosimilar MYL-1402O Bevacizumab Biosimilar QL 1101 Bevacizumab Biosimilar RPH-001 Bevacizumab Biosimilar SCT501 Bevacizumab Biosimilar Zirabev Bevacizumab-awwb Bevacizumab-bvzr BP102 BP102 Biosimilar HD204 Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer Mvasi MYL-1402O Recombinant Humanized Anti-VEGF Monoclonal Antibody rhuMab-VEGF SCT501 SIBP 04 SIBP-04 SIBP04 Zirabev ; Drug: Carboplatin; Given IV; Other Names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Paclitaxel; Given IV; Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat
Experimental: Arm II (paclitaxel, carboplatin, temsirolimus) Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: Carboplatin; Given IV; Other Names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Paclitaxel; Given IV; Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat ; 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 III (ixabepilone, carboplatin, bevacizumab) Patients receive ixabepilone IV over 1 hour, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Biological: Bevacizumab; Given IV; Other Names: ABP 215 Anti-VEGF Anti-VEGF Humanized Monoclonal Antibody Anti-VEGF Monoclonal Antibody SIBP04 Anti-VEGF rhuMAb Avastin Bevacizumab awwb Bevacizumab Biosimilar ABP 215 Bevacizumab Biosimilar BEVZ92 Bevacizumab Biosimilar BI 695502 Bevacizumab Biosimilar CBT 124 Bevacizumab Biosimilar CT-P16 Bevacizumab Biosimilar FKB238 Bevacizumab Biosimilar GB-222 Bevacizumab Biosimilar HD204 Bevacizumab Biosimilar HLX04 Bevacizumab Biosimilar IBI305 Bevacizumab Biosimilar LY01008 Bevacizumab Biosimilar MIL60 Bevacizumab Biosimilar Mvasi Bevacizumab Biosimilar MYL-1402O Bevacizumab Biosimilar QL 1101 Bevacizumab Biosimilar RPH-001 Bevacizumab Biosimilar SCT501 Bevacizumab Biosimilar Zirabev Bevacizumab-awwb Bevacizumab-bvzr BP102 BP102 Biosimilar HD204 Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer Mvasi MYL-1402O Recombinant Humanized Anti-VEGF Monoclonal Antibody rhuMab-VEGF SCT501 SIBP 04 SIBP-04 SIBP04 Zirabev ; Drug: Carboplatin; Given IV; Other Names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo ; Drug: Ixabepilone; Given IV; Other Names: (1S,3S,7S,10R,11S,12S,16R)-7,11-Dihydroxy-8,8,10,12,16-pentamethyl-3-[(1E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-17-oxa-4-azabicyclo[14.1.0]heptadecane-5,9-dione Azaepothilone B BMS 247550 BMS-247550 BMS247550 Epothilone Epothilone-B BMS 247550 Ixempra ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Progressed or Died by 25 Months From Enrollment [at 25 months]

   PFS (Progression free survival) is defined as the duration of time from date of study entry to time of progression or death, whichever occurs first. Patients with a status of alive, progression-free are censored at their date of last follow-up. To lessen the potential for bias in the progression evaluation times between treatment arms and historical controls, progression/death times will be grouped over 6 18-week time intervals. Progressions are carried forward to the end of the interval. All progressions or deaths occurring after the 6th 18-week interval are censored at 25 months for this analysis. Study NCT00977574

Secondary Outcome Measures

1. Frequency and Severity of Toxicity as Assessed by CTCAE v3.0 for Each of the Three Arms. [Median of 10 cycles of treatment plus 30 days]

2. The Median Duration of Overall Survival for Each of the Three Arms. [Time from date of study entry to time of death or the date of last contact, assessed up to 5 years]

   Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.

3. The Proportion of Patients With Measurable Disease Who Have Confirmed Objective Tumor Responses by Treatment. [Imaging was done every 3 cycles and at any other time clinically indicated. Imaging was required every 9 weeks until progression or initiation on non protocol therapy. After 2 years of protocol therapy or follow up, CT scan or MRI was every 3 months]

   RECIST 1.1 was used to define objective tumor response. A complete response is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. A partial response is defined as At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. There can be no unequivocal progression of non-target lesions and no new lesions. Complete and partial responses are included in the objective tumor response rate. Confirmation of response was not required.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have measurable stage III, measurable stage IVA, stage IVB (with or without measurable disease) or recurrent (with or without measurable disease) endometrial carcinoma

• Histologic confirmation of the original primary tumor is required; patients with the following histologic epithelial cell types are eligible: endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma

• Measurable disease is defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1); measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI

• Patients must have Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2

• Patients must not be eligible for a higher priority GOG protocol, if one exists; in general, this would refer to any active GOG Phase III protocol or Rare Tumor protocol for the same patient population

• Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl equivalent to Common Terminology Criteria (CTCAE v3.0) grade 1

• Platelets greater than or equal to 100,000/mcl

• Creatinine less than or equal to 1.5 times institutional upper limit normal (ULN), CTCAE v3.0 grade 1

• Bilirubin less than or equal to 1.5 x ULN (CTCAE v3.0 grade 1)

• Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) less than or equal to 2.5 x ULN (CTCAE v3.0 grade 1)

• Alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v3.0 grade 1)

• Urine protein creatinine (UPC) ratio must be < 1.0 gram (gm); if UPC ratio >= 1, collection of 24-hour urine measurement of urine protein is recommended (24-hour urine protein level must be < 1000 mg for patient enrollment)

• UPC ratio of spot urine is an estimation of the 24 urine protein excretion

• A UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm

• Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) =< 1.5 x ULN

• Fasting cholesterol less than 300 mg/dL (CTCAE v3.0 grade 1)

• Fasting triglycerides =< 2.5 x ULN (CTCAE v3.0 grade 1)

• Patients must NOT have received prior chemotherapy or targeted therapy, including chemotherapy used for radiation sensitization for treatment of endometrial carcinoma

• Patients must NOT have received prior therapy with bevacizumab or other VEGF pathway targeted therapy; patients must NOT have received prior therapy with temsirolimus, everolimus, ridaforolimus, sirolimus, or any other PI3K/ v-akt murine thymoma viral oncogene homolog 1 (AKT)/mammalian target of rapamycins (mTor) pathway targeted therapy

• Patients may have receive prior radiation therapy for treatment of endometrial carcinoma; prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy; all radiation therapy must be completed at least 4 weeks prior to the first date of study therapy; the prior radiation field, radiation dose, number of fractions and prior radiation start and stop dates must be provided on the Fast Fact Sheet (FFS) at registration

• Patients may have received prior hormonal therapy for treatment of endometrial carcinoma; all hormonal therapy must be discontinued at least one week prior to the first date of study therapy

• Patients must have signed an approved informed consent and authorization permitting release of personal health information

Exclusion Criteria:

• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, and other specific malignancies as noted below, are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy

• Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease

• Patients who have received prior chemotherapy for any abdominal or pelvic tumor within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease

• Patients with serious, non-healing wound, ulcer, or bone fracture; this includes history of abdominal/pelvic fistula, gastrointestinal perforation or intra-abdominal abscess within 3 months prior to the first date of study therapy; patients with underlying lesions that caused the fistula or perforation in the past that have not been corrected

• Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels

• Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy or any brain metastases

• Patients with clinically significant cardiovascular disease; this includes:

• Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm Hg

• Myocardial infarction or unstable angina within 6 months of the first date of study therapy

• New York Heart Association (NYHA) class II or greater congestive heart failure

• History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)

• CTCAE grade 2 or greater peripheral vascular disease.

• History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of study therapy.

• Aortic aneurysm and/or history of aortic dissection

• Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies

• Patients undergoing invasive procedures as defined below:

• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of bevacizumab or temsirolimus therapy

• Major surgical procedure anticipated during the course of the study.

• Minor surgical procedures, fine needle aspirates, or core biopsies within 7 days prior to the first date of study therapy

• Patients with known prior history of interstitial pneumonitis

• Patients with CTCAE v. 3, grade 2 or greater hypoxemia

• Patients with CTCAE v. 3, grade 2 or greater dyspnea

• Patients must not have uncontrolled diabetes, and must not have baseline hemoglobin A1C (HgbA1C) > 8

• Patients with peripheral neuropathy > CTCAE v.3, grade 1

• Patients who are pregnant or nursing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Saint Joseph's Hospital and Medical Center	Phoenix	Arizona	United States	85013
2	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
3	University of Arizona Cancer Center-North Campus	Tucson	Arizona	United States	85719
4	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
5	John Muir Medical Center-Concord Campus	Concord	California	United States	94520
6	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
7	UCLA / Jonsson Comprehensive Cancer Center	Los Angeles	California	United States	90095
8	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California	United States	94040
9	UC San Diego Medical Center - Hillcrest	San Diego	California	United States	92103
10	San Diego VA Medical Center	San Diego	California	United States	92161
11	UCSF Medical Center-Mount Zion	San Francisco	California	United States	94115
12	John Muir Medical Center-Walnut Creek	Walnut Creek	California	United States	94598
13	University of Colorado Hospital	Aurora	Colorado	United States	80045
14	Rocky Mountain Gynecologic Oncology PC	Englewood	Colorado	United States	80110
15	Hartford Hospital	Hartford	Connecticut	United States	06102
16	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut	United States	06105
17	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
18	Yale University	New Haven	Connecticut	United States	06520
19	Beebe Medical Center	Lewes	Delaware	United States	19958
20	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
21	MedStar Washington Hospital Center	Washington	District of Columbia	United States	20010
22	Morton Plant Hospital	Clearwater	Florida	United States	33756
23	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224-9980
24	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
25	AdventHealth Orlando	Orlando	Florida	United States	32803
26	Orlando Health Cancer Institute	Orlando	Florida	United States	32806
27	Central Georgia Gynecologic Oncology	Macon	Georgia	United States	31201
28	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
29	Pali Momi Medical Center	'Aiea	Hawaii	United States	96701
30	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii	United States	96813
31	Queen's Medical Center	Honolulu	Hawaii	United States	96813
32	Straub Clinic and Hospital	Honolulu	Hawaii	United States	96813
33	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
34	Queen's Cancer Center - Kuakini	Honolulu	Hawaii	United States	96817
35	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii	United States	96817
36	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
37	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii	United States	96766
38	Maui Memorial Medical Center	Wailuku	Hawaii	United States	96793
39	Pacific Cancer Institute of Maui	Wailuku	Hawaii	United States	96793
40	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
41	Northwestern University	Chicago	Illinois	United States	60611
42	Rush University Medical Center	Chicago	Illinois	United States	60612
43	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
44	Advocate Sherman Hospital	Elgin	Illinois	United States	60123
45	Hinsdale Hematology Oncology Associates Incorporated	Hinsdale	Illinois	United States	60521
46	Sudarshan K Sharma MD Limited-Gynecologic Oncology	Hinsdale	Illinois	United States	60521
47	Elkhart Clinic	Elkhart	Indiana	United States	46514-2098
48	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana	United States	46514
49	Elkhart General Hospital	Elkhart	Indiana	United States	46515
50	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana	United States	46260
51	Community Howard Regional Health	Kokomo	Indiana	United States	46904
52	IU Health La Porte Hospital	La Porte	Indiana	United States	46350
53	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana	United States	46545
54	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana	United States	46545
55	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana	United States	46563
56	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
57	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana	United States	46601
58	South Bend Clinic	South Bend	Indiana	United States	46617
59	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46628
60	Michiana Hematology Oncology PC-Westville	Westville	Indiana	United States	46391
61	McFarland Clinic PC - Ames	Ames	Iowa	United States	50010
62	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa	United States	50325
63	Mercy Cancer Center-West Lakes	Clive	Iowa	United States	50325
64	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
65	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa	United States	50309
66	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
67	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
68	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
69	Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
70	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
71	Methodist West Hospital	West Des Moines	Iowa	United States	50266-7700
72	Mercy Medical Center-West Lakes	West Des Moines	Iowa	United States	50266
73	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
74	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
75	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
76	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
77	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
78	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
79	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
80	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
81	Cancer Center of Kansas-Liberal	Liberal	Kansas	United States	67905
82	Cancer Center of Kansas - McPherson	McPherson	Kansas	United States	67460
83	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
84	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
85	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
86	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
87	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
88	Associates In Womens Health	Wichita	Kansas	United States	67208
89	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
90	Ascension Via Christi Hospitals Wichita	Wichita	Kansas	United States	67214
91	Cancer Center of Kansas - Wichita	Wichita	Kansas	United States	67214
92	Wichita NCI Community Oncology Research Program	Wichita	Kansas	United States	67214
93	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
94	Baptist Health Lexington	Lexington	Kentucky	United States	40503
95	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
96	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky	United States	40202
97	Maine Medical Center-Bramhall Campus	Portland	Maine	United States	04102
98	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
99	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
100	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland	United States	21237
101	Christiana Care - Union Hospital	Elkton	Maryland	United States	21921
102	Baystate Medical Center	Springfield	Massachusetts	United States	01199
103	UMass Memorial Medical Center - Memorial Division	Worcester	Massachusetts	United States	01605
104	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan	United States	48106
105	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
106	Beaumont Hospital - Dearborn	Dearborn	Michigan	United States	48124
107	Ascension Saint John Hospital	Detroit	Michigan	United States	48236
108	Hurley Medical Center	Flint	Michigan	United States	48503
109	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan	United States	48532
110	Allegiance Health	Jackson	Michigan	United States	49201
111	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
112	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
113	Borgess Medical Center	Kalamazoo	Michigan	United States	49048
114	Sparrow Hospital	Lansing	Michigan	United States	48912
115	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan	United States	48154
116	Lakeland Hospital Niles	Niles	Michigan	United States	49120
117	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
118	Lake Huron Medical Center	Port Huron	Michigan	United States	48060
119	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
120	Ascension Saint Mary's Hospital	Saginaw	Michigan	United States	48601
121	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan	United States	49085
122	Marie Yeager Cancer Center	Saint Joseph	Michigan	United States	49085
123	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
124	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905
125	Saint Dominic-Jackson Memorial Hospital	Jackson	Mississippi	United States	39216
126	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
127	Singing River Hospital	Pascagoula	Mississippi	United States	39581
128	University of Missouri - Ellis Fischel	Columbia	Missouri	United States	65212
129	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri	United States	65401
130	SSM Health Saint Louis University Hospital	Saint Louis	Missouri	United States	63104
131	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
132	Cancer Research for the Ozarks NCORP	Springfield	Missouri	United States	65804
133	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
134	CoxHealth South Hospital	Springfield	Missouri	United States	65807
135	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
136	Women's Cancer Center of Nevada	Las Vegas	Nevada	United States	89106
137	Center of Hope at Renown Medical Center	Reno	Nevada	United States	89502
138	Renown Regional Medical Center	Reno	Nevada	United States	89502
139	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
140	Morristown Medical Center	Morristown	New Jersey	United States	07960
141	Virtua Memorial	Mount Holly	New Jersey	United States	08060
142	Rutgers New Jersey Medical School	Newark	New Jersey	United States	07101
143	Saint Luke's Hospital-Warren Campus	Phillipsburg	New Jersey	United States	08865
144	Overlook Hospital	Summit	New Jersey	United States	07902
145	Virtua Voorhees	Voorhees	New Jersey	United States	08043
146	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
147	Southwest Gynecologic Oncology Associates Inc	Albuquerque	New Mexico	United States	87106
148	Women's Cancer Care Associates LLC	Albany	New York	United States	12208
149	Island Gynecologic Oncology	Brightwaters	New York	United States	11718
150	State University of New York Downstate Medical Center	Brooklyn	New York	United States	11203
151	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
152	New York Hospital Medical Center of Queens	Fresh Meadows	New York	United States	11365
153	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
154	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
155	Hope Women's Cancer Centers-Asheville	Asheville	North Carolina	United States	28816
156	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina	United States	27215
157	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
158	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
159	Duke University Medical Center	Durham	North Carolina	United States	27710
160	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
161	Summa Health System - Akron Campus	Akron	Ohio	United States	44304
162	Cleveland Clinic Akron General	Akron	Ohio	United States	44307
163	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio	United States	45219
164	Case Western Reserve University	Cleveland	Ohio	United States	44106
165	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
166	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
167	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
168	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
169	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
170	Miami Valley Hospital	Dayton	Ohio	United States	45409
171	Kettering Medical Center	Kettering	Ohio	United States	45429
172	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
173	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio	United States	44060
174	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
175	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma	United States	74146
176	Jefferson Abington Hospital	Abington	Pennsylvania	United States	19001
177	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
178	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
179	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
180	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
181	Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19107
182	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
183	Geisinger Medical Group	State College	Pennsylvania	United States	16801
184	Reading Hospital	West Reading	Pennsylvania	United States	19611
185	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
186	Women and Infants Hospital	Providence	Rhode Island	United States	02905
187	Medical University of South Carolina	Charleston	South Carolina	United States	29425
188	South Carolina Oncology Associates PA	Columbia	South Carolina	United States	29210
189	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota	United States	57104
190	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
191	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
192	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
193	Parkland Memorial Hospital	Dallas	Texas	United States	75235
194	Clements University Hospital	Dallas	Texas	United States	75390
195	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
196	University of Texas Medical Branch	Galveston	Texas	United States	77555-0565
197	Lyndon Baines Johnson General Hospital	Houston	Texas	United States	77026-1967
198	M D Anderson Cancer Center	Houston	Texas	United States	77030
199	Scott and White Memorial Hospital	Temple	Texas	United States	76508
200	University of Vermont Medical Center	Burlington	Vermont	United States	05401
201	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908
202	Virginia Oncology Associates-Hampton	Hampton	Virginia	United States	23666
203	Virginia Oncology Associates - Lake Wright	Norfolk	Virginia	United States	23502
204	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
205	Carilion Clinic Gynecological Oncology	Roanoke	Virginia	United States	24016
206	PeaceHealth Medical Group PC	Bellingham	Washington	United States	98226
207	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington	United States	98310
208	Harrison Medical Center	Bremerton	Washington	United States	98310
209	Providence Regional Cancer Partnership	Everett	Washington	United States	98201
210	Skagit Regional Health Cancer Care Center	Mount Vernon	Washington	United States	98274
211	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington	United States	98370
212	Pacific Gynecology Specialists	Seattle	Washington	United States	98104
213	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
214	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
215	Kaiser Permanente Washington	Seattle	Washington	United States	98112
216	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
217	University of Washington Medical Center - Northwest	Seattle	Washington	United States	98133
218	University of Washington Medical Center - Montlake	Seattle	Washington	United States	98195
219	Olympic Medical Cancer Care Center	Sequim	Washington	United States	98384
220	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
221	MultiCare Deaconess Cancer and Blood Specialty Center - Downtown	Spokane	Washington	United States	99204
222	MultiCare Tacoma General Hospital	Tacoma	Washington	United States	98405
223	Saint Joseph Medical Center	Tacoma	Washington	United States	98405
224	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington	United States	99362
225	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801
226	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
227	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin	United States	53792
228	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
229	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
230	Aurora Sinai Medical Center	Milwaukee	Wisconsin	United States	53233
231	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin	United States	54904
232	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin	United States	53081
233	Aurora West Allis Medical Center	West Allis	Wisconsin	United States	53227

Sponsors and Collaborators

• National Cancer Institute (NCI)
• NRG Oncology

Investigators

• Principal Investigator: Carol Aghajanian, NRG Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00977574
• Other Study ID Numbers: NCI-2011-01969; NCI-2011-01969; GOG-0086P; CDR0000654472; GOG-0086P; GOG-0086P; U10CA180868; U10CA027469
• First Posted: Sep 15, 2009
• Last Update Posted: Jul 28, 2022
• Last Verified: Jun 1, 2022

• Additional relevant MeSH terms: Adenocarcinoma; Endometrial Neoplasms; Cystadenocarcinoma, Serous; Adenocarcinoma, Clear Cell; Carcinoma, Adenosquamous; Recurrence; Sirolimus; Paclitaxel; Epothilones; Epothilone B; Bevacizumab; Carboplatin; Albumin-Bound Paclitaxel; Antineoplastic Agents, Immunological; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G

Study Results

Participant Flow

Recruitment Details	Accrual of 349 patients from 48 main members and CCOP sites began on 9/14/2009 and completed on 01/09/2012 in 28 months; 5 months longer than expected. There were 11 patients deemed ineligible by central review most for reasons related to pathologic diagnosis. Ten patients refused all protocol treatment.

Arm/Group Title	Arm I (Paclitaxel, Carboplatin, Bevacizumab)	Arm II (Paclitaxel, Carboplatin, Temsirolimus)	Arm III (Ixabepilone, Carboplatin, Bevacizumab)
Arm/Group Description	Paclitaxel 175 mg/m2 IV over 3 hours day 1 Carboplatin AUC = 6 IV day 1 Bevacizumab 15mg/kg IV day 1 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Bevacizumab 15mg/kg IV every 21 days	Paclitaxel 175 mg/m2 IV over 3 hours day 1 Carboplatin AUC = 5 IV day 1 Temsirolimus 25 mg IV days 1 and 8 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Temsirolimus 25 mg IV weekly days 1, 8 and 15 (one cycle = 21 days)	Ixabepilone 30 mg/m2 IV over 1 hour day 1 Carboplatin AUC = 6 IV day 1 Bevacizumab 15mg/kg IV day 1 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Bevacizumab 15mg/kg IV every 21 days
Period Title: Overall Study
STARTED	116	115	118
COMPLETED	112	113	114
NOT COMPLETED	4	2	4

Baseline Characteristics

Arm/Group Title	Arm I (Paclitaxel, Carboplatin, Bevacizumab)	Arm II (Paclitaxel, Carboplatin, Temsirolimus)	Arm III (Ixabepilone, Carboplatin, Bevacizumab)	Total
Arm/Group Description	Paclitaxel 175 mg/m2 IV over 3 hours day 1 Carboplatin AUC = 6 IV day 1 Bevacizumab 15mg/kg IV day 1 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Bevacizumab 15mg/kg IV every 21 days	Paclitaxel 175 mg/m2 IV over 3 hours day 1 Carboplatin AUC = 5 IV day 1 Temsirolimus 25 mg IV days 1 and 8 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Temsirolimus 25 mg IV weekly days 1, 8 and 15 (one cycle = 21 days)	Ixabepilone 30 mg/m2 IV over 1 hour day 1 Carboplatin AUC = 6 IV day 1 Bevacizumab 15mg/kg IV day 1 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Bevacizumab 15mg/kg IV every 21 days	Total of all reporting groups
Overall Participants	116	115	118	349
Age, Customized (Count of Participants)
30-39 years	2 1.7%	2 1.7%	3 2.5%	7 2%
40-49 years	6 5.2%	5 4.3%	8 6.8%	19 5.4%
50-59 years	36 31%	35 30.4%	19 16.1%	90 25.8%
60-69 years	48 41.4%	50 43.5%	57 48.3%	155 44.4%
70-79 years	22 19%	22 19.1%	28 23.7%	72 20.6%
>=80 years	2 1.7%	1 0.9%	3 2.5%	6 1.7%
Sex: Female, Male (Count of Participants)
Female	116 100%	115 100%	118 100%	349 100%
Male	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Progressed or Died by 25 Months From Enrollment
Description	PFS (Progression free survival) is defined as the duration of time from date of study entry to time of progression or death, whichever occurs first. Patients with a status of alive, progression-free are censored at their date of last follow-up. To lessen the potential for bias in the progression evaluation times between treatment arms and historical controls, progression/death times will be grouped over 6 18-week time intervals. Progressions are carried forward to the end of the interval. All progressions or deaths occurring after the 6th 18-week interval are censored at 25 months for this analysis. Study NCT00977574
Time Frame	at 25 months

Outcome Measure Data

Analysis Population Description

All enrolled patients

Arm/Group Title	Arm I (Paclitaxel, Carboplatin, Bevacizumab)	Arm II (Paclitaxel, Carboplatin, Temsirolimus)	Arm III (Ixabepilone, Carboplatin, Bevacizumab)
Arm/Group Description	Paclitaxel 175 mg/m2 IV over 3 hours day 1 Carboplatin AUC = 6 IV day 1 Bevacizumab 15mg/kg IV day 1 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Bevacizumab 15mg/kg IV every 21 days	Paclitaxel 175 mg/m2 IV over 3 hours day 1 Carboplatin AUC = 5 IV day 1 Temsirolimus 25 mg IV days 1 and 8 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Temsirolimus 25 mg IV weekly days 1, 8 and 15 (one cycle = 21 days)	Ixabepilone 30 mg/m2 IV over 1 hour day 1 Carboplatin AUC = 6 IV day 1 Bevacizumab 15mg/kg IV day 1 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Bevacizumab 15mg/kg IV every 21 days
Measure Participants	116	115	118
Count of Participants [Participants]	86 74.1%	96 83.5%	88 74.6%

2. Secondary Outcome

Title	Frequency and Severity of Toxicity as Assessed by CTCAE v3.0 for Each of the Three Arms.
Time Frame	Median of 10 cycles of treatment plus 30 days

Outcome Measure Data

Analysis Population Description

Treated patients

Arm/Group Title	Arm I (Paclitaxel, Carboplatin, Bevacizumab)	Arm II (Paclitaxel, Carboplatin, Temsirolimus)	Arm III (Ixabepilone, Carboplatin, Bevacizumab)
Arm/Group Description	Paclitaxel 175 mg/m2 IV over 3 hours day 1 Carboplatin AUC = 6 IV day 1 Bevacizumab 15mg/kg IV day 1 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Bevacizumab 15mg/kg IV every 21 days	Paclitaxel 175 mg/m2 IV over 3 hours day 1 Carboplatin AUC = 5 IV day 1 Temsirolimus 25 mg IV days 1 and 8 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Temsirolimus 25 mg IV weekly days 1, 8 and 15 (one cycle = 21 days)	Ixabepilone 30 mg/m2 IV over 1 hour day 1 Carboplatin AUC = 6 IV day 1 Bevacizumab 15mg/kg IV day 1 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Bevacizumab 15mg/kg IV every 21 days
Measure Participants	112	113	114
Any Adverse Event, Any Grade	112 96.6%	113 98.3%	114 96.6%
Any Adverse Event, Grades >= 3	105 90.5%	111 96.5%	109 92.4%
Any Adverse Event, Grade 5	4 3.4%	6 5.2%	6 5.1%

3. Secondary Outcome

Title	The Median Duration of Overall Survival for Each of the Three Arms.
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	Time from date of study entry to time of death or the date of last contact, assessed up to 5 years

Outcome Measure Data

Analysis Population Description

All enrolled patients

Arm/Group Title	Arm I (Paclitaxel, Carboplatin, Bevacizumab)	Arm II (Paclitaxel, Carboplatin, Temsirolimus)	Arm III (Ixabepilone, Carboplatin, Bevacizumab)
Arm/Group Description	Paclitaxel 175 mg/m2 IV over 3 hours day 1 Carboplatin AUC = 6 IV day 1 Bevacizumab 15mg/kg IV day 1 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Bevacizumab 15mg/kg IV every 21 days	Paclitaxel 175 mg/m2 IV over 3 hours day 1 Carboplatin AUC = 5 IV day 1 Temsirolimus 25 mg IV days 1 and 8 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Temsirolimus 25 mg IV weekly days 1, 8 and 15 (one cycle = 21 days)	Ixabepilone 30 mg/m2 IV over 1 hour day 1 Carboplatin AUC = 6 IV day 1 Bevacizumab 15mg/kg IV day 1 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Bevacizumab 15mg/kg IV every 21 days
Measure Participants	116	115	118
Median (95% Confidence Interval) [months]	34	25	25.2

4. Secondary Outcome

Title	The Proportion of Patients With Measurable Disease Who Have Confirmed Objective Tumor Responses by Treatment.
Description	RECIST 1.1 was used to define objective tumor response. A complete response is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. A partial response is defined as At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. There can be no unequivocal progression of non-target lesions and no new lesions. Complete and partial responses are included in the objective tumor response rate. Confirmation of response was not required.
Time Frame	Imaging was done every 3 cycles and at any other time clinically indicated. Imaging was required every 9 weeks until progression or initiation on non protocol therapy. After 2 years of protocol therapy or follow up, CT scan or MRI was every 3 months

Outcome Measure Data

Analysis Population Description

Enrolled patients with measurable disease

Arm/Group Title	Arm I (Paclitaxel, Carboplatin, Bevacizumab)	Arm II (Paclitaxel, Carboplatin, Temsirolimus)	Arm III (Ixabepilone, Carboplatin, Bevacizumab)
Arm/Group Description	Paclitaxel 175 mg/m2 IV over 3 hours day 1 Carboplatin AUC = 6 IV day 1 Bevacizumab 15mg/kg IV day 1 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Bevacizumab 15mg/kg IV every 21 days	Paclitaxel 175 mg/m2 IV over 3 hours day 1 Carboplatin AUC = 5 IV day 1 Temsirolimus 25 mg IV days 1 and 8 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Temsirolimus 25 mg IV weekly days 1, 8 and 15 (one cycle = 21 days)	Ixabepilone 30 mg/m2 IV over 1 hour day 1 Carboplatin AUC = 6 IV day 1 Bevacizumab 15mg/kg IV day 1 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Bevacizumab 15mg/kg IV every 21 days
Measure Participants	89	85	85
Count of Participants [Participants]	53 45.7%	47 40.9%	45 38.1%

Adverse Events

Time Frame	Assessed every cycle while on treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up
Arm/Group Title	Arm I (Paclitaxel, Carboplatin, Bevacizumab)		Arm II (Paclitaxel, Carboplatin, Temsirolimus)		Arm III (Ixabepilone, Carboplatin, Bevacizumab)
Arm/Group Description	Paclitaxel 175 mg/m2 IV over 3 hours day 1 Carboplatin AUC = 6 IV day 1 Bevacizumab 15mg/kg IV day 1 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Bevacizumab 15mg/kg IV every 21 days		Paclitaxel 175 mg/m2 IV over 3 hours day 1 Carboplatin AUC = 5 IV day 1 Temsirolimus 25 mg IV days 1 and 8 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Temsirolimus 25 mg IV weekly days 1, 8 and 15 (one cycle = 21 days)		Ixabepilone 30 mg/m2 IV over 1 hour day 1 Carboplatin AUC = 6 IV day 1 Bevacizumab 15mg/kg IV day 1 (starting with cycle 2 for those patients who are entering post surgery) Maintenance regimen - Bevacizumab 15mg/kg IV every 21 days
All Cause Mortality
	Arm I (Paclitaxel, Carboplatin, Bevacizumab)		Arm II (Paclitaxel, Carboplatin, Temsirolimus)		Arm III (Ixabepilone, Carboplatin, Bevacizumab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (Paclitaxel, Carboplatin, Bevacizumab)		Arm II (Paclitaxel, Carboplatin, Temsirolimus)		Arm III (Ixabepilone, Carboplatin, Bevacizumab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/112 (42.9%)		57/113 (50.4%)		53/114 (46.5%)
Blood and lymphatic system disorders
Neutrophils	2/112 (1.8%)		4/113 (3.5%)		1/114 (0.9%)
Platelets	3/112 (2.7%)		1/113 (0.9%)		4/114 (3.5%)
Leukocytes	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Hemoglobin	4/112 (3.6%)		1/113 (0.9%)		1/114 (0.9%)
Edema: Limb	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Cardiac disorders
S/N Arrhythmia: Atrial Fibrillation	0/112 (0%)		1/113 (0.9%)		1/114 (0.9%)
Vasovagal Episode	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Supraventricular Tachycardia	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Cardiac Ischemia/Infarction	1/112 (0.9%)		0/113 (0%)		1/114 (0.9%)
Hypertension	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Left Venticular Diastolic Dysfunction	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Lt Ventricular Systolic Dysfunction	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Gastrointestinal disorders
Fistula, Gi - Colon/Cecum/Appendix	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Perforation, Gi - Colon	1/112 (0.9%)		1/113 (0.9%)		0/114 (0%)
Fistula, Gi - Rectum	1/112 (0.9%)		0/113 (0%)		1/114 (0.9%)
Obstruction, Gi - Colon	2/112 (1.8%)		0/113 (0%)		1/114 (0.9%)
Ileus	1/112 (0.9%)		0/113 (0%)		1/114 (0.9%)
Dysphagia	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Leak, Gi - Small Bowel	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Obstruction, Gi - Small Bowel Nos	1/112 (0.9%)		1/113 (0.9%)		2/114 (1.8%)
Colitis	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Perforation, Gi - Small Bowel Nos	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Vomiting	1/112 (0.9%)		2/113 (1.8%)		3/114 (2.6%)
Dehydration	2/112 (1.8%)		1/113 (0.9%)		5/114 (4.4%)
Constipation	0/112 (0%)		1/113 (0.9%)		1/114 (0.9%)
Nausea	1/112 (0.9%)		1/113 (0.9%)		0/114 (0%)
Gastrointestinal - Other	0/112 (0%)		1/113 (0.9%)		1/114 (0.9%)
Diarrhea	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
General disorders
Fever	0/112 (0%)		1/113 (0.9%)		1/114 (0.9%)
Weight Loss	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Fatigue	0/112 (0%)		0/113 (0%)		2/114 (1.8%)
Death No Ctcae Term - Disease Progression Nos	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Death No Ctcae Term - Death Nos	2/112 (1.8%)		1/113 (0.9%)		4/114 (3.5%)
Death No Ctcae Term - Multi-Organ Failure	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Pain: Chest /Thorax Nos	0/112 (0%)		2/113 (1.8%)		0/114 (0%)
Pain: Head/Headache	1/112 (0.9%)		0/113 (0%)		2/114 (1.8%)
Pain: Back	0/112 (0%)		2/113 (1.8%)		0/114 (0%)
Pain: Joint	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Pain: Gallbladder	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Pain: Abdominal Pain Nos	2/112 (1.8%)		1/113 (0.9%)		3/114 (2.6%)
Pain: Muscle	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Hepatobiliary disorders
Cholecystitis	1/112 (0.9%)		1/113 (0.9%)		0/114 (0%)
Immune system disorders
Allergic Reaction/Hypersensitivity	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Infections and infestations
Inf W/Gr 3 Or 4 Anc: Blood	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Lung(Pneumonia)	2/112 (1.8%)		1/113 (0.9%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Soft Tissue Nos	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Bone	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Blood	0/112 (0%)		2/113 (1.8%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Wound	1/112 (0.9%)		0/113 (0%)		1/114 (0.9%)
Inf W/Nml Or Gr 1 Or 2 Anc: Oral Cavity-Gums	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Skin(Cellulitis)	1/112 (0.9%)		2/113 (1.8%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Catheter-Related	2/112 (1.8%)		2/113 (1.8%)		0/114 (0%)
Febrile Neutropenia	2/112 (1.8%)		2/113 (1.8%)		2/114 (1.8%)
Inf Unknown Anc: Lung (Pneumonia)	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Inf W/Nml Or Gr 1 Or 2 Anc: Urinary Tract Nos	0/112 (0%)		2/113 (1.8%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Abdomen Nos	0/112 (0%)		0/113 (0%)		2/114 (1.8%)
Inf Unknown Anc: Blood	2/112 (1.8%)		0/113 (0%)		0/114 (0%)
Inf W/Gr 3 Or 4 Anc: Bladder (Urinary)	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Colitis, Infectious (Eg.C. Difficile)	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Inf W/Nml Or Gr 1 Or 2 Anc: Nerve-Peripheral	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Pharynx	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Pelvis Nos	1/112 (0.9%)		0/113 (0%)		1/114 (0.9%)
Inf Unknown Anc: Wound	0/112 (0%)		2/113 (1.8%)		0/114 (0%)
Inf Unknown Anc: Foreign Body	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Foreign Body	0/112 (0%)		2/113 (1.8%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Bladder	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Inf W/Gr 3 Or 4 Anc: Catheter-Related	1/112 (0.9%)		1/113 (0.9%)		0/114 (0%)
Metabolism and nutrition disorders
Metabolic/Laboratory - Other	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Proteinuria	2/112 (1.8%)		0/113 (0%)		2/114 (1.8%)
Creatinine	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Alkaline Phosphatase	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Bilirubin	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Hypophosphatemia	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Hyperuricemia	1/112 (0.9%)		1/113 (0.9%)		0/114 (0%)
Hypertriglyceridemia	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Hypokalemia	0/112 (0%)		1/113 (0.9%)		1/114 (0.9%)
Hypoglycemia	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Musculoskeletal and connective tissue disorders
Soft Tissue Necrosis - Abdomen	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Joint Effusion	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Fracture	2/112 (1.8%)		0/113 (0%)		0/114 (0%)
Nervous system disorders
Syncope	3/112 (2.7%)		0/113 (0%)		0/114 (0%)
Neurology - Other	1/112 (0.9%)		0/113 (0%)		1/114 (0.9%)
Seizure	1/112 (0.9%)		0/113 (0%)		1/114 (0.9%)
Cns Ischemia	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Confusion	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Dizziness	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Neuropathy-Motor	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Renal and urinary disorders
Urinary Retention	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Obstruction, Gu - Ureter	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	0/112 (0%)		2/113 (1.8%)		1/114 (0.9%)
Pneumonitis	0/112 (0%)		2/113 (1.8%)		0/114 (0%)
Pleural Effusion	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Dyspnea	0/112 (0%)		4/113 (3.5%)		2/114 (1.8%)
Skin and subcutaneous tissue disorders
Injection Site Reaction	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Wound Complication, Non-Infectious	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Rash	0/112 (0%)		1/113 (0.9%)		1/114 (0.9%)
Vascular disorders
Inr	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Hemorrhage, Gu - Urinary Nos	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Hemorrhage, Gi - Rectum	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Hemorrhage/Pulmonary - Nose	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Hematoma	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Hemorrhage/Pulmonary - Bronchus	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Thrombosis/Embolism (Vascular Access-Related)	1/112 (0.9%)		1/113 (0.9%)		0/114 (0%)
Thrombosis/Thrombus/Embolism	4/112 (3.6%)		4/113 (3.5%)		3/114 (2.6%)
Other (Not Including Serious) Adverse Events
	Arm I (Paclitaxel, Carboplatin, Bevacizumab)		Arm II (Paclitaxel, Carboplatin, Temsirolimus)		Arm III (Ixabepilone, Carboplatin, Bevacizumab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	112/112 (100%)		113/113 (100%)		113/114 (99.1%)
Blood and lymphatic system disorders
Neutrophils	106/112 (94.6%)		106/113 (93.8%)		102/114 (89.5%)
Platelets	87/112 (77.7%)		96/113 (85%)		101/114 (88.6%)
Blood/Bone Marrow - Other	1/112 (0.9%)		0/113 (0%)		2/114 (1.8%)
Leukocytes	110/112 (98.2%)		110/113 (97.3%)		105/114 (92.1%)
Lymphopenia	9/112 (8%)		8/113 (7.1%)		6/114 (5.3%)
Hemoglobin	105/112 (93.8%)		111/113 (98.2%)		110/114 (96.5%)
Lymphatics - Other	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Edema: Viscera	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Edema: Trunk/Genital	0/112 (0%)		3/113 (2.7%)		0/114 (0%)
Edema: Limb	25/112 (22.3%)		46/113 (40.7%)		28/114 (24.6%)
Edema: Head And Neck	1/112 (0.9%)		6/113 (5.3%)		3/114 (2.6%)
Cardiac disorders
S/N Arrhythmia: Atrial Fibrillation	1/112 (0.9%)		4/113 (3.5%)		0/114 (0%)
Palpitations	5/112 (4.5%)		5/113 (4.4%)		4/114 (3.5%)
Cardiac Arrhythmia - Other	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
S/N Arrhythmia: Sinus Tachycardia	5/112 (4.5%)		1/113 (0.9%)		3/114 (2.6%)
Vasovagal Episode	1/112 (0.9%)		0/113 (0%)		1/114 (0.9%)
Supraventricular Tachycardia	1/112 (0.9%)		0/113 (0%)		1/114 (0.9%)
S/N Arrhythmia: Sinus Bradycardia	2/112 (1.8%)		0/113 (0%)		2/114 (1.8%)
Ventricular Arrhythmia - Arrhythmia Nos	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Ventricular Arrhythmia - Pvcs	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Cardiac Ischemia/Infarction	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Hypertension	51/112 (45.5%)		18/113 (15.9%)		50/114 (43.9%)
Valvular Heart Disease	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Left Venticular Diastolic Dysfunction	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Lt Ventricular Systolic Dysfunction	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Hypotension	6/112 (5.4%)		3/113 (2.7%)		5/114 (4.4%)
Cardipulmonary Arrest	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Ear and labyrinth disorders
Otitis Middle Ear	2/112 (1.8%)		0/113 (0%)		0/114 (0%)
Auditory/Ear - Other	3/112 (2.7%)		3/113 (2.7%)		3/114 (2.6%)
Hearing (Without Monitoring Program)	6/112 (5.4%)		3/113 (2.7%)		6/114 (5.3%)
Tinnitus	13/112 (11.6%)		6/113 (5.3%)		12/114 (10.5%)
Hearing (Monitoring Program)	0/112 (0%)		0/113 (0%)		3/114 (2.6%)
Endocrine disorders
Hot Flashes	12/112 (10.7%)		9/113 (8%)		5/114 (4.4%)
Endocrine - Other	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Hypothyroidism	0/112 (0%)		0/113 (0%)		2/114 (1.8%)
Eye disorders
Ocular/Visual - Other	7/112 (6.3%)		1/113 (0.9%)		1/114 (0.9%)
Uveitis	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Proptosis/Enophthalmos	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Watery Eye	0/112 (0%)		4/113 (3.5%)		2/114 (1.8%)
Glaucoma	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Dry Eye	1/112 (0.9%)		3/113 (2.7%)		3/114 (2.6%)
Ocular Surface Disease	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Cataract	2/112 (1.8%)		1/113 (0.9%)		0/114 (0%)
Photophobia	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Flashing Lights/Floaters	4/112 (3.6%)		2/113 (1.8%)		6/114 (5.3%)
Diplopia	0/112 (0%)		0/113 (0%)		2/114 (1.8%)
Blurred Vision	19/112 (17%)		10/113 (8.8%)		20/114 (17.5%)
Eyelid Dysfunction	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Gastrointestinal disorders
Proctitis	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Salivary Gland Changes	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Flatulence	4/112 (3.6%)		2/113 (1.8%)		4/114 (3.5%)
Fistula, Gi - Rectum	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Obstruction, Gi - Colon	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Gastritis	2/112 (1.8%)		0/113 (0%)		1/114 (0.9%)
Esophagitis	2/112 (1.8%)		0/113 (0%)		2/114 (1.8%)
Hemorrhoids	5/112 (4.5%)		2/113 (1.8%)		3/114 (2.6%)
Heartburn	12/112 (10.7%)		7/113 (6.2%)		8/114 (7%)
Mucositis (Functional/Sympt) - Esophagus	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Dental: Teeth	2/112 (1.8%)		0/113 (0%)		0/114 (0%)
Leak, Gi - Leak Nos	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Ascites	0/112 (0%)		4/113 (3.5%)		2/114 (1.8%)
Ileus	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Dysphagia	7/112 (6.3%)		6/113 (5.3%)		9/114 (7.9%)
Distention	5/112 (4.5%)		6/113 (5.3%)		8/114 (7%)
Taste Alteration	13/112 (11.6%)		25/113 (22.1%)		17/114 (14.9%)
Incontinence, Anal	0/112 (0%)		1/113 (0.9%)		1/114 (0.9%)
Dry Mouth	0/112 (0%)		5/113 (4.4%)		3/114 (2.6%)
Mucositis (Functional/Sympt) - Oral Cavity	14/112 (12.5%)		26/113 (23%)		14/114 (12.3%)
Obstruction, Gi - Small Bowel Nos	0/112 (0%)		3/113 (2.7%)		1/114 (0.9%)
Fistula, Gi - Oral Cavity	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Colitis	0/112 (0%)		2/113 (1.8%)		0/114 (0%)
Mucositis (Clinical Exam) - Stomach	1/112 (0.9%)		1/113 (0.9%)		0/114 (0%)
Mucositis (Clinical Exam) - Oral Cavity	15/112 (13.4%)		27/113 (23.9%)		7/114 (6.1%)
Vomiting	46/112 (41.1%)		36/113 (31.9%)		51/114 (44.7%)
Anorexia	53/112 (47.3%)		46/113 (40.7%)		50/114 (43.9%)
Dehydration	13/112 (11.6%)		10/113 (8.8%)		17/114 (14.9%)
Constipation	66/112 (58.9%)		58/113 (51.3%)		66/114 (57.9%)
Nausea	78/112 (69.6%)		73/113 (64.6%)		81/114 (71.1%)
Gastrointestinal - Other	4/112 (3.6%)		2/113 (1.8%)		3/114 (2.6%)
Diarrhea	55/112 (49.1%)		47/113 (41.6%)		55/114 (48.2%)
General disorders
Constitutional Symptoms - Other	5/112 (4.5%)		0/113 (0%)		4/114 (3.5%)
Sweating	4/112 (3.6%)		0/113 (0%)		3/114 (2.6%)
Weight Gain	16/112 (14.3%)		7/113 (6.2%)		8/114 (7%)
Patient Odor	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Fever	17/112 (15.2%)		14/113 (12.4%)		14/114 (12.3%)
Weight Loss	24/112 (21.4%)		29/113 (25.7%)		31/114 (27.2%)
Hypothermia	1/112 (0.9%)		0/113 (0%)		1/114 (0.9%)
Rigors/Chills	6/112 (5.4%)		4/113 (3.5%)		7/114 (6.1%)
Fatigue	100/112 (89.3%)		90/113 (79.6%)		98/114 (86%)
Insomnia	24/112 (21.4%)		31/113 (27.4%)		22/114 (19.3%)
Death No Ctcae Term - Disease Progression Nos	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Pain - Other	9/112 (8%)		6/113 (5.3%)		12/114 (10.5%)
Pain: Urethra	4/112 (3.6%)		3/113 (2.7%)		1/114 (0.9%)
Pain: Pelvis	6/112 (5.4%)		4/113 (3.5%)		2/114 (1.8%)
Pain: Breast	0/112 (0%)		1/113 (0.9%)		1/114 (0.9%)
Pain: Vagina	3/112 (2.7%)		2/113 (1.8%)		1/114 (0.9%)
Pain: Chest /Thorax Nos	9/112 (8%)		5/113 (4.4%)		14/114 (12.3%)
Pain: Chest Wall	7/112 (6.3%)		1/113 (0.9%)		3/114 (2.6%)
Pain: Throat/Pharynx/Larynx	8/112 (7.1%)		7/113 (6.2%)		4/114 (3.5%)
Pain: Pleura	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Pain: Eye	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Pain: Head/Headache	51/112 (45.5%)		21/113 (18.6%)		39/114 (34.2%)
Pain: Neck	6/112 (5.4%)		3/113 (2.7%)		4/114 (3.5%)
Pain: Extremity-Limb	39/112 (34.8%)		23/113 (20.4%)		29/114 (25.4%)
Pain: Buttock	0/112 (0%)		3/113 (2.7%)		0/114 (0%)
Pain: Back	27/112 (24.1%)		19/113 (16.8%)		20/114 (17.5%)
Pain: Joint	52/112 (46.4%)		30/113 (26.5%)		42/114 (36.8%)
Pain: Bone	8/112 (7.1%)		5/113 (4.4%)		12/114 (10.5%)
Pain: Kidney	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Pain: Bladder	3/112 (2.7%)		0/113 (0%)		4/114 (3.5%)
Pain: Pain Nos	7/112 (6.3%)		4/113 (3.5%)		6/114 (5.3%)
Pain: Stomach	3/112 (2.7%)		0/113 (0%)		0/114 (0%)
Pain: Rectum	3/112 (2.7%)		3/113 (2.7%)		2/114 (1.8%)
Pain: Oral Cavity	5/112 (4.5%)		8/113 (7.1%)		2/114 (1.8%)
Pain: Esophagus	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Pain: Dental/Teeth/Peridontal	3/112 (2.7%)		1/113 (0.9%)		2/114 (1.8%)
Pain: Abdominal Pain Nos	37/112 (33%)		40/113 (35.4%)		40/114 (35.1%)
Pain: Scalp	0/112 (0%)		1/113 (0.9%)		3/114 (2.6%)
Pain: Oral - Gums	3/112 (2.7%)		1/113 (0.9%)		2/114 (1.8%)
Pain: Skin	1/112 (0.9%)		1/113 (0.9%)		1/114 (0.9%)
Pain: Lip	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Pain: Middle Ear	2/112 (1.8%)		1/113 (0.9%)		1/114 (0.9%)
Pain: External Ear	2/112 (1.8%)		1/113 (0.9%)		1/114 (0.9%)
Pain: Cardiac/ Heart	3/112 (2.7%)		0/113 (0%)		1/114 (0.9%)
Pain: Tumor	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Pain: Muscle	30/112 (26.8%)		37/113 (32.7%)		25/114 (21.9%)
Pain: Anus	1/112 (0.9%)		0/113 (0%)		1/114 (0.9%)
Pain: Neuralgia	1/112 (0.9%)		2/113 (1.8%)		2/114 (1.8%)
Pain: Sinus	3/112 (2.7%)		0/113 (0%)		3/114 (2.6%)
Syndromes - Other	1/112 (0.9%)		0/113 (0%)		1/114 (0.9%)
Cytokine Release Syndrome	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Flu-Like Syndrome	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Hepatobiliary disorders
Cholecystitis	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Liver Dysfunction	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Immune system disorders
Allergic Reaction/Hypersensitivity	6/112 (5.4%)		5/113 (4.4%)		13/114 (11.4%)
Rhinitis	24/112 (21.4%)		15/113 (13.3%)		20/114 (17.5%)
Infections and infestations
Inf W/Gr 3 Or 4 Anc: Wound	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Inf W/Gr 3 Or 4 Anc: Blood	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Inf W/Gr 3 Or 4 Anc: Dental-Tooth	2/112 (1.8%)		0/113 (0%)		0/114 (0%)
Inf W/Gr 3 Or 4 Anc: Skin (Cellulitis)	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Vulva	0/112 (0%)		0/113 (0%)		4/114 (3.5%)
Inf W/Nml Or Gr 1 Or 2 Anc: Upper Airway Nos	5/112 (4.5%)		3/113 (2.7%)		9/114 (7.9%)
Inf W/Nml Or Gr 1 Or 2 Anc: Lung(Pneumonia)	2/112 (1.8%)		2/113 (1.8%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Eye Nos	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Inf W/Gr 3 Or 4 Anc: Peritoneal Cavity	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Blood	1/112 (0.9%)		1/113 (0.9%)		2/114 (1.8%)
Inf W/Nml Or Gr 1 Or 2 Anc: Wound	2/112 (1.8%)		0/113 (0%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Otitis Media Nos	2/112 (1.8%)		0/113 (0%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Skin(Cellulitis)	4/112 (3.6%)		5/113 (4.4%)		3/114 (2.6%)
Inf W/Nml Or Gr 1 Or 2 Anc: Heart	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Febrile Neutropenia	2/112 (1.8%)		2/113 (1.8%)		5/114 (4.4%)
Inf W/Nml Or Gr 1 Or 2 Anc: Lip/Perioral	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Inf Unknown Anc: Lung (Pneumonia)	1/112 (0.9%)		1/113 (0.9%)		0/114 (0%)
Inf Unknown Anc: Sinus	0/112 (0%)		0/113 (0%)		2/114 (1.8%)
Inf W/Nml Or Gr 1 Or 2 Anc: Dental-Tooth	3/112 (2.7%)		1/113 (0.9%)		2/114 (1.8%)
Inf W/Nml Or Gr 1 Or 2 Anc: Urinary Tract Nos	20/112 (17.9%)		11/113 (9.7%)		17/114 (14.9%)
Inf W/Nml Or Gr 1 Or 2 Anc: Abdomen Nos	0/112 (0%)		1/113 (0.9%)		1/114 (0.9%)
Inf Unknown Anc: Blood	0/112 (0%)		1/113 (0.9%)		1/114 (0.9%)
Infection - Other	8/112 (7.1%)		3/113 (2.7%)		2/114 (1.8%)
Inf W/Nml Or Gr 1 Or 2 Anc: Muscle	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Colitis, Infectious (Eg.C. Difficile)	0/112 (0%)		1/113 (0.9%)		3/114 (2.6%)
Inf W/Nml Or Gr 1 Or 2 Anc: Conjunctiva	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Inf Unknown Anc: Vulva	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Bronchus	0/112 (0%)		2/113 (1.8%)		2/114 (1.8%)
Inf W/Gr 3 Or 4 Anc: Abdomen Nos	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Inf Unknown Anc: Upper Airway Nos	1/112 (0.9%)		1/113 (0.9%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Pharynx	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Inf W/Nml Or Gr 1 Or 2 Anc: Vagina	2/112 (1.8%)		0/113 (0%)		2/114 (1.8%)
Inf W/Nml Or Gr 1 Or 2 Anc: Sinus	3/112 (2.7%)		2/113 (1.8%)		4/114 (3.5%)
Inf W/Nml Or Gr 1 Or 2 Anc: Pelvis Nos	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Inf Unknown Anc: Eye Nos	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Inf Unknown Anc: Lymphatic	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Inf Unknown Anc: Urinary Tract Nos	5/112 (4.5%)		2/113 (1.8%)		2/114 (1.8%)
Inf Unknown Anc: Catheter-Related	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Foreign Body	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Inf Unknown Anc: Skin (Cellulitis)	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Inf W/Gr 3 Or 4 Anc: Vagina	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Inf W/Gr 3 Or 4 Anc: Upper Airway Nos	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Inf W/Gr 3 Or 4 Anc: Sinus	2/112 (1.8%)		0/113 (0%)		1/114 (0.9%)
Inf W/Gr 3 Or 4 Anc: Nerve-Peripheral	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Inf W/Nml Or Gr 1 Or 2 Anc: Kidney	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Inf Unknown Anc: Ungual (Nails)	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Inf W/Nml Or Gr 1 Or 2 Anc: Bladder	2/112 (1.8%)		1/113 (0.9%)		3/114 (2.6%)
Inf W/Gr 3 Or 4 Anc: Urinary Tract Nos	4/112 (3.6%)		2/113 (1.8%)		6/114 (5.3%)
Inf W/Gr 3 Or 4 Anc: Catheter-Related	1/112 (0.9%)		1/113 (0.9%)		0/114 (0%)
Metabolism and nutrition disorders
Ast	20/112 (17.9%)		26/113 (23%)		20/114 (17.5%)
Gfr	1/112 (0.9%)		2/113 (1.8%)		3/114 (2.6%)
Metabolic/Laboratory - Other	5/112 (4.5%)		7/113 (6.2%)		8/114 (7%)
Alkalosis	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Cholesterol,serum High	7/112 (6.3%)		35/113 (31%)		2/114 (1.8%)
Proteinuria	16/112 (14.3%)		1/113 (0.9%)		15/114 (13.2%)
Creatinine	21/112 (18.8%)		21/113 (18.6%)		21/114 (18.4%)
Hypoalbuminemia	23/112 (20.5%)		31/113 (27.4%)		28/114 (24.6%)
Alt	21/112 (18.8%)		21/113 (18.6%)		16/114 (14%)
Alkaline Phosphatase	19/112 (17%)		25/113 (22.1%)		20/114 (17.5%)
Bilirubin	7/112 (6.3%)		7/113 (6.2%)		9/114 (7.9%)
Hypermagnesemia	7/112 (6.3%)		3/113 (2.7%)		8/114 (7%)
Hypophosphatemia	13/112 (11.6%)		20/113 (17.7%)		9/114 (7.9%)
Hyponatremia	27/112 (24.1%)		24/113 (21.2%)		34/114 (29.8%)
Hyperuricemia	1/112 (0.9%)		2/113 (1.8%)		0/114 (0%)
Hypertriglyceridemia	5/112 (4.5%)		31/113 (27.4%)		5/114 (4.4%)
Cpk	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Bicarbonate, Serum-Low	4/112 (3.6%)		4/113 (3.5%)		3/114 (2.6%)
Acidosis	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Hypernatremia	5/112 (4.5%)		4/113 (3.5%)		3/114 (2.6%)
Hypocalcemia	21/112 (18.8%)		28/113 (24.8%)		30/114 (26.3%)
Hyperkalemia	12/112 (10.7%)		8/113 (7.1%)		10/114 (8.8%)
Hyperglycemia	44/112 (39.3%)		48/113 (42.5%)		38/114 (33.3%)
Hypokalemia	27/112 (24.1%)		43/113 (38.1%)		30/114 (26.3%)
Hypoglycemia	5/112 (4.5%)		4/113 (3.5%)		3/114 (2.6%)
Hypercalcemia	7/112 (6.3%)		4/113 (3.5%)		3/114 (2.6%)
Hypomagnesemia	45/112 (40.2%)		36/113 (31.9%)		33/114 (28.9%)
Musculoskeletal and connective tissue disorders
Seroma	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Trismus	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Musculoskeletal/St: Other	7/112 (6.3%)		0/113 (0%)		4/114 (3.5%)
Joint-Function	4/112 (3.6%)		1/113 (0.9%)		3/114 (2.6%)
Fracture	3/112 (2.7%)		0/113 (0%)		2/114 (1.8%)
Extremity-Upper (Function)	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Gait/Walking	1/112 (0.9%)		0/113 (0%)		2/114 (1.8%)
Arthritis	9/112 (8%)		3/113 (2.7%)		8/114 (7%)
Muscle Weakness - Whole Body/Generalized	13/112 (11.6%)		11/113 (9.7%)		12/114 (10.5%)
Muscle Weakness - Trunk	0/112 (0%)		2/113 (1.8%)		0/114 (0%)
Muscle Weakness - Extremity-Upper	3/112 (2.7%)		0/113 (0%)		1/114 (0.9%)
Muscle Weakness - Extremity-Lower	4/112 (3.6%)		1/113 (0.9%)		4/114 (3.5%)
Nervous system disorders
Syncope	5/112 (4.5%)		3/113 (2.7%)		4/114 (3.5%)
Involuntary Movement	1/112 (0.9%)		1/113 (0.9%)		2/114 (1.8%)
Hydrocephalus	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Neurology - Other	3/112 (2.7%)		2/113 (1.8%)		1/114 (0.9%)
Mental Status	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Mood Alteration - Depression	19/112 (17%)		17/113 (15%)		19/114 (16.7%)
Mood Alteration - Anxiety	16/112 (14.3%)		17/113 (15%)		19/114 (16.7%)
Mood Alteration - Agitation	1/112 (0.9%)		1/113 (0.9%)		1/114 (0.9%)
Tremor	2/112 (1.8%)		1/113 (0.9%)		3/114 (2.6%)
Speech Impairment	2/112 (1.8%)		1/113 (0.9%)		2/114 (1.8%)
Seizure	1/112 (0.9%)		0/113 (0%)		1/114 (0.9%)
Somnolence	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Cognitive Disturbance	5/112 (4.5%)		0/113 (0%)		0/114 (0%)
Confusion	4/112 (3.6%)		1/113 (0.9%)		4/114 (3.5%)
Memory Impairment	6/112 (5.4%)		5/113 (4.4%)		4/114 (3.5%)
Dizziness	31/112 (27.7%)		12/113 (10.6%)		27/114 (23.7%)
Neuropathy,cranial - Cn Viii Hearing/Balance	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Neuropathy,cranial - Cn I Smell	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Neuropathy-Sensory	79/112 (70.5%)		77/113 (68.1%)		69/114 (60.5%)
Neuropathy-Motor	11/112 (9.8%)		4/113 (3.5%)		6/114 (5.3%)
Renal and urinary disorders
Renal/Genitourinary - Other	5/112 (4.5%)		2/113 (1.8%)		4/114 (3.5%)
Leak, Gu - Urethra	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Cystitis	2/112 (1.8%)		1/113 (0.9%)		2/114 (1.8%)
Urinary Retention	3/112 (2.7%)		5/113 (4.4%)		1/114 (0.9%)
Obstruction, Gu - Urethra	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Obstruction, Gu - Ureter	1/112 (0.9%)		0/113 (0%)		1/114 (0.9%)
Incontinence, Urinary	8/112 (7.1%)		8/113 (7.1%)		7/114 (6.1%)
Fistula, Gu - Vagina	2/112 (1.8%)		0/113 (0%)		2/114 (1.8%)
Renal Failure	1/112 (0.9%)		1/113 (0.9%)		0/114 (0%)
Urinary Frequency	21/112 (18.8%)		16/113 (14.2%)		14/114 (12.3%)
Reproductive system and breast disorders
Libido	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Irregular Menses	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Vaginal Dryness	0/112 (0%)		2/113 (1.8%)		0/114 (0%)
Sexual/Reproductive Function: Other	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Vaginitis	0/112 (0%)		3/113 (2.7%)		2/114 (1.8%)
Vaginal Stenosis	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Vaginal Mucositis	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Vaginal Discharge	6/112 (5.4%)		5/113 (4.4%)		4/114 (3.5%)
Respiratory, thoracic and mediastinal disorders
Pulmonary: Other	2/112 (1.8%)		3/113 (2.7%)		7/114 (6.1%)
Nasal/Paranasal Reactions	14/112 (12.5%)		5/113 (4.4%)		12/114 (10.5%)
Edema, Larynx	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Bronchospasm	1/112 (0.9%)		3/113 (2.7%)		3/114 (2.6%)
Atelectasis	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Aspiration	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Voice Changes	9/112 (8%)		1/113 (0.9%)		7/114 (6.1%)
Hypoxia	1/112 (0.9%)		3/113 (2.7%)		1/114 (0.9%)
Hiccoughs	0/112 (0%)		0/113 (0%)		2/114 (1.8%)
Cough	48/112 (42.9%)		37/113 (32.7%)		29/114 (25.4%)
Dlco	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Pneumonitis	0/112 (0%)		5/113 (4.4%)		1/114 (0.9%)
Pleural Effusion	0/112 (0%)		1/113 (0.9%)		2/114 (1.8%)
Dyspnea	49/112 (43.8%)		39/113 (34.5%)		56/114 (49.1%)
Skin and subcutaneous tissue disorders
Nail Changes	10/112 (8.9%)		17/113 (15%)		8/114 (7%)
Injection Site Reaction	0/112 (0%)		2/113 (1.8%)		0/114 (0%)
Hair Loss/Alopecia (Scalp Or Body)	88/112 (78.6%)		81/113 (71.7%)		83/114 (72.8%)
Erythema Multiforme	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Hypopigmentation	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Cheilitis	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Wound Complication, Non-Infectious	2/112 (1.8%)		2/113 (1.8%)		1/114 (0.9%)
Bruising	10/112 (8.9%)		9/113 (8%)		9/114 (7.9%)
Acne	2/112 (1.8%)		10/113 (8.8%)		1/114 (0.9%)
Rash	18/112 (16.1%)		52/113 (46%)		19/114 (16.7%)
Dry Skin	4/112 (3.6%)		10/113 (8.8%)		3/114 (2.6%)
Decubitus	2/112 (1.8%)		0/113 (0%)		0/114 (0%)
Atrophy, Skin	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Pruritus	12/112 (10.7%)		18/113 (15.9%)		12/114 (10.5%)
Urticaria	1/112 (0.9%)		1/113 (0.9%)		0/114 (0%)
Flushing	5/112 (4.5%)		11/113 (9.7%)		6/114 (5.3%)
Hand-Foot	1/112 (0.9%)		1/113 (0.9%)		0/114 (0%)
Dermatology/Skin - Other	5/112 (4.5%)		8/113 (7.1%)		3/114 (2.6%)
Hyperpigmentation	2/112 (1.8%)		1/113 (0.9%)		2/114 (1.8%)
Ulceration	2/112 (1.8%)		4/113 (3.5%)		3/114 (2.6%)
Vascular disorders
Inr	4/112 (3.6%)		9/113 (8%)		8/114 (7%)
Coagulopathy - Other	1/112 (0.9%)		1/113 (0.9%)		1/114 (0.9%)
Ptt	4/112 (3.6%)		4/113 (3.5%)		5/114 (4.4%)
Hemorrhage, Gu - Urinary Nos	3/112 (2.7%)		1/113 (0.9%)		3/114 (2.6%)
Hemorrhage, Gu - Vagina	11/112 (9.8%)		8/113 (7.1%)		14/114 (12.3%)
Hemorrhage/Pulmonary - Bronchopulmonary Nos	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Hemorrhage, Gi - Rectum	5/112 (4.5%)		1/113 (0.9%)		8/114 (7%)
Hemorrhage/Pulmonary - Respiratory Tract Nos	1/112 (0.9%)		0/113 (0%)		1/114 (0.9%)
Hemorrhage, Gi - Varices (Rectal)	2/112 (1.8%)		0/113 (0%)		1/114 (0.9%)
Hemorrhage/Pulmonary - Nose	34/112 (30.4%)		24/113 (21.2%)		32/114 (28.1%)
Hematoma	4/112 (3.6%)		0/113 (0%)		2/114 (1.8%)
Hemorrhage, Gi - Anus	0/112 (0%)		1/113 (0.9%)		1/114 (0.9%)
Hemorrhage, Gu - Uterus	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Hemorrhage, Gu - Ureter	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Hemorrhage, Gi - Lower Gi Nos	1/112 (0.9%)		1/113 (0.9%)		0/114 (0%)
Hemorrhage, Gi - Oral Cavity	3/112 (2.7%)		0/113 (0%)		3/114 (2.6%)
Hemorrhage, Gu - Bladder	1/112 (0.9%)		0/113 (0%)		1/114 (0.9%)
Petechiae	1/112 (0.9%)		0/113 (0%)		1/114 (0.9%)
Hemorrhage/Bleeding - Other	0/112 (0%)		1/113 (0.9%)		0/114 (0%)
Vascular - Other	0/112 (0%)		0/113 (0%)		1/114 (0.9%)
Thrombosis/Embolism (Vascular Access-Related)	1/112 (0.9%)		0/113 (0%)		0/114 (0%)
Thrombosis/Thrombus/Embolism	5/112 (4.5%)		10/113 (8.8%)		10/114 (8.8%)
Phlebitis	0/112 (0%)		1/113 (0.9%)		0/114 (0%)

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.