Paclitaxel and Carboplatin With or Without Bevacizumab in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01167712
• Collaborator: NRG Oncology (Other)
• Enrollment: 692
• Locations: 573
• Arms: 2
• Anticipated Duration (Months): 152.3
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase III clinical trial studies two different dose schedules of paclitaxel to see how well they work in combination with carboplatin with or without bevacizumab in treating patients with stage II, III or IV ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bevacizumab is a type of drug called a monoclonal antibody and blocks tumor growth by stopping the growth of blood vessels that tumors need to grow. It is not yet known whether giving paclitaxel with combination chemotherapy once every three weeks is more effective than giving paclitaxel once a week in treating patients with ovarian, primary peritoneal, or fallopian tube cancer.

Condition or Disease	Intervention/Treatment	Phase
Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinofibroma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Ovarian Undifferentiated Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIA Fallopian Tube Cancer AJCC v6 and v7; Stage IIA Ovarian Cancer AJCC V6 and v7; Stage IIB Fallopian Tube Cancer AJCC v6 and v7; Stage IIB Ovarian Cancer AJCC v6 and v7; Stage IIC Fallopian Tube Cancer AJCC v6 and v7; Stage IIC Ovarian Cancer AJCC v6 and v7; Stage IIIA Fallopian Tube Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIA Primary Peritoneal Cancer AJCC v7; Stage IIIB Fallopian Tube Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIB Primary Peritoneal Cancer AJCC v7; Stage IIIC Fallopian Tube Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IIIC Primary Peritoneal Cancer AJCC v7; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7	Biological: Bevacizumab; Drug: Carboplatin; Procedure: Computed Tomography; Drug: Paclitaxel; Procedure: Therapeutic Conventional Surgery	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. To determine if the weekly paclitaxel regimen increases the time until first progression or death (progression-free survival [PFS]) compared to the every-3-week paclitaxel regimen in women with primary stage II, III or IV epithelial ovarian, peritoneal or fallopian tube cancer who are receiving carboplatin with or without bevacizumab.

SECONDARY OBJECTIVES:

1. To determine if the weekly paclitaxel increases the duration of overall survival compared to the every-3-week paclitaxel when combined with carboplatin with or without bevacizumab.

2. To compare the weekly paclitaxel to the every-3-week paclitaxel with respect to the incidence of severe or serious adverse events when it is combined with carboplatin with or without bevacizumab.

3. To compare the weekly paclitaxel to the every-3-week paclitaxel with respect to patients' self-reported quality of life (QOL) as measured by the Functional Assessment of Cancer Therapy-Ovarian (FACT-O)-Trial Outcome Index (TOI), when paclitaxel is combined with carboplatin with or without bevacizumab. (As of 02/08/2012, the QOL portion of this study is complete; patients enrolled after this date will not have QOL assessments)

TRANSLATIONAL RESEARCH OBJECTIVES:

1. To evaluate single nucleotide polymorphisms (SNPs) associated with progression-free survival and toxicity in advanced stage epithelial ovarian, peritoneal and fallopian tube cancer using genome wide association studies (GWAS).* II. To evaluate genomic signatures in tumor tissues which are predictive for patient survival in advanced stage epithelial ovarian, peritoneal and fallopian tube cancer.* III. To evaluate the association between serum and plasma biomarkers and response to anti-angiogenesis therapy in advanced stage epithelial ovarian, peritoneal, and fallopian tube cancer.*

NOTE: *As of 02/08/2012, the translational research (TR) portion of this study is complete; patients enrolled after this date will not have TR specimens collected.

IMAGING PRIMARY OBJECTIVES:

1. To determine whether larger changes in the tumor perfusion parameters from baseline timepoint (T0) to early-therapy T2 are prognostic of higher progression-free survival (PFS) rate at 6 months (PFS-6) from enrollment in patients treated with weekly or every-3-week paclitaxel regimens, who are receiving carboplatin with or without bevacizumab.***

IMAGING SECONDARY OBJECTIVES:

1. To determine whether larger changes in tumor perfusion parameters from baseline T0 to intermediate T1 and from T1 to T2 are prognostic of higher PFS-6 in patients treated with weekly or every-3-week paclitaxel regimens, who are receiving carboplatin with or without bevacizumab.*** II. To determine whether larger changes in tumor perfusion parameters values from T0 to T1, T0 to T2, and T1 to T2 are prognostic of better overall survival in all treatment arms.*** III. To assess the association between changes in tumor perfusion parameters before and after chemotherapy initiation (T0 to T1) and subsequent best tumor response according to standard anatomic Response Evaluation Criteria in Solid Tumors (RECIST).*** IV. To assess the association between tumor perfusion parameters before chemotherapy and subsequent best tumor response according to RECIST, PFS-6, and overall survival.*** V. To test the assumption that tumor perfusion parameters are reliable, user-independent, and reproducible parameters of tumor microvascular characteristics; a subgroup of 15 patients will have repeat computed tomography (CT) perfusion studies at the intermediate T1 time point.***

NOTE: ***Patients enrolled after February 8, 2012 must participate in the ACRIN 6695 component at ACRIN-qualified institutions.

OUTLINE: Patients are randomized to 1 of 2 treatment arms (beginning on 04-30-2012, the trial is no longer randomized and the chemotherapy regimen is selected and declared prior to enrolling in the study).

ARM I (adjuvant chemotherapy suboptimally debulked): Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses.

ARM II (neoadjuvant chemotherapy with interval cytoreductive surgery): Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Patients undergo interval cytoreductive surgery between courses 3 and 4.

Patients in both arms may receive optional** bevacizumab IV over 30-90 minutes on day 1 beginning in course 2. Courses of bevacizumab repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients in Arm II receive bevacizumab during courses 2, 5, and 6 only.

NOTE: **Before enrolling onto this study, each patient chooses whether the study treatment will include concurrent and maintenance bevacizumab.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 692 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: GOG-0262: A Phase III Trial of Every-3-Weeks Paclitaxel Versus Dose Dense Weekly Paclitaxel in Combination With Carboplatin With or Without Concurrent and Consolidation Bevacizumab (NSC #704865) in the Treatment of Primary Stage II, III or IV Epithelial Ovarian, Peritoneal or Fallopian Tube Cancer and ACRIN 6695: Perfusion CT Imaging to Evaluate Treatment Response in Patients Participating in GOG-0262
• Actual Study Start Date: Sep 27, 2010
• Actual Primary Completion Date: Dec 1, 2015
• Anticipated Study Completion Date: Jun 7, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (adjuvant chemotherapy suboptimally debulked) Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses.	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 ; Procedure: Computed Tomography; Correlative studies; Other Names: CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized Tomography CT CT Scan tomography ; Drug: Paclitaxel; Given IV; Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat ; Procedure: Therapeutic Conventional Surgery; Undergo surgery
Experimental: Arm II (neoadjuvant chemotherapy) Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Patients undergo interval cytoreductive surgery between courses 3 and 4.	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 ; Procedure: Computed Tomography; Correlative studies; Other Names: CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized Tomography CT CT Scan tomography ; Drug: Paclitaxel; Given IV; Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat ; Procedure: Therapeutic Conventional Surgery; Undergo surgery

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival [The timeframe is from enrollment onto the study up to 3 years following enrollment.]

   First progression or death for weekly paclitaxel treatment relative to standard 3 week paclitaxel. Progression is defined using response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Secondary Outcome Measures

1. Median Duration of First Quartile Survival [The timeframe is from enrollment onto the study up to 3 years after enrollment]

   First Quartile Overall Survival

2. Quality of Life Score as Measured by Functional Assessment of Cancer Therapy-Ovary-Total Outcome Index (Fact-O TOI) [18 weeks after enrolling on the study, which is the time it takes to complete 6 cycles of treatment plus 3 weeks]

   Mean quality of life score after 6 cycles of study treatment estimated from a mixed model. The FACT-O-TOI is composed of three subscales: Physical Well Being (PWB) (7 Items), Functional Well Being (FWB) (7 items), and Ovarian Cancer Subscale (OCS) (12 items). Each item in the FACT-O TOI are scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). A subscale score is computed as long as more than 50% of subscale items have been answered. A Total score of the FACT-O TOI is the summation of the three subscale scores; if more than 80% of the FACT-O TOI items provide valid responses and all three subscales have valid scores. A score of the FACT-O TOI is ranged 0-104 with a larger score indicating a more preferred state of health-related quality of life (HRQOL)

Other Outcome Measures

1. Changes in the Tumor Perfusion Parameters as Quantified by Vascularity or Blood Volume; Perfusion or Blood Flow; Mean Transit Time; and Microvascular Permeability or Permeability Surface Area Product [Baseline (T0) up to 10 days after the start of course 2 (T2)]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Primary Surgery and Neoadjuvant Chemotherapy with Interval Cytoreductive Surgery

Patients:

• Patients must have measurable disease; at least one target lesion must have a minimum length of 1 cm in both the long and short axis (determined at the local site); for primary surgery patients, if no radiographic evidence of measurable disease is obtained prior to registration this can be based on surgical findings; imaging then would need to be completed in the 14 days between Gynecology Oncology Group (GOG) registration and chemotherapy initiation

• After GOG registration, the American College of Radiology [ACR] Imaging Core Laboratory will confirm target lesion as required per protocol; the GOG-eligibility (RECIST) scan and baseline T0 perfusion CT scans will be reviewed prior to the intermediate T1 perfusion CT time point

• Primary Surgery Patients:

• Patients with a histologic diagnosis of epithelial ovarian cancer, peritoneal primary carcinoma or fallopian tube cancer, stage II -IV suboptimally debulked (any residual disease > 1 cm); International Federation of Gynecology and Obstetrics (FIGO) stage is assessed following the completion of initial abdominal surgery, appropriate imaging studies and with appropriate tissue available for histologic evaluation; the minimum surgery required is an abdominal surgery providing tissue for histologic evaluation and establishing and documenting the primary site and stage; if additional surgery was performed, it should have been in accordance with appropriate surgery for ovarian or peritoneal carcinoma described in the GOG Surgical Procedures Manual

• Neoadjuvant Chemotherapy (NAC) with Interval Cytoreductive Surgery (ICS) Patients:

• For patients undergoing NAC-ICS, a core tissue (not fine needle aspiration) biopsy is required; the tissue must be consistent with a Müllerian origin; patients will require documentation of at least stage II or extraovarian sites of disease acquired via imaging or surgery (without attempt at cytoreduction)

• Patients with the following histologic epithelial cell types are eligible: serous, endometrioid, clear cell, mucinous adenocarcinoma, undifferentiated carcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma not otherwise specified (N.O.S.); however, the histologic features of the tumor must be compatible with a primary Müllerian epithelial adenocarcinoma; patients may have co-existing fallopian tube carcinoma in-situ so long as the primary origin of invasive tumor is ovarian, peritoneal or fallopian tube; of note, patients with clear cell and mucinous tumors will be eligible unless there is a higher priority protocol

• Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl; this ANC cannot have been induced or supported by granulocyte colony stimulating factors

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

• Creatinine =< 1.5 x institutional upper limit normal (ULN)

• Bilirubin less than or equal to 1.5 x ULN

• Serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 3 x ULN

• Alkaline phosphatase less than or equal to 2.5 x ULN

• Neuropathy (sensory or motor) less than or equal to Common Terminology Criteria for Adverse Events (CTCAE) grade 1

• Patients must have a GOG performance status of 0, 1, or 2

• Patients must be entered within 12 weeks of diagnostic/staging surgery

• Patients who have met the pre-entry requirements

• An approved informed consent and authorization permitting release of personal health information and must be signed by the patient or guardian

• Only applies for patients who elect to receive bevacizumab:

• Patients in this trial may receive ovarian estrogen +/- progestin replacement therapy as indicated at the lowest effective dose(s) for control of menopausal symptoms at any time, but not high-dose progestins for management of anorexia while on protocol-directed therapy or prior to disease progression due to thrombophlebitis risk

• Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thromboembolus) and a partial prothrombin time (PTT) < 1.2 times the upper limit of normal; (heparin, lovenox or alternative anticoagulants are acceptable)

• All patients enrolled into GOG-0262 at sites where ACRIN 6695 is open will be enrolled in the advanced imaging protocol; patients receiving adjuvant or neoadjuvant chemotherapy are eligible for ACRIN 6695; the following sentence does not apply to those patients entered after 02/08/2012: if a patient declines to participate in the perfusion imaging portion of the protocol, a clinical rationale for declination of imaging form will be completed as part of the data submission for ACRIN 6695

• ACRIN 6695 Eligible Patients:

• Confirmation of ACRIN 6695 eligibility after the baseline T0 perfusion computed tomography (CT) will be assessed by the ACR Imaging Core Lab: At least one target lesion must have a minimum length of 1 cm in both the long and short axis (as determined by the local site), at least half of the target lesion must have attenuation greater than or equal to 10 Hounsfield Units (HU) on the unenhanced CT, and at least half of the lesion must have maximum enhancement greater than or equal to 5 HU in the perfusion CT scan (as determined by the ACR Imaging Core Lab)

Exclusion Criteria:

• Patients with a current diagnosis of borderline epithelial ovarian tumor (formerly "tumors of low malignant potential") or recurrent invasive epithelial ovarian, primary peritoneal or fallopian tube cancer treated with surgery only (such as patients with stage I-A or I-B low grade epithelial ovarian or fallopian tube cancers) are not eligible; patients with a prior diagnosis of a borderline tumor that was surgically resected and who subsequently develop an unrelated, new invasive epithelial ovarian, peritoneal primary or fallopian tube cancer are eligible, provided that they have not received prior chemotherapy for any ovarian tumor

• Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis; 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 including neo-adjuvant chemotherapy for their ovarian, primary peritoneal or fallopian tube cancer; 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 who have received any targeted therapy (including but not limited to vaccines, antibodies, tyrosine kinase inhibitors) or hormonal therapy for management of their epithelial ovarian, fallopian tube or peritoneal primary cancer

• Patients with synchronous primary endometrial cancer, or a past history of primary endometrial cancer, unless all of the following conditions are met: stage not greater than I-A, grade 1 or 2, no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell or other FIGO grade 3 lesions

• With the exception of non-melanoma skin cancer, patients with other invasive malignancies who had (or have) any evidence of the other cancer present within the last five years or whose previous cancer treatment contraindicates this protocol therapy

• Patients with acute hepatitis or active infection that requires parenteral antibiotics

• Patients with clinically significant cardiovascular disease; this includes:

• Myocardial infarction or unstable angina < 6 months prior to registration

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

• Serious cardiac arrhythmia requiring medication; this does not include asymptomatic, atrial fibrillation with controlled ventricular rate

• Patients who are pregnant or nursing; patients of childbearing potential must agree to use contraceptive measures during study therapy and for at least six months after completion of bevacizumab therapy

• Patients who have received prior therapy with any anti-vascular endothelial growth factor (VEGF) drug, including bevacizumab

• Patients with medical history or conditions not otherwise previously specified which in the opinion of the investigator should exclude participation in this study; the investigator should feel free to consult the Statistical and Data Center (SDC) randomization desk for uncertainty in this regard

• Patients with known allergy to cremophor or polysorbate 80

• Only applies to patients who elect to receive bevacizumab:

• Patients with serious non-healing wound, ulcer, or bone fracture; this includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days; patients with granulating incisions healing by secondary intention with no evidence of fascial dehiscence or infection are eligible but require weekly wound examinations

• 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, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study

• Patients with CTCAE grade 2 or greater peripheral vascular disease (at least brief [< 24 hours] episodes of ischemia managed non-surgically and without permanent deficit)

• Patients with a history of CVA within six months

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

• Patients with clinically significant proteinuria; urine protein should be screened by urine protein-creatinine ratio (UPCR); the UPCR has been found to correlate directly with the amount of protein excreted in a 24 hour urine collection; specifically, a UPCR of 1.0 is equivalent to 1.0 gram of protein in a 24-hour urine collection; obtain at least 4 ml of a random urine sample in a sterile container (does not have to be a 24-hour urine); send sample to lab with request for urine protein and creatinine levels (separate requests); the lab will measure protein concentration (mg/dL) and creatinine concentration (mg/dL); the UPCR is derived as follows: protein concentration (mg/dL)/creatinine (mg/dL); patients must have a UPCR < 1.0 to allow participation in the study

• Patients with or with anticipation of invasive procedures as defined below:

• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of bevacizumab therapy (cycle 2)

• Major surgical procedure anticipated during the course of the study; this includes, but is not limited to abdominal surgery (laparotomy or laparoscopy) prior to disease progression such as colostomy or enterostomy reversal, secondary cytoreductive surgery, or second look surgery; please consult with the SDC Randomization Desk prior to patient entry for any questions related to the classification of surgical procedures

• Any tissue biopsy, such as a core biopsy, within 7 days prior to the first date of bevacizumab therapy (cycle 2)

• Patients with clinical symptoms or signs of gastrointestinal obstruction and who require parenteral hydration and/or nutrition

• Patients with metastasis tumor in the parenchyma of the liver or lungs with proximity to large vessels which could make the patients at high risk of lethal hemorrhage during treatment with bevacizumab (ie. hemoptysis, liver rupture)

• ACRIN 6695 Ineligible Patients:

• Patients with contraindication to iodinated contrast for perfusion CT imaging

• Patients who receive Metformin within 48 hours before perfusion CT imaging

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
2	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama	United States	36688
3	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
4	Saint Joseph's Hospital and Medical Center	Phoenix	Arizona	United States	85013
5	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
6	University of Arizona Cancer Center-Orange Grove Campus	Tucson	Arizona	United States	85704
7	Banner University Medical Center - Tucson	Tucson	Arizona	United States	85719
8	University of Arizona Cancer Center-North Campus	Tucson	Arizona	United States	85719
9	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas	United States	71913
10	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
11	Kaiser Permanente-Deer Valley Medical Center	Antioch	California	United States	94531
12	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
13	East Bay Radiation Oncology Center	Castro Valley	California	United States	94546
14	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California	United States	94546
15	John Muir Medical Center-Concord Campus	Concord	California	United States	94520
16	Bay Area Breast Surgeons Inc	Emeryville	California	United States	94608
17	Kaiser Permanente-Fremont	Fremont	California	United States	94538
18	Valley Medical Oncology Consultants-Fremont	Fremont	California	United States	94538
19	Kaiser Permanente-Fresno	Fresno	California	United States	93720
20	Marin Cancer Care Inc	Greenbrae	California	United States	94904
21	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
22	Long Beach Memorial Medical Center-Todd Cancer Institute	Long Beach	California	United States	90806
23	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
24	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
25	UCLA / Jonsson Comprehensive Cancer Center	Los Angeles	California	United States	90095
26	Contra Costa Regional Medical Center	Martinez	California	United States	94553-3156
27	El Camino Hospital	Mountain View	California	United States	94040
28	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California	United States	94040
29	Highland General Hospital	Oakland	California	United States	94602
30	Alta Bates Summit Medical Center - Summit Campus	Oakland	California	United States	94609
31	Bay Area Tumor Institute	Oakland	California	United States	94609
32	Hematology and Oncology Associates-Oakland	Oakland	California	United States	94609
33	Tom K Lee Inc	Oakland	California	United States	94609
34	Kaiser Permanente Oakland-Broadway	Oakland	California	United States	94611
35	Kaiser Permanente-Oakland	Oakland	California	United States	94611
36	Stanford Cancer Institute Palo Alto	Palo Alto	California	United States	94304
37	Kaiser Permanente-Rancho Cordova Cancer Center	Rancho Cordova	California	United States	95670
38	Kaiser Permanente-Redwood City	Redwood City	California	United States	94063
39	Kaiser Permanente-Richmond	Richmond	California	United States	94801
40	Rohnert Park Cancer Center	Rohnert Park	California	United States	94928
41	Kaiser Permanente-Roseville	Roseville	California	United States	95661
42	Sutter Roseville Medical Center	Roseville	California	United States	95661
43	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California	United States	95678
44	Sutter Medical Center Sacramento	Sacramento	California	United States	95816
45	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
46	Kaiser Permanente-South Sacramento	Sacramento	California	United States	95823
47	South Sacramento Cancer Center	Sacramento	California	United States	95823
48	Kaiser Permanente - Sacramento	Sacramento	California	United States	95825
49	Sharp Memorial Hospital	San Diego	California	United States	92123
50	Kaiser Permanente-San Francisco	San Francisco	California	United States	94115
51	UCSF Medical Center-Mount Zion	San Francisco	California	United States	94115
52	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California	United States	95119
53	Kaiser Permanente San Leandro	San Leandro	California	United States	94577
54	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California	United States	94806
55	Kaiser Permanente-San Rafael	San Rafael	California	United States	94903
56	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California	United States	95051
57	Kaiser Permanente-Santa Rosa	Santa Rosa	California	United States	95403
58	Kaiser Permanente Cancer Treatment Center	South San Francisco	California	United States	94080
59	Kaiser Permanente-South San Francisco	South San Francisco	California	United States	94080
60	Kaiser Permanente-Stockton	Stockton	California	United States	95210
61	Olive View-University of California Los Angeles Medical Center	Sylmar	California	United States	91342
62	Kaiser Permanente Medical Center-Vacaville	Vacaville	California	United States	95688
63	Kaiser Permanente-Vallejo	Vallejo	California	United States	94589
64	Kaiser Permanente-Walnut Creek	Walnut Creek	California	United States	94596
65	John Muir Medical Center-Walnut Creek	Walnut Creek	California	United States	94598
66	University of Colorado Hospital	Aurora	Colorado	United States	80045
67	Kaiser Permanente-Franklin	Denver	Colorado	United States	80205
68	Rocky Mountain Gynecologic Oncology PC	Englewood	Colorado	United States	80110
69	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
70	Kaiser Permanente-Rock Creek	Lafayette	Colorado	United States	80026
71	Hartford HealthCare - Saint Vincent's Medical Center	Bridgeport	Connecticut	United States	06606
72	Danbury Hospital	Danbury	Connecticut	United States	06810
73	Hartford Hospital	Hartford	Connecticut	United States	06102
74	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut	United States	06105
75	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
76	Yale University	New Haven	Connecticut	United States	06520
77	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut	United States	06360
78	Stamford Hospital/Bennett Cancer Center	Stamford	Connecticut	United States	06904
79	Beebe Medical Center	Lewes	Delaware	United States	19958
80	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
81	MedStar Washington Hospital Center	Washington	District of Columbia	United States	20010
82	Sibley Memorial Hospital	Washington	District of Columbia	United States	20016
83	Morton Plant Hospital	Clearwater	Florida	United States	33756
84	Broward Health Medical Center	Fort Lauderdale	Florida	United States	33316
85	Florida Gynecologic Oncology	Fort Myers	Florida	United States	33905
86	Southeast Gynecologic Oncology Associates	Jacksonville	Florida	United States	32204
87	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224-9980
88	The Watson Clinic	Lakeland	Florida	United States	33805
89	AdventHealth Orlando	Orlando	Florida	United States	32803
90	Orlando Health Cancer Institute	Orlando	Florida	United States	32806
91	Women's Cancer Associates	Saint Petersburg	Florida	United States	33713
92	Northside Hospital	Atlanta	Georgia	United States	30342
93	Northeast Georgia Medical Center-Gainesville	Gainesville	Georgia	United States	30501
94	Central Georgia Gynecologic Oncology	Macon	Georgia	United States	31201
95	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
96	Pali Momi Medical Center	'Aiea	Hawaii	United States	96701
97	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii	United States	96813
98	Queen's Medical Center	Honolulu	Hawaii	United States	96813
99	Straub Clinic and Hospital	Honolulu	Hawaii	United States	96813
100	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
101	Queen's Cancer Center - Kuakini	Honolulu	Hawaii	United States	96817
102	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii	United States	96817
103	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii	United States	96819
104	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
105	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii	United States	96766
106	Maui Memorial Medical Center	Wailuku	Hawaii	United States	96793
107	Pacific Cancer Institute of Maui	Wailuku	Hawaii	United States	96793
108	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
109	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho	United States	83854
110	Rush - Copley Medical Center	Aurora	Illinois	United States	60504
111	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
112	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
113	Graham Hospital Association	Canton	Illinois	United States	61520
114	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
115	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
116	Memorial Hospital	Carthage	Illinois	United States	62321
117	Northwestern University	Chicago	Illinois	United States	60611
118	John H Stroger Jr Hospital of Cook County	Chicago	Illinois	United States	60612
119	Rush University Medical Center	Chicago	Illinois	United States	60612
120	Presence Resurrection Medical Center	Chicago	Illinois	United States	60631
121	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
122	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
123	Heartland Cancer Research NCORP	Decatur	Illinois	United States	62526
124	Elmhurst Memorial Hospital	Elmhurst	Illinois	United States	60126
125	Eureka Hospital	Eureka	Illinois	United States	61530
126	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
127	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
128	Illinois CancerCare-Havana	Havana	Illinois	United States	62644
129	Mason District Hospital	Havana	Illinois	United States	62644
130	Sudarshan K Sharma MD Limited-Gynecologic Oncology	Hinsdale	Illinois	United States	60521
131	Presence Saint Mary's Hospital	Kankakee	Illinois	United States	60901
132	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
133	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
134	Mcdonough District Hospital	Macomb	Illinois	United States	61455
135	Loyola University Medical Center	Maywood	Illinois	United States	60153
136	Garneau, Stewart C MD (UIA Investigator)	Moline	Illinois	United States	61265
137	Porubcin, Michael MD (UIA Investigator)	Moline	Illinois	United States	61265
138	Spector, David MD (UIA Investigator)	Moline	Illinois	United States	61265
139	Trinity Medical Center	Moline	Illinois	United States	61265
140	Holy Family Medical Center	Monmouth	Illinois	United States	61462
141	Illinois CancerCare-Monmouth	Monmouth	Illinois	United States	61462
142	Bromenn Regional Medical Center	Normal	Illinois	United States	61761
143	Carle Cancer Institute Normal	Normal	Illinois	United States	61761
144	Illinois CancerCare-Community Cancer Center	Normal	Illinois	United States	61761
145	Advocate Christ Medical Center	Oak Lawn	Illinois	United States	60453-2699
146	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
147	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois	United States	61350
148	Advocate Lutheran General Hospital	Park Ridge	Illinois	United States	60068
149	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
150	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
151	Proctor Hospital	Peoria	Illinois	United States	61614
152	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
153	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
154	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
155	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
156	Illinois Valley Hospital	Peru	Illinois	United States	61354
157	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
158	Perry Memorial Hospital	Princeton	Illinois	United States	61356
159	Illinois CancerCare-Spring Valley	Spring Valley	Illinois	United States	61362
160	Memorial Medical Center	Springfield	Illinois	United States	62781
161	Carle Cancer Center	Urbana	Illinois	United States	61801
162	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois	United States	60555
163	Northwestern Medicine Central DuPage Hospital	Winfield	Illinois	United States	60190
164	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana	United States	46107
165	Elkhart Clinic	Elkhart	Indiana	United States	46514-2098
166	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana	United States	46514
167	Elkhart General Hospital	Elkhart	Indiana	United States	46515
168	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana	United States	46845
169	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
170	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana	United States	46260
171	Community Howard Regional Health	Kokomo	Indiana	United States	46904
172	IU Health La Porte Hospital	La Porte	Indiana	United States	46350
173	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana	United States	46360
174	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana	United States	46545
175	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana	United States	46545
176	The Community Hospital	Munster	Indiana	United States	46321
177	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana	United States	46563
178	Reid Health	Richmond	Indiana	United States	47374
179	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
180	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana	United States	46601
181	South Bend Clinic	South Bend	Indiana	United States	46617
182	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46628
183	Michiana Hematology Oncology PC-Westville	Westville	Indiana	United States	46391
184	McFarland Clinic PC - Ames	Ames	Iowa	United States	50010
185	Constantinou, Costas L MD (UIA Investigator)	Bettendorf	Iowa	United States	52722
186	Mercy Hospital	Cedar Rapids	Iowa	United States	52403
187	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
188	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa	United States	50325
189	Mercy Cancer Center-West Lakes	Clive	Iowa	United States	50325
190	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
191	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa	United States	50309
192	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
193	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
194	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
195	Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
196	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
197	Mercy Medical Center - North Iowa	Mason City	Iowa	United States	50401
198	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
199	Mercy Medical Center-Sioux City	Sioux City	Iowa	United States	51102
200	Saint Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
201	Methodist West Hospital	West Des Moines	Iowa	United States	50266-7700
202	Mercy Medical Center-West Lakes	West Des Moines	Iowa	United States	50266
203	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
204	Menorah Medical Center	Overland Park	Kansas	United States	66209
205	Saint Luke's South Hospital	Overland Park	Kansas	United States	66213
206	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas	United States	66208
207	Saint Elizabeth Healthcare Edgewood	Edgewood	Kentucky	United States	41017
208	Baptist Health Lexington	Lexington	Kentucky	United States	40503
209	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
210	Norton Hospital Pavilion and Medical Campus	Louisville	Kentucky	United States	40202
211	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky	United States	40202
212	Pikeville Medical Center	Pikeville	Kentucky	United States	41501
213	Woman's Hospital	Baton Rouge	Louisiana	United States	70817
214	Louisiana State University Health Science Center	New Orleans	Louisiana	United States	70112
215	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
216	University Medical Center New Orleans	New Orleans	Louisiana	United States	70112
217	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
218	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana	United States	71103
219	Highland Clinic	Shreveport	Louisiana	United States	71105
220	Eastern Maine Medical Center	Bangor	Maine	United States	04401
221	Maine Medical Center-Bramhall Campus	Portland	Maine	United States	04102
222	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
223	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
224	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
225	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland	United States	21237
226	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
227	University of Maryland Shore Medical Center at Easton	Easton	Maryland	United States	21601
228	Christiana Care - Union Hospital	Elkton	Maryland	United States	21921
229	Holy Cross Hospital	Silver Spring	Maryland	United States	20910
230	Sturdy Memorial Hospital	Attleboro	Massachusetts	United States	02703
231	Tufts Medical Center	Boston	Massachusetts	United States	02111
232	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
233	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
234	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
235	Lahey Hospital and Medical Center	Burlington	Massachusetts	United States	01805
236	Holy Family Hospital	Methuen	Massachusetts	United States	01844
237	Baystate Medical Center	Springfield	Massachusetts	United States	01199
238	UMass Memorial Medical Center - Memorial Division	Worcester	Massachusetts	United States	01605
239	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan	United States	48106
240	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
241	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
242	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan	United States	49307
243	Beaumont Hospital - Dearborn	Dearborn	Michigan	United States	48124
244	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
245	Henry Ford Hospital	Detroit	Michigan	United States	48202
246	Ascension Saint John Hospital	Detroit	Michigan	United States	48236
247	Green Bay Oncology - Escanaba	Escanaba	Michigan	United States	49829
248	Hurley Medical Center	Flint	Michigan	United States	48503
249	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan	United States	48532
250	Genesys Regional Medical Center	Grand Blanc	Michigan	United States	48439
251	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan	United States	49503
252	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
253	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
254	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan	United States	49801
255	Allegiance Health	Jackson	Michigan	United States	49201
256	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
257	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
258	Borgess Medical Center	Kalamazoo	Michigan	United States	49048
259	Sparrow Hospital	Lansing	Michigan	United States	48912
260	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan	United States	48154
261	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
262	Lakeland Hospital Niles	Niles	Michigan	United States	49120
263	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
264	Lake Huron Medical Center	Port Huron	Michigan	United States	48060
265	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
266	Ascension Saint Mary's Hospital	Saginaw	Michigan	United States	48601
267	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan	United States	49085
268	Marie Yeager Cancer Center	Saint Joseph	Michigan	United States	49085
269	Ascension Providence Hospitals - Southfield	Southfield	Michigan	United States	48075
270	Munson Medical Center	Traverse City	Michigan	United States	49684
271	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
272	Metro Health Hospital	Wyoming	Michigan	United States	49519
273	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota	United States	56601
274	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota	United States	56401
275	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
276	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
277	Essentia Health Cancer Center	Duluth	Minnesota	United States	55805
278	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota	United States	55805
279	Miller-Dwan Hospital	Duluth	Minnesota	United States	55805
280	Saint Luke's Hospital of Duluth	Duluth	Minnesota	United States	55805
281	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
282	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota	United States	56537
283	Unity Hospital	Fridley	Minnesota	United States	55432
284	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
285	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
286	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
287	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
288	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
289	New Ulm Medical Center	New Ulm	Minnesota	United States	56073
290	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
291	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905
292	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
293	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
294	Park Nicollet Frauenshuh Cancer Center	Saint Louis Park	Minnesota	United States	55426
295	Regions Hospital	Saint Paul	Minnesota	United States	55101
296	United Hospital	Saint Paul	Minnesota	United States	55102
297	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
298	Lakeview Hospital	Stillwater	Minnesota	United States	55082
299	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
300	Rice Memorial Hospital	Willmar	Minnesota	United States	56201
301	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
302	Saint Dominic-Jackson Memorial Hospital	Jackson	Mississippi	United States	39216
303	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
304	Freeman Health System	Joplin	Missouri	United States	64804
305	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
306	Saint Joseph Health Center	Kansas City	Missouri	United States	64114
307	North Kansas City Hospital	Kansas City	Missouri	United States	64116
308	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri	United States	64118
309	Research Medical Center	Kansas City	Missouri	United States	64132
310	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
311	Liberty Radiation Oncology Center	Liberty	Missouri	United States	64068
312	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
313	Saint Joseph Oncology Inc	Saint Joseph	Missouri	United States	64507
314	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
315	Cancer Research for the Ozarks NCORP	Springfield	Missouri	United States	65804
316	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
317	CoxHealth South Hospital	Springfield	Missouri	United States	65807
318	Billings Clinic Cancer Center	Billings	Montana	United States	59101
319	Saint Vincent Healthcare	Billings	Montana	United States	59101
320	Montana Cancer Consortium NCORP	Billings	Montana	United States	59102
321	Saint Vincent Frontier Cancer Center	Billings	Montana	United States	59102
322	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
323	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
324	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
325	Great Falls Clinic	Great Falls	Montana	United States	59405
326	Northern Montana Hospital	Havre	Montana	United States	59501
327	Saint Peter's Community Hospital	Helena	Montana	United States	59601
328	Glacier Oncology PLLC	Kalispell	Montana	United States	59901
329	Kalispell Medical Oncology	Kalispell	Montana	United States	59901
330	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
331	Montana Cancer Specialists	Missoula	Montana	United States	59802
332	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
333	CHI Health Good Samaritan	Kearney	Nebraska	United States	68847
334	Nebraska Cancer Research Center	Lincoln	Nebraska	United States	68510
335	Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
336	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
337	Alegent Health Immanuel Medical Center	Omaha	Nebraska	United States	68122
338	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
339	Alegent Health Lakeside Hospital	Omaha	Nebraska	United States	68130
340	Creighton University Medical Center	Omaha	Nebraska	United States	68131
341	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
342	Women's Cancer Center of Nevada	Las Vegas	Nevada	United States	89106
343	Center of Hope at Renown Medical Center	Reno	Nevada	United States	89502
344	Renown Regional Medical Center	Reno	Nevada	United States	89502
345	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
346	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
347	Morristown Medical Center	Morristown	New Jersey	United States	07960
348	Virtua Memorial	Mount Holly	New Jersey	United States	08060
349	Jersey Shore Medical Center	Neptune	New Jersey	United States	07753
350	Saint Luke's Hospital-Warren Campus	Phillipsburg	New Jersey	United States	08865
351	Valley Hospital	Ridgewood	New Jersey	United States	07450
352	Overlook Hospital	Summit	New Jersey	United States	07902
353	Inspira Medical Center Vineland	Vineland	New Jersey	United States	08360
354	Virtua Voorhees	Voorhees	New Jersey	United States	08043
355	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
356	Southwest Gynecologic Oncology Associates Inc	Albuquerque	New Mexico	United States	87106
357	Memorial Medical Center - Las Cruces	Las Cruces	New Mexico	United States	88011
358	Women's Cancer Care Associates LLC	Albany	New York	United States	12208
359	Island Gynecologic Oncology	Brightwaters	New York	United States	11718
360	Montefiore Medical Center-Einstein Campus	Bronx	New York	United States	10461
361	State University of New York Downstate Medical Center	Brooklyn	New York	United States	11203
362	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
363	Queens Hospital Center	Jamaica	New York	United States	11432
364	Northwell Health/Center for Advanced Medicine	Lake Success	New York	United States	11042
365	North Shore University Hospital	Manhasset	New York	United States	11030
366	Garnet Health Medical Center	Middletown	New York	United States	10940
367	NYU Winthrop Hospital	Mineola	New York	United States	11501
368	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
369	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
370	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
371	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
372	Staten Island University Hospital	Staten Island	New York	United States	10305
373	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
374	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
375	Hope Women's Cancer Centers-Asheville	Asheville	North Carolina	United States	28816
376	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina	United States	27215
377	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
378	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
379	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
380	Duke University Medical Center	Durham	North Carolina	United States	27710
381	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
382	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
383	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina	United States	28374
384	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
385	New Hanover Regional Medical Center/Zimmer Cancer Center	Wilmington	North Carolina	United States	28401
386	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
387	Mid Dakota Clinic	Bismarck	North Dakota	United States	58501
388	Saint Alexius Medical Center	Bismarck	North Dakota	United States	58501
389	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
390	Sanford Broadway Medical Center	Fargo	North Dakota	United States	58122
391	Sanford Clinic North-Fargo	Fargo	North Dakota	United States	58122
392	Sanford Roger Maris Cancer Center	Fargo	North Dakota	United States	58122
393	Summa Health System - Akron Campus	Akron	Ohio	United States	44304
394	Cleveland Clinic Akron General	Akron	Ohio	United States	44307
395	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
396	Aultman Health Foundation	Canton	Ohio	United States	44710
397	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
398	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio	United States	45219
399	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio	United States	45220
400	Case Western Reserve University	Cleveland	Ohio	United States	44106
401	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
402	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
403	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
404	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
405	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
406	Columbus NCI Community Oncology Research Program	Columbus	Ohio	United States	43215
407	Grant Medical Center	Columbus	Ohio	United States	43215
408	The Mark H Zangmeister Center	Columbus	Ohio	United States	43219
409	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
410	Doctors Hospital	Columbus	Ohio	United States	43228
411	Grandview Hospital	Dayton	Ohio	United States	45405
412	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
413	Miami Valley Hospital	Dayton	Ohio	United States	45409
414	Miami Valley Hospital North	Dayton	Ohio	United States	45415
415	Dayton NCI Community Oncology Research Program	Dayton	Ohio	United States	45459
416	Grady Memorial Hospital	Delaware	Ohio	United States	43015
417	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
418	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
419	Wayne Hospital	Greenville	Ohio	United States	45331
420	Kettering Medical Center	Kettering	Ohio	United States	45429
421	Fairfield Medical Center	Lancaster	Ohio	United States	43130
422	Saint Rita's Medical Center	Lima	Ohio	United States	45801
423	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
424	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
425	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio	United States	44060
426	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
427	Licking Memorial Hospital	Newark	Ohio	United States	43055
428	Southern Ohio Medical Center	Portsmouth	Ohio	United States	45662
429	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
430	Upper Valley Medical Center	Troy	Ohio	United States	45373
431	Saint Ann's Hospital	Westerville	Ohio	United States	43081
432	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
433	Greene Memorial Hospital	Xenia	Ohio	United States	45385
434	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio	United States	43701
435	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
436	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma	United States	74146
437	Saint Charles Health System	Bend	Oregon	United States	97701
438	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon	United States	97210
439	Compass Oncology Rose Quarter	Portland	Oregon	United States	97227
440	Oregon Health and Science University	Portland	Oregon	United States	97239
441	Jefferson Abington Hospital	Abington	Pennsylvania	United States	19001
442	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
443	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania	United States	18015
444	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
445	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania	United States	19026
446	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
447	Lancaster General Hospital	Lancaster	Pennsylvania	United States	17602
448	Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301
449	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
450	Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19107
451	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
452	Temple University Hospital	Philadelphia	Pennsylvania	United States	19140
453	Phoenixville Hospital	Phoenixville	Pennsylvania	United States	19460
454	UPMC-Magee Womens Hospital	Pittsburgh	Pennsylvania	United States	15213
455	West Penn Hospital	Pittsburgh	Pennsylvania	United States	15224
456	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania	United States	15232
457	Mercy Hospital	Scranton	Pennsylvania	United States	18501
458	Hematology and Oncology Associates of North East Pennsylvania	Scranton	Pennsylvania	United States	18508
459	Scranton Hematology Oncology	Scranton	Pennsylvania	United States	18510
460	Associates In Hematology Oncology PC-Upland	Upland	Pennsylvania	United States	19013
461	Chester County Hospital	West Chester	Pennsylvania	United States	19380
462	Reading Hospital	West Reading	Pennsylvania	United States	19611
463	Lankenau Medical Center	Wynnewood	Pennsylvania	United States	19096
464	Main Line Health NCORP	Wynnewood	Pennsylvania	United States	19096
465	Women and Infants Hospital	Providence	Rhode Island	United States	02905
466	AnMed Health Cancer Center	Anderson	South Carolina	United States	29621
467	AnMed Health Hospital	Anderson	South Carolina	United States	29621
468	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina	United States	29316
469	Medical University of South Carolina	Charleston	South Carolina	United States	29425
470	Saint Francis Hospital	Greenville	South Carolina	United States	29601
471	Prisma Health Cancer Institute - Faris	Greenville	South Carolina	United States	29605
472	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina	United States	29615
473	Spartanburg Medical Center	Spartanburg	South Carolina	United States	29303
474	Black Hills Obstetrics and Gynecology	Rapid City	South Dakota	United States	57701
475	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota	United States	57104
476	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
477	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
478	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee	United States	37660
479	University of Tennessee - Knoxville	Knoxville	Tennessee	United States	37920
480	Parkland Memorial Hospital	Dallas	Texas	United States	75235
481	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
482	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
483	University of Texas Medical Branch	Galveston	Texas	United States	77555-0565
484	Lyndon Baines Johnson General Hospital	Houston	Texas	United States	77026-1967
485	Houston Methodist Hospital	Houston	Texas	United States	77030
486	M D Anderson Cancer Center	Houston	Texas	United States	77030
487	Scott and White Memorial Hospital	Temple	Texas	United States	76508
488	American Fork Hospital / Huntsman Intermountain Cancer Center	American Fork	Utah	United States	84003
489	Sandra L Maxwell Cancer Center	Cedar City	Utah	United States	84720
490	Logan Regional Hospital	Logan	Utah	United States	84321
491	Intermountain Medical Center	Murray	Utah	United States	84107
492	McKay-Dee Hospital Center	Ogden	Utah	United States	84403
493	Utah Valley Regional Medical Center	Provo	Utah	United States	84604
494	Saint George Regional Medical Center	Saint George	Utah	United States	84770
495	Intermountain Health Care	Salt Lake City	Utah	United States	84103
496	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah	United States	84106
497	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
498	LDS Hospital	Salt Lake City	Utah	United States	84143
499	University of Vermont Medical Center	Burlington	Vermont	United States	05401
500	Northern Virginia Pelvic Surgery Associates	Annandale	Virginia	United States	22003
501	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908
502	Danville Regional Medical Center	Danville	Virginia	United States	24541
503	Hematology Oncology Associates of Fredericksburg Inc	Fredericksburg	Virginia	United States	22408
504	Virginia Oncology Associates-Hampton	Hampton	Virginia	United States	23666
505	Centra Lynchburg Hematology-Oncology Clinic Inc	Lynchburg	Virginia	United States	24501
506	Virginia Oncology Associates - Lake Wright	Norfolk	Virginia	United States	23502
507	Southwest VA Regional Cancer Center	Norton	Virginia	United States	24273
508	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
509	Carilion Clinic Gynecological Oncology	Roanoke	Virginia	United States	24016
510	PeaceHealth Medical Group PC	Bellingham	Washington	United States	98226
511	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington	United States	98310
512	Harrison Medical Center	Bremerton	Washington	United States	98310
513	Providence Regional Cancer Partnership	Everett	Washington	United States	98201
514	Skagit Regional Health Cancer Care Center	Mount Vernon	Washington	United States	98274
515	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington	United States	98370
516	Virginia Mason Medical Center	Seattle	Washington	United States	98101
517	Pacific Gynecology Specialists	Seattle	Washington	United States	98104
518	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
519	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
520	Kaiser Permanente Washington	Seattle	Washington	United States	98112
521	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
522	University of Washington Medical Center - Northwest	Seattle	Washington	United States	98133
523	University of Washington Medical Center - Montlake	Seattle	Washington	United States	98195
524	Olympic Medical Cancer Care Center	Sequim	Washington	United States	98384
525	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
526	MultiCare Deaconess Cancer and Blood Specialty Center - Downtown	Spokane	Washington	United States	99204
527	MultiCare Tacoma General Hospital	Tacoma	Washington	United States	98405
528	Saint Joseph Medical Center	Tacoma	Washington	United States	98405
529	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington	United States	99362
530	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801
531	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington	United States	98902
532	Langlade Hospital and Cancer Center	Antigo	Wisconsin	United States	54409
533	ThedaCare Regional Cancer Center	Appleton	Wisconsin	United States	54911
534	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin	United States	54729
535	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin	United States	54701
536	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
537	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
538	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
539	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin	United States	54303
540	Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
541	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
542	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin	United States	53792
543	Holy Family Memorial Hospital	Manitowoc	Wisconsin	United States	54221
544	Bay Area Medical Center	Marinette	Wisconsin	United States	54143
545	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin	United States	54449
546	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
547	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
548	Aurora Sinai Medical Center	Milwaukee	Wisconsin	United States	53233
549	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin	United States	54548
550	ProHealth D N Greenwald Center	Mukwonago	Wisconsin	United States	53149
551	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin	United States	53066
552	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin	United States	54154
553	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin	United States	54904
554	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin	United States	54501
555	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin	United States	54868
556	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin	United States	53081
557	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
558	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
559	Aurora Medical Center in Summit	Summit	Wisconsin	United States	53066
560	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin	United States	54241
561	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin	United States	53188
562	Aspirus Regional Cancer Center	Wausau	Wisconsin	United States	54401
563	Aurora West Allis Medical Center	West Allis	Wisconsin	United States	53227
564	Diagnostic and Treatment Center	Weston	Wisconsin	United States	54476
565	Marshfield Medical Center - Weston	Weston	Wisconsin	United States	54476
566	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin	United States	54494
567	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
568	Welch Cancer Center	Sheridan	Wyoming	United States	82801
569	Odette Cancer Centre- Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
570	Asan Medical Center	Seoul		Korea, Republic of	05505
571	Gangnam Severance Hospital	Seoul		Korea, Republic of	06273
572	Seoul National University Hospital	Seoul		Korea, Republic of	110-744
573	Yongdong Severence Hospital	Seoul		Korea, Republic of	135-720

Sponsors and Collaborators

• National Cancer Institute (NCI)
• NRG Oncology

Investigators

• Principal Investigator: John K Chan, NRG Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01167712
• Other Study ID Numbers: NCI-2011-03812; NCI-2011-03812; GOG-0262/ACRIN 6695; 11-00374; CDR0000681448; ACRIN 6695; GOG-0262; GOG-0262; U10CA180868; U10CA027469
• First Posted: Jul 22, 2010
• Last Update Posted: Jul 28, 2022
• Last Verified: Jun 1, 2022

• Additional relevant MeSH terms: Carcinoma; Adenocarcinoma; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Peritoneal Neoplasms; Carcinoma, Transitional Cell; Cystadenocarcinoma, Serous; Carcinoma, Endometrioid; Adenocarcinoma, Mucinous; Cystadenocarcinoma; Brenner Tumor; Paclitaxel; Bevacizumab; Carboplatin; Albumin-Bound Paclitaxel; Antineoplastic Agents, Immunological; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G

Study Results

Participant Flow

Recruitment Details	Newly diagnosed women with high-risk early stage or advanced stage epithelial ovarian cancer enrolled from September 27, 2010 to February 8, 2012.These women were randomly assigned to receive either carboplatin (AUC 6) combined with either paclitaxel 175 mg/m2 q 21 days or paclitaxel 80mg/m2 on days 1, 8 and 15. Bevacizumab was optional.
Pre-assignment Detail	112 additional women, whose treatment was not randomized, enrolled onto this study in order to evaluate whether findings from perfusion imaging are prognostic. This report focuses on the randomized treatment component of this study.

Arm/Group Title	Arm I (Adjuvant Chemotherapy Suboptimally Debulked)	Arm II (Neoadjuvant Chemotherapy)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Bevacizumab: Given IV Carboplatin: Given IV Computed Tomography: Correlative studies Paclitaxel: Given IV	Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Patients undergo interval cytoreductive surgery between courses 3 and 4. Bevacizumab: Given IV Carboplatin: Given IV Computed Tomography: Correlative studies Paclitaxel: Given IV Therapeutic Conventional Surgery: Undergo surgery
Period Title: Overall Study
STARTED	346	346
COMPLETED	346	346
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm I (Adjuvant Chemotherapy Suboptimally Debulked)	Arm II (Neoadjuvant Chemotherapy)	Total
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Bevacizumab: Given IV Carboplatin: Given IV Computed Tomography: Correlative studies Paclitaxel: Given IV Therapeutic Conventional Surgery: Undergo surgery	Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Patients undergo interval cytoreductive surgery between courses 3 and 4. Bevacizumab: Given IV Carboplatin: Given IV Computed Tomography: Correlative studies Paclitaxel: Given IV Therapeutic Conventional Surgery: Undergo surgery	Total of all reporting groups
Overall Participants	346	346	692
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	214 61.8%	217 62.7%	431 62.3%
>=65 years	132 38.2%	129 37.3%	261 37.7%
Sex: Female, Male (Count of Participants)
Female	346 100%	346 100%	692 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Canada	1 0.3%	0 0%	1 0.1%
United States	345 99.7%	345 99.7%	690 99.7%
South Korea	0 0%	1 0.3%	1 0.1%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival
Description	First progression or death for weekly paclitaxel treatment relative to standard 3 week paclitaxel. Progression is defined using response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	The timeframe is from enrollment onto the study up to 3 years following enrollment.

Outcome Measure Data

Analysis Population Description

Whole sample

Arm/Group Title	Arm I (Adjuvant Chemotherapy Suboptimally Debulked)	Arm II (Neoadjuvant Chemotherapy)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Bevacizumab: Given IV Carboplatin: Given IV Computed Tomography: Correlative studies Paclitaxel: Given IV	Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Patients undergo interval cytoreductive surgery between courses 3 and 4. Bevacizumab: Given IV Carboplatin: Given IV Computed Tomography: Correlative studies Paclitaxel: Given IV Therapeutic Conventional Surgery: Undergo surgery
Measure Participants	346	346
Median (95% Confidence Interval) [months]	14.7	14.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Adjuvant Chemotherapy Suboptimally Debulked), Arm II (Neoadjuvant Chemotherapy)
	Comments	Estimated hazard of first progression or death for weekly paclitaxel treatment relative to standard 3 week paclitaxel.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	.89
	Confidence Interval	(2-Sided) 95%; .74 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Median Duration of First Quartile Survival
Description	First Quartile Overall Survival
Time Frame	The timeframe is from enrollment onto the study up to 3 years after enrollment

Outcome Measure Data

Analysis Population Description

Whole sample

Arm/Group Title	Arm I (Adjuvant Chemotherapy Suboptimally Debulked)	Arm II (Neoadjuvant Chemotherapy)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Bevacizumab: Given IV Carboplatin: Given IV Computed Tomography: Correlative studies Paclitaxel: Given IV	Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Patients undergo interval cytoreductive surgery between courses 3 and 4. Bevacizumab: Given IV Carboplatin: Given IV Computed Tomography: Correlative studies Paclitaxel: Given IV Therapeutic Conventional Surgery: Undergo surgery
Measure Participants	346	346
Median (95% Confidence Interval) [months]	23.2	24

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Adjuvant Chemotherapy Suboptimally Debulked), Arm II (Neoadjuvant Chemotherapy)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	.94
	Confidence Interval	(2-Sided) 95%; .72 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Quality of Life Score as Measured by Functional Assessment of Cancer Therapy-Ovary-Total Outcome Index (Fact-O TOI)
Description	Mean quality of life score after 6 cycles of study treatment estimated from a mixed model. The FACT-O-TOI is composed of three subscales: Physical Well Being (PWB) (7 Items), Functional Well Being (FWB) (7 items), and Ovarian Cancer Subscale (OCS) (12 items). Each item in the FACT-O TOI are scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). A subscale score is computed as long as more than 50% of subscale items have been answered. A Total score of the FACT-O TOI is the summation of the three subscale scores; if more than 80% of the FACT-O TOI items provide valid responses and all three subscales have valid scores. A score of the FACT-O TOI is ranged 0-104 with a larger score indicating a more preferred state of health-related quality of life (HRQOL)
Time Frame	18 weeks after enrolling on the study, which is the time it takes to complete 6 cycles of treatment plus 3 weeks

Outcome Measure Data

Analysis Population Description

All individuals who did not opt for neo-adjuvant treatment and completed a baseline FACT-O TOI assessment and at least one follow-up assessment.

Arm/Group Title	Arm I (Adjuvant Chemotherapy Suboptimally Debulked)	Arm II (Neoadjuvant Chemotherapy)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Bevacizumab: Given IV Carboplatin: Given IV Computed Tomography: Correlative studies Paclitaxel: Given IV	Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Patients undergo interval cytoreductive surgery between courses 3 and 4. Bevacizumab: Given IV Carboplatin: Given IV Computed Tomography: Correlative studies Paclitaxel: Given IV Therapeutic Conventional Surgery: Undergo surgery
Measure Participants	292	287
Mean (Standard Error) [Units on a Scale]	70.9 (1.42)	68.2 (1.59)

4. Other Pre-specified Outcome

Title	Changes in the Tumor Perfusion Parameters as Quantified by Vascularity or Blood Volume; Perfusion or Blood Flow; Mean Transit Time; and Microvascular Permeability or Permeability Surface Area Product
Time Frame	Baseline (T0) up to 10 days after the start of course 2 (T2)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	AEs were assessed from the date of treatment initiation up to 30 days after the last cycle of treatment.
Arm/Group Title	Arm I (Adjuvant Chemotherapy Suboptimally Debulked)		Arm II (Neoadjuvant Chemotherapy)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Bevacizumab: Given IV Carboplatin: Given IV Computed Tomography: Correlative studies Paclitaxel: Given IV		Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses. Patients undergo interval cytoreductive surgery between courses 3 and 4. Bevacizumab: Given IV Carboplatin: Given IV Computed Tomography: Correlative studies Paclitaxel: Given IV Therapeutic Conventional Surgery: Undergo surgery
All Cause Mortality
	Arm I (Adjuvant Chemotherapy Suboptimally Debulked)		Arm II (Neoadjuvant Chemotherapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (Adjuvant Chemotherapy Suboptimally Debulked)		Arm II (Neoadjuvant Chemotherapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	122/346 (35.3%)		167/346 (48.3%)
Blood and lymphatic system disorders
Hemolytic Uremic Syndrome	0/346 (0%)		1/346 (0.3%)
Anemia	1/346 (0.3%)		1/346 (0.3%)
Febrile Neutropenia	10/346 (2.9%)		8/346 (2.3%)
Cardiac disorders
Atrial Fibrillation	1/346 (0.3%)		1/346 (0.3%)
Cardiac Arrest	1/346 (0.3%)		0/346 (0%)
Myocardial Infarction	1/346 (0.3%)		0/346 (0%)
Left Ventricular Systolic Dysfunction	1/346 (0.3%)		0/346 (0%)
Acute Coronary Syndrome	2/346 (0.6%)		0/346 (0%)
Ventricular Fibrillation	0/346 (0%)		1/346 (0.3%)
Ventricular Arrhythmia	1/346 (0.3%)		0/346 (0%)
Paroxysmal Atrial Tachycardia	0/346 (0%)		1/346 (0.3%)
Eye disorders
Dry Eye	1/346 (0.3%)		0/346 (0%)
Retinal Detachment	1/346 (0.3%)		0/346 (0%)
Gastrointestinal disorders
Colonic Obstruction	1/346 (0.3%)		1/346 (0.3%)
Colonic Perforation	0/346 (0%)		2/346 (0.6%)
Colonic Fistula	1/346 (0.3%)		1/346 (0.3%)
Colitis	3/346 (0.9%)		0/346 (0%)
Constipation	2/346 (0.6%)		1/346 (0.3%)
Diarrhea	4/346 (1.2%)		5/346 (1.4%)
Duodenal Perforation	0/346 (0%)		1/346 (0.3%)
Vomiting	5/346 (1.4%)		7/346 (2%)
Small Intestinal Obstruction	8/346 (2.3%)		13/346 (3.8%)
Abdominal Pain	6/346 (1.7%)		7/346 (2%)
Rectal Hemorrhage	0/346 (0%)		1/346 (0.3%)
Obstruction Gastric	1/346 (0.3%)		2/346 (0.6%)
Lower Gastrointestinal Hemorrhage	0/346 (0%)		1/346 (0.3%)
Gastrointestinal Disorders - Other	0/346 (0%)		2/346 (0.6%)
Ileal Perforation	1/346 (0.3%)		1/346 (0.3%)
Ileal Obstruction	1/346 (0.3%)		0/346 (0%)
Ileal Fistula	1/346 (0.3%)		0/346 (0%)
Retroperitoneal Hemorrhage	0/346 (0%)		1/346 (0.3%)
Gastric Hemorrhage	0/346 (0%)		1/346 (0.3%)
Nausea	0/346 (0%)		4/346 (1.2%)
Pancreatitis	0/346 (0%)		1/346 (0.3%)
Gastrointestinal Fistula	0/346 (0%)		1/346 (0.3%)
Gastric Ulcer	1/346 (0.3%)		0/346 (0%)
Rectal Pain	1/346 (0.3%)		0/346 (0%)
Gastric Perforation	0/346 (0%)		1/346 (0.3%)
Gastric Fistula	0/346 (0%)		1/346 (0.3%)
Esophageal Ulcer	1/346 (0.3%)		0/346 (0%)
Esophagitis	1/346 (0.3%)		0/346 (0%)
Jejunal Obstruction	0/346 (0%)		1/346 (0.3%)
General disorders
Pain	1/346 (0.3%)		1/346 (0.3%)
Multi-Organ Failure	1/346 (0.3%)		0/346 (0%)
Malaise	0/346 (0%)		1/346 (0.3%)
Non-Cardiac Chest Pain	1/346 (0.3%)		0/346 (0%)
Fatigue	0/346 (0%)		1/346 (0.3%)
Death Nos	1/346 (0.3%)		1/346 (0.3%)
Fever	1/346 (0.3%)		3/346 (0.9%)
Infusion Related Reaction	0/346 (0%)		2/346 (0.6%)
Hepatobiliary disorders
Portal Vein Thrombosis	1/346 (0.3%)		0/346 (0%)
Infections and infestations
Infections And Infestations - Other	0/346 (0%)		1/346 (0.3%)
Wound Infection	0/346 (0%)		1/346 (0.3%)
Tooth Infection	0/346 (0%)		1/346 (0.3%)
Splenic Infection	0/346 (0%)		1/346 (0.3%)
Skin Infection	1/346 (0.3%)		0/346 (0%)
Sepsis	4/346 (1.2%)		5/346 (1.4%)
Pleural Infection	1/346 (0.3%)		0/346 (0%)
Pelvic Infection	1/346 (0.3%)		3/346 (0.9%)
Lung Infection	0/346 (0%)		2/346 (0.6%)
Kidney Infection	0/346 (0%)		1/346 (0.3%)
Endocarditis Infective	0/346 (0%)		1/346 (0.3%)
Device Related Infection	0/346 (0%)		3/346 (0.9%)
Urinary Tract Infection	0/346 (0%)		2/346 (0.6%)
Catheter Related Infection	0/346 (0%)		5/346 (1.4%)
Enterocolitis Infectious	1/346 (0.3%)		0/346 (0%)
Bladder Infection	0/346 (0%)		1/346 (0.3%)
Anorectal Infection	0/346 (0%)		1/346 (0.3%)
Abdominal Infection	0/346 (0%)		1/346 (0.3%)
Injury, poisoning and procedural complications
Wound Dehiscence	0/346 (0%)		4/346 (1.2%)
Seroma	1/346 (0.3%)		0/346 (0%)
Stomal Ulcer	0/346 (0%)		1/346 (0.3%)
Hip Fracture	1/346 (0.3%)		0/346 (0%)
Fracture	0/346 (0%)		2/346 (0.6%)
Wound Complication	2/346 (0.6%)		0/346 (0%)
Investigations
Platelet Count Decreased	0/346 (0%)		2/346 (0.6%)
Neutrophil Count Decreased	7/346 (2%)		0/346 (0%)
Metabolism and nutrition disorders
Hyponatremia	0/346 (0%)		1/346 (0.3%)
Hypomagnesemia	1/346 (0.3%)		0/346 (0%)
Hypokalemia	2/346 (0.6%)		1/346 (0.3%)
Dehydration	4/346 (1.2%)		4/346 (1.2%)
Musculoskeletal and connective tissue disorders
Myalgia	0/346 (0%)		1/346 (0.3%)
Joint Effusion	1/346 (0.3%)		0/346 (0%)
Generalized Muscle Weakness	0/346 (0%)		1/346 (0.3%)
Chest Wall Pain	1/346 (0.3%)		0/346 (0%)
Bone Pain	1/346 (0.3%)		0/346 (0%)
Back Pain	0/346 (0%)		2/346 (0.6%)
Arthralgia	0/346 (0%)		1/346 (0.3%)
Abdominal Soft Tissue Necrosis	1/346 (0.3%)		0/346 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms Benign, Malignant And Unspecified (Incl	1/346 (0.3%)		0/346 (0%)
Tumor Pain	0/346 (0%)		1/346 (0.3%)
Nervous system disorders
Transient Ischemic Attacks	0/346 (0%)		1/346 (0.3%)
Stroke	2/346 (0.6%)		0/346 (0%)
Seizure	0/346 (0%)		1/346 (0.3%)
Peripheral Sensory Neuropathy	0/346 (0%)		2/346 (0.6%)
Peripheral Motor Neuropathy	0/346 (0%)		1/346 (0.3%)
Intracranial Hemorrhage	0/346 (0%)		1/346 (0.3%)
Headache	1/346 (0.3%)		0/346 (0%)
Syncope	1/346 (0.3%)		3/346 (0.9%)
Dizziness	0/346 (0%)		1/346 (0.3%)
Psychiatric disorders
Depression	0/346 (0%)		1/346 (0.3%)
Confusion	0/346 (0%)		2/346 (0.6%)
Anxiety	1/346 (0.3%)		0/346 (0%)
Renal and urinary disorders
Renal And Urinary Disorders - Other	1/346 (0.3%)		0/346 (0%)
Urinary Tract Obstruction	1/346 (0.3%)		0/346 (0%)
Urinary Fistula	0/346 (0%)		1/346 (0.3%)
Renal Calculi	1/346 (0.3%)		0/346 (0%)
Proteinuria	0/346 (0%)		1/346 (0.3%)
Acute Kidney Injury	1/346 (0.3%)		1/346 (0.3%)
Reproductive system and breast disorders
Vaginal Hemorrhage	0/346 (0%)		1/346 (0.3%)
Vaginal Fistula	0/346 (0%)		1/346 (0.3%)
Respiratory, thoracic and mediastinal disorders
Respiratory Failure	2/346 (0.6%)		0/346 (0%)
Pneumonitis	1/346 (0.3%)		0/346 (0%)
Pleural Effusion	3/346 (0.9%)		1/346 (0.3%)
Dyspnea	1/346 (0.3%)		4/346 (1.2%)
Skin and subcutaneous tissue disorders
Skin And Subcutaneous Tissue Disorders - Other	0/346 (0%)		1/346 (0.3%)
Skin Ulceration	0/346 (0%)		1/346 (0.3%)
Rash Maculo-Papular	0/346 (0%)		1/346 (0.3%)
Surgical and medical procedures
Surgical And Medical Procedures - Other	2/346 (0.6%)		1/346 (0.3%)
Vascular disorders
Thromboembolic Event	1/346 (0.3%)		9/346 (2.6%)
Peripheral Ischemia	0/346 (0%)		1/346 (0.3%)
Hypotension	3/346 (0.9%)		1/346 (0.3%)
Hypertension	5/346 (1.4%)		0/346 (0%)
Hematoma	0/346 (0%)		1/346 (0.3%)
Other (Not Including Serious) Adverse Events
	Arm I (Adjuvant Chemotherapy Suboptimally Debulked)		Arm II (Neoadjuvant Chemotherapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	343/346 (99.1%)		340/346 (98.3%)
Blood and lymphatic system disorders
Thrombotic Thrombocytopenic Purpura	3/346 (0.9%)		2/346 (0.6%)
Lymph Node Pain	1/346 (0.3%)		1/346 (0.3%)
Leukocytosis	1/346 (0.3%)		0/346 (0%)
Blood And Lymphatic System Disorders - Other	8/346 (2.3%)		13/346 (3.8%)
Anemia	324/346 (93.6%)		336/346 (97.1%)
Disseminated Intravascular Coagulation	1/346 (0.3%)		0/346 (0%)
Bone Marrow Hypocellular	1/346 (0.3%)		0/346 (0%)
Febrile Neutropenia	6/346 (1.7%)		6/346 (1.7%)
Cardiac disorders
Atrial Fibrillation	0/346 (0%)		6/346 (1.7%)
Ventricular Tachycardia	0/346 (0%)		1/346 (0.3%)
Supraventricular Tachycardia	0/346 (0%)		3/346 (0.9%)
Sinus Bradycardia	1/346 (0.3%)		2/346 (0.6%)
Palpitations	10/346 (2.9%)		24/346 (6.9%)
Left Ventricular Systolic Dysfunction	1/346 (0.3%)		1/346 (0.3%)
Acute Coronary Syndrome	1/346 (0.3%)		0/346 (0%)
Ventricular Fibrillation	0/346 (0%)		1/346 (0.3%)
Cardiac Disorders - Other	0/346 (0%)		1/346 (0.3%)
Pericardial Effusion	1/346 (0.3%)		1/346 (0.3%)
Ventricular Arrhythmia	0/346 (0%)		2/346 (0.6%)
Paroxysmal Atrial Tachycardia	2/346 (0.6%)		0/346 (0%)
Sinus Tachycardia	12/346 (3.5%)		17/346 (4.9%)
Chest Pain - Cardiac	5/346 (1.4%)		6/346 (1.7%)
Ear and labyrinth disorders
Middle Ear Inflammation	0/346 (0%)		2/346 (0.6%)
Vertigo	6/346 (1.7%)		10/346 (2.9%)
Tinnitus	28/346 (8.1%)		20/346 (5.8%)
Hearing Impaired	14/346 (4%)		13/346 (3.8%)
Ear Pain	8/346 (2.3%)		10/346 (2.9%)
External Ear Inflammation	0/346 (0%)		1/346 (0.3%)
Endocrine disorders
Adrenal Insufficiency	0/346 (0%)		1/346 (0.3%)
Hypothyroidism	0/346 (0%)		3/346 (0.9%)
Hyperthyroidism	1/346 (0.3%)		1/346 (0.3%)
Endocrine Disorders - Other	2/346 (0.6%)		1/346 (0.3%)
Cushingoid	0/346 (0%)		1/346 (0.3%)
Eye disorders
Eye Disorders - Other	10/346 (2.9%)		10/346 (2.9%)
Watering Eyes	11/346 (3.2%)		15/346 (4.3%)
Flashing Lights	3/346 (0.9%)		3/346 (0.9%)
Eye Pain	4/346 (1.2%)		1/346 (0.3%)
Glaucoma	1/346 (0.3%)		0/346 (0%)
Cataract	1/346 (0.3%)		2/346 (0.6%)
Photophobia	1/346 (0.3%)		0/346 (0%)
Conjunctivitis	2/346 (0.6%)		2/346 (0.6%)
Retinal Vascular Disorder	1/346 (0.3%)		0/346 (0%)
Blurred Vision	47/346 (13.6%)		51/346 (14.7%)
Dry Eye	3/346 (0.9%)		9/346 (2.6%)
Floaters	12/346 (3.5%)		11/346 (3.2%)
Vitreous Hemorrhage	0/346 (0%)		1/346 (0.3%)
Gastrointestinal disorders
Enterocolitis	1/346 (0.3%)		1/346 (0.3%)
Dysphagia	11/346 (3.2%)		14/346 (4%)
Dyspepsia	21/346 (6.1%)		28/346 (8.1%)
Dry Mouth	12/346 (3.5%)		10/346 (2.9%)
Colonic Obstruction	2/346 (0.6%)		0/346 (0%)
Colonic Perforation	2/346 (0.6%)		1/346 (0.3%)
Colonic Fistula	2/346 (0.6%)		2/346 (0.6%)
Colitis	6/346 (1.7%)		2/346 (0.6%)
Colonic Hemorrhage	0/346 (0%)		1/346 (0.3%)
Constipation	226/346 (65.3%)		214/346 (61.8%)
Diarrhea	146/346 (42.2%)		153/346 (44.2%)
Vomiting	133/346 (38.4%)		115/346 (33.2%)
Bloating	32/346 (9.2%)		21/346 (6.1%)
Stomach Pain	7/346 (2%)		3/346 (0.9%)
Salivary Duct Inflammation	0/346 (0%)		2/346 (0.6%)
Small Intestinal Obstruction	1/346 (0.3%)		2/346 (0.6%)
Anal Hemorrhage	3/346 (0.9%)		1/346 (0.3%)
Rectal Ulcer	0/346 (0%)		1/346 (0.3%)
Anal Mucositis	1/346 (0.3%)		0/346 (0%)
Rectal Fistula	0/346 (0%)		3/346 (0.9%)
Rectal Mucositis	0/346 (0%)		1/346 (0.3%)
Abdominal Pain	139/346 (40.2%)		138/346 (39.9%)
Proctitis	0/346 (0%)		1/346 (0.3%)
Periodontal Disease	3/346 (0.9%)		1/346 (0.3%)
Rectal Hemorrhage	16/346 (4.6%)		7/346 (2%)
Oral Dysesthesia	3/346 (0.9%)		3/346 (0.9%)
Mucositis Oral	76/346 (22%)		93/346 (26.9%)
Lower Gastrointestinal Hemorrhage	0/346 (0%)		2/346 (0.6%)
Gastrointestinal Disorders - Other	14/346 (4%)		16/346 (4.6%)
Anal Pain	0/346 (0%)		4/346 (1.2%)
Oral Hemorrhage	15/346 (4.3%)		8/346 (2.3%)
Ileus	5/346 (1.4%)		5/346 (1.4%)
Ileal Fistula	1/346 (0.3%)		0/346 (0%)
Anal Ulcer	0/346 (0%)		1/346 (0.3%)
Gastrointestinal Pain	5/346 (1.4%)		7/346 (2%)
Gastric Hemorrhage	1/346 (0.3%)		0/346 (0%)
Gingival Pain	7/346 (2%)		3/346 (0.9%)
Oral Pain	14/346 (4%)		16/346 (4.6%)
Abdominal Distension	25/346 (7.2%)		15/346 (4.3%)
Nausea	239/346 (69.1%)		215/346 (62.1%)
Pancreatitis	0/346 (0%)		1/346 (0.3%)
Gastroparesis	2/346 (0.6%)		3/346 (0.9%)
Gastrointestinal Fistula	0/346 (0%)		1/346 (0.3%)
Gastric Ulcer	1/346 (0.3%)		0/346 (0%)
Gastroesophageal Reflux Disease	21/346 (6.1%)		27/346 (7.8%)
Rectal Pain	1/346 (0.3%)		8/346 (2.3%)
Lip Pain	1/346 (0.3%)		0/346 (0%)
Gastric Fistula	0/346 (0%)		1/346 (0.3%)
Esophageal Ulcer	0/346 (0%)		1/346 (0.3%)
Esophagitis	2/346 (0.6%)		1/346 (0.3%)
Fecal Incontinence	0/346 (0%)		3/346 (0.9%)
Hemorrhoidal Hemorrhage	8/346 (2.3%)		10/346 (2.9%)
Hemorrhoids	14/346 (4%)		20/346 (5.8%)
Ascites	14/346 (4%)		4/346 (1.2%)
Toothache	11/346 (3.2%)		1/346 (0.3%)
Jejunal Obstruction	0/346 (0%)		1/346 (0.3%)
Anal Fistula	1/346 (0.3%)		0/346 (0%)
Esophageal Pain	0/346 (0%)		2/346 (0.6%)
Dental Caries	4/346 (1.2%)		2/346 (0.6%)
Flatulence	11/346 (3.2%)		10/346 (2.9%)
Gastritis	5/346 (1.4%)		5/346 (1.4%)
General disorders
General Disorders And Administration Site Conditio	3/346 (0.9%)		8/346 (2.3%)
Pain	93/346 (26.9%)		86/346 (24.9%)
Neck Edema	1/346 (0.3%)		1/346 (0.3%)
Malaise	8/346 (2.3%)		6/346 (1.7%)
Localized Edema	5/346 (1.4%)		4/346 (1.2%)
Irritability	1/346 (0.3%)		0/346 (0%)
Injection Site Reaction	0/346 (0%)		2/346 (0.6%)
Infusion Site Extravasation	0/346 (0%)		2/346 (0.6%)
Flu Like Symptoms	13/346 (3.8%)		8/346 (2.3%)
Edema Trunk	2/346 (0.6%)		3/346 (0.9%)
Non-Cardiac Chest Pain	14/346 (4%)		11/346 (3.2%)
Edema Limbs	54/346 (15.6%)		65/346 (18.8%)
Facial Pain	4/346 (1.2%)		4/346 (1.2%)
Edema Face	4/346 (1.2%)		3/346 (0.9%)
Fatigue	293/346 (84.7%)		300/346 (86.7%)
Fever	26/346 (7.5%)		38/346 (11%)
Gait Disturbance	5/346 (1.4%)		9/346 (2.6%)
Chills	14/346 (4%)		23/346 (6.6%)
Infusion Related Reaction	12/346 (3.5%)		15/346 (4.3%)
Hepatobiliary disorders
Hepatobiliary Disorders - Other	1/346 (0.3%)		0/346 (0%)
Hepatic Pain	1/346 (0.3%)		0/346 (0%)
Portal Vein Thrombosis	1/346 (0.3%)		0/346 (0%)
Cholecystitis	0/346 (0%)		1/346 (0.3%)
Immune system disorders
Allergic Reaction	18/346 (5.2%)		11/346 (3.2%)
Cytokine Release Syndrome	1/346 (0.3%)		0/346 (0%)
Immune System Disorders - Other	1/346 (0.3%)		1/346 (0.3%)
Infections and infestations
Infections And Infestations - Other	12/346 (3.5%)		11/346 (3.2%)
Wound Infection	9/346 (2.6%)		6/346 (1.7%)
Upper Respiratory Infection	19/346 (5.5%)		16/346 (4.6%)
Tooth Infection	8/346 (2.3%)		9/346 (2.6%)
Stoma Site Infection	0/346 (0%)		1/346 (0.3%)
Vulval Infection	3/346 (0.9%)		2/346 (0.6%)
Skin Infection	5/346 (1.4%)		17/346 (4.9%)
Sinusitis	15/346 (4.3%)		16/346 (4.6%)
Sepsis	1/346 (0.3%)		3/346 (0.9%)
Salivary Gland Infection	0/346 (0%)		1/346 (0.3%)
Rhinitis Infective	4/346 (1.2%)		1/346 (0.3%)
Rash Pustular	1/346 (0.3%)		0/346 (0%)
Pleural Infection	0/346 (0%)		1/346 (0.3%)
Pharyngitis	0/346 (0%)		2/346 (0.6%)
Peritoneal Infection	0/346 (0%)		1/346 (0.3%)
Peripheral Nerve Infection	1/346 (0.3%)		0/346 (0%)
Otitis Media	1/346 (0.3%)		0/346 (0%)
Papulopustular Rash	3/346 (0.9%)		3/346 (0.9%)
Otitis Externa	1/346 (0.3%)		1/346 (0.3%)
Nail Infection	4/346 (1.2%)		7/346 (2%)
Mucosal Infection	4/346 (1.2%)		4/346 (1.2%)
Pelvic Infection	1/346 (0.3%)		1/346 (0.3%)
Lung Infection	3/346 (0.9%)		3/346 (0.9%)
Laryngitis	1/346 (0.3%)		3/346 (0.9%)
Kidney Infection	1/346 (0.3%)		0/346 (0%)
Hepatitis Viral	1/346 (0.3%)		0/346 (0%)
Eye Infection	0/346 (0%)		2/346 (0.6%)
Esophageal Infection	1/346 (0.3%)		0/346 (0%)
Duodenal Infection	0/346 (0%)		1/346 (0.3%)
Device Related Infection	0/346 (0%)		2/346 (0.6%)
Conjunctivitis Infective	0/346 (0%)		1/346 (0.3%)
Gum Infection	2/346 (0.6%)		1/346 (0.3%)
Vaginal Infection	9/346 (2.6%)		5/346 (1.4%)
Urinary Tract Infection	44/346 (12.7%)		52/346 (15%)
Catheter Related Infection	1/346 (0.3%)		5/346 (1.4%)
Bronchial Infection	5/346 (1.4%)		3/346 (0.9%)
Enterocolitis Infectious	4/346 (1.2%)		3/346 (0.9%)
Bladder Infection	3/346 (0.9%)		8/346 (2.3%)
Lip Infection	1/346 (0.3%)		0/346 (0%)
Anorectal Infection	1/346 (0.3%)		1/346 (0.3%)
Abdominal Infection	1/346 (0.3%)		3/346 (0.9%)
Injury, poisoning and procedural complications
Injury, Poisoning And Procedural Complications - O	2/346 (0.6%)		1/346 (0.3%)
Wrist Fracture	3/346 (0.9%)		0/346 (0%)
Wound Dehiscence	5/346 (1.4%)		7/346 (2%)
Vascular Access Complication	1/346 (0.3%)		4/346 (1.2%)
Vaginal Anastomotic Leak	0/346 (0%)		2/346 (0.6%)
Spinal Fracture	1/346 (0.3%)		0/346 (0%)
Seroma	2/346 (0.6%)		3/346 (0.9%)
Tracheal Obstruction	0/346 (0%)		1/346 (0.3%)
Intestinal Stoma Site Bleeding	0/346 (0%)		1/346 (0.3%)
Stomal Ulcer	0/346 (0%)		1/346 (0.3%)
Fracture	1/346 (0.3%)		3/346 (0.9%)
Fall	8/346 (2.3%)		9/346 (2.6%)
Wound Complication	17/346 (4.9%)		13/346 (3.8%)
Intraoperative Musculoskeletal Injury	1/346 (0.3%)		0/346 (0%)
Burn	2/346 (0.6%)		2/346 (0.6%)
Bruising	20/346 (5.8%)		17/346 (4.9%)
Ankle Fracture	1/346 (0.3%)		0/346 (0%)
Investigations
Investigations - Other	15/346 (4.3%)		14/346 (4%)
Weight Loss	56/346 (16.2%)		48/346 (13.9%)
Weight Gain	53/346 (15.3%)		39/346 (11.3%)
Serum Amylase Increased	1/346 (0.3%)		0/346 (0%)
Platelet Count Decreased	257/346 (74.3%)		274/346 (79.2%)
Pancreatic Enzymes Decreased	0/346 (0%)		2/346 (0.6%)
Lymphocyte Count Decreased	18/346 (5.2%)		36/346 (10.4%)
Lipase Increased	1/346 (0.3%)		0/346 (0%)
Inr Increased	5/346 (1.4%)		9/346 (2.6%)
Hemoglobin Increased	1/346 (0.3%)		1/346 (0.3%)
Ggt Increased	2/346 (0.6%)		5/346 (1.4%)
Ejection Fraction Decreased	1/346 (0.3%)		0/346 (0%)
Creatinine Increased	24/346 (6.9%)		34/346 (9.8%)
Cholesterol High	6/346 (1.7%)		5/346 (1.4%)
Neutrophil Count Decreased	325/346 (93.9%)		331/346 (95.7%)
Urine Output Decreased	0/346 (0%)		1/346 (0.3%)
Cardiac Troponin I Increased	1/346 (0.3%)		0/346 (0%)
Cpk Increased	0/346 (0%)		1/346 (0.3%)
Blood Bilirubin Increased	7/346 (2%)		8/346 (2.3%)
White Blood Cell Decreased	321/346 (92.8%)		332/346 (96%)
Aspartate Aminotransferase Increased	40/346 (11.6%)		42/346 (12.1%)
Alkaline Phosphatase Increased	41/346 (11.8%)		47/346 (13.6%)
Alanine Aminotransferase Increased	38/346 (11%)		39/346 (11.3%)
Activated Partial Thromboplastin Time Prolonged	1/346 (0.3%)		6/346 (1.7%)
Metabolism and nutrition disorders
Metabolism And Nutrition Disorders - Other	11/346 (3.2%)		6/346 (1.7%)
Hypophosphatemia	10/346 (2.9%)		22/346 (6.4%)
Hyponatremia	57/346 (16.5%)		63/346 (18.2%)
Hypomagnesemia	68/346 (19.7%)		86/346 (24.9%)
Hypokalemia	60/346 (17.3%)		66/346 (19.1%)
Hypoglycemia	14/346 (4%)		15/346 (4.3%)
Hypocalcemia	28/346 (8.1%)		48/346 (13.9%)
Hypoalbuminemia	49/346 (14.2%)		65/346 (18.8%)
Hyperuricemia	2/346 (0.6%)		2/346 (0.6%)
Hypertriglyceridemia	2/346 (0.6%)		4/346 (1.2%)
Hypernatremia	9/346 (2.6%)		10/346 (2.9%)
Hypermagnesemia	4/346 (1.2%)		5/346 (1.4%)
Hyperkalemia	16/346 (4.6%)		15/346 (4.3%)
Hyperglycemia	73/346 (21.1%)		82/346 (23.7%)
Hypercalcemia	17/346 (4.9%)		13/346 (3.8%)
Glucose Intolerance	4/346 (1.2%)		1/346 (0.3%)
Dehydration	36/346 (10.4%)		38/346 (11%)
Anorexia	102/346 (29.5%)		116/346 (33.5%)
Acidosis	2/346 (0.6%)		0/346 (0%)
Musculoskeletal and connective tissue disorders
Superficial Soft Tissue Fibrosis	0/346 (0%)		1/346 (0.3%)
Pain In Extremity	80/346 (23.1%)		69/346 (19.9%)
Osteoporosis	1/346 (0.3%)		3/346 (0.9%)
Neck Pain	21/346 (6.1%)		15/346 (4.3%)
Myositis	2/346 (0.6%)		0/346 (0%)
Myalgia	91/346 (26.3%)		75/346 (21.7%)
Musculoskeletal Deformity	0/346 (0%)		1/346 (0.3%)
Muscle Weakness Upper Limb	4/346 (1.2%)		3/346 (0.9%)
Muscle Weakness Trunk	1/346 (0.3%)		2/346 (0.6%)
Muscle Weakness Lower Limb	15/346 (4.3%)		13/346 (3.8%)
Muscle Weakness Right-Sided	0/346 (0%)		2/346 (0.6%)
Muscle Weakness Left-Sided	0/346 (0%)		2/346 (0.6%)
Joint Range Of Motion Decreased Cervical Spine	1/346 (0.3%)		0/346 (0%)
Joint Range Of Motion Decreased	4/346 (1.2%)		7/346 (2%)
Joint Effusion	1/346 (0.3%)		3/346 (0.9%)
Generalized Muscle Weakness	35/346 (10.1%)		44/346 (12.7%)
Flank Pain	10/346 (2.9%)		3/346 (0.9%)
Chest Wall Pain	7/346 (2%)		14/346 (4%)
Trismus	1/346 (0.3%)		0/346 (0%)
Buttock Pain	1/346 (0.3%)		1/346 (0.3%)
Bone Pain	33/346 (9.5%)		25/346 (7.2%)
Back Pain	70/346 (20.2%)		54/346 (15.6%)
Arthritis	19/346 (5.5%)		18/346 (5.2%)
Arthralgia	119/346 (34.4%)		83/346 (24%)
Musculoskeletal And Connective Tissue Disorder -	4/346 (1.2%)		8/346 (2.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms Benign, Malignant And Unspecified (Including cysts and polyps	5/346 (1.4%)		3/346 (0.9%)
Tumor Pain	1/346 (0.3%)		1/346 (0.3%)
Nervous system disorders
Nervous System Disorders - Other	3/346 (0.9%)		6/346 (1.7%)
Tremor	4/346 (1.2%)		9/346 (2.6%)
Transient Ischemic Attacks	1/346 (0.3%)		1/346 (0.3%)
Somnolence	1/346 (0.3%)		1/346 (0.3%)
Reversible Posterior Leukoencephalopathy Syndrome	1/346 (0.3%)		0/346 (0%)
Presyncope	1/346 (0.3%)		3/346 (0.9%)
Peripheral Sensory Neuropathy	244/346 (70.5%)		233/346 (67.3%)
Peripheral Motor Neuropathy	19/346 (5.5%)		20/346 (5.8%)
Paresthesia	19/346 (5.5%)		24/346 (6.9%)
Nystagmus	0/346 (0%)		1/346 (0.3%)
Neuralgia	5/346 (1.4%)		6/346 (1.7%)
Memory Impairment	20/346 (5.8%)		20/346 (5.8%)
Lethargy	0/346 (0%)		1/346 (0.3%)
Movements Involuntary	5/346 (1.4%)		3/346 (0.9%)
Hypersomnia	1/346 (0.3%)		0/346 (0%)
Headache	116/346 (33.5%)		112/346 (32.4%)
Facial Nerve Disorder	0/346 (0%)		1/346 (0.3%)
Extrapyramidal Disorder	2/346 (0.6%)		0/346 (0%)
Radiculitis	0/346 (0%)		1/346 (0.3%)
Encephalopathy	1/346 (0.3%)		0/346 (0%)
Dysphasia	2/346 (0.6%)		2/346 (0.6%)
Dysgeusia	42/346 (12.1%)		58/346 (16.8%)
Sinus Pain	5/346 (1.4%)		6/346 (1.7%)
Dysesthesia	0/346 (0%)		2/346 (0.6%)
Dysarthria	1/346 (0.3%)		1/346 (0.3%)
Syncope	8/346 (2.3%)		6/346 (1.7%)
Dizziness	61/346 (17.6%)		66/346 (19.1%)
Concentration Impairment	1/346 (0.3%)		4/346 (1.2%)
Cognitive Disturbance	7/346 (2%)		5/346 (1.4%)
Ataxia	3/346 (0.9%)		4/346 (1.2%)
Amnesia	1/346 (0.3%)		1/346 (0.3%)
Akathisia	1/346 (0.3%)		1/346 (0.3%)
Psychiatric disorders
Psychiatric Disorders - Other	2/346 (0.6%)		1/346 (0.3%)
Suicidal Ideation	1/346 (0.3%)		0/346 (0%)
Psychosis	0/346 (0%)		1/346 (0.3%)
Restlessness	8/346 (2.3%)		6/346 (1.7%)
Libido Decreased	1/346 (0.3%)		1/346 (0.3%)
Insomnia	90/346 (26%)		85/346 (24.6%)
Depression	66/346 (19.1%)		66/346 (19.1%)
Delirium	0/346 (0%)		1/346 (0.3%)
Confusion	5/346 (1.4%)		5/346 (1.4%)
Anxiety	60/346 (17.3%)		68/346 (19.7%)
Agitation	4/346 (1.2%)		7/346 (2%)
Renal and urinary disorders
Renal And Urinary Disorders - Other	4/346 (1.2%)		12/346 (3.5%)
Urine Discoloration	0/346 (0%)		1/346 (0.3%)
Urinary Urgency	9/346 (2.6%)		11/346 (3.2%)
Urinary Tract Obstruction	2/346 (0.6%)		3/346 (0.9%)
Urinary Retention	4/346 (1.2%)		7/346 (2%)
Urinary Incontinence	13/346 (3.8%)		17/346 (4.9%)
Urinary Tract Pain	16/346 (4.6%)		18/346 (5.2%)
Urinary Frequency	14/346 (4%)		34/346 (9.8%)
Urinary Fistula	0/346 (0%)		1/346 (0.3%)
Renal Calculi	1/346 (0.3%)		1/346 (0.3%)
Proteinuria	47/346 (13.6%)		55/346 (15.9%)
Hematuria	11/346 (3.2%)		13/346 (3.8%)
Cystitis Noninfective	0/346 (0%)		3/346 (0.9%)
Chronic Kidney Disease	2/346 (0.6%)		6/346 (1.7%)
Bladder Spasm	3/346 (0.9%)		2/346 (0.6%)
Acute Kidney Injury	3/346 (0.9%)		2/346 (0.6%)
Reproductive system and breast disorders
Reproductive System And Breast Disorders - Other	3/346 (0.9%)		2/346 (0.6%)
Vaginal Pain	4/346 (1.2%)		7/346 (2%)
Vaginal Hemorrhage	4/346 (1.2%)		7/346 (2%)
Vaginal Fistula	1/346 (0.3%)		4/346 (1.2%)
Vaginal Dryness	8/346 (2.3%)		6/346 (1.7%)
Perineal Pain	0/346 (0%)		1/346 (0.3%)
Pelvic Pain	11/346 (3.2%)		8/346 (2.3%)
Menorrhagia	0/346 (0%)		1/346 (0.3%)
Vaginal Discharge	7/346 (2%)		17/346 (4.9%)
Vaginal Inflammation	1/346 (0.3%)		3/346 (0.9%)
Genital Edema	0/346 (0%)		2/346 (0.6%)
Dyspareunia	5/346 (1.4%)		4/346 (1.2%)
Breast Pain	1/346 (0.3%)		3/346 (0.9%)
Respiratory, thoracic and mediastinal disorders
Respiratory, Thoracic And Mediastinal Disorders -	5/346 (1.4%)		6/346 (1.7%)
Voice Alteration	15/346 (4.3%)		15/346 (4.3%)
Sore Throat	27/346 (7.8%)		25/346 (7.2%)
Sneezing	4/346 (1.2%)		2/346 (0.6%)
Sinus Disorder	10/346 (2.9%)		12/346 (3.5%)
Respiratory Failure	0/346 (0%)		1/346 (0.3%)
Pulmonary Hypertension	0/346 (0%)		2/346 (0.6%)
Postnasal Drip	22/346 (6.4%)		24/346 (6.9%)
Pneumothorax	1/346 (0.3%)		0/346 (0%)
Pneumonitis	1/346 (0.3%)		0/346 (0%)
Pleural Effusion	12/346 (3.5%)		9/346 (2.6%)
Pharyngolaryngeal Pain	3/346 (0.9%)		1/346 (0.3%)
Pharyngeal Mucositis	1/346 (0.3%)		2/346 (0.6%)
Pharyngeal Hemorrhage	1/346 (0.3%)		1/346 (0.3%)
Nasal Congestion	42/346 (12.1%)		45/346 (13%)
Pleuritic Pain	2/346 (0.6%)		3/346 (0.9%)
Productive Cough	3/346 (0.9%)		8/346 (2.3%)
Laryngeal Inflammation	2/346 (0.6%)		1/346 (0.3%)
Laryngeal Hemorrhage	0/346 (0%)		1/346 (0.3%)
Hoarseness	20/346 (5.8%)		25/346 (7.2%)
Sleep Apnea	0/346 (0%)		2/346 (0.6%)
Hiccups	0/346 (0%)		1/346 (0.3%)
Epistaxis	89/346 (25.7%)		131/346 (37.9%)
Dyspnea	120/346 (34.7%)		131/346 (37.9%)
Cough	76/346 (22%)		90/346 (26%)
Wheezing	3/346 (0.9%)		9/346 (2.6%)
Atelectasis	2/346 (0.6%)		3/346 (0.9%)
Aspiration	0/346 (0%)		1/346 (0.3%)
Allergic Rhinitis	39/346 (11.3%)		46/346 (13.3%)
Adult Respiratory Distress Syndrome	0/346 (0%)		1/346 (0.3%)
Skin and subcutaneous tissue disorders
Skin And Subcutaneous Tissue Disorders - Other	28/346 (8.1%)		33/346 (9.5%)
Urticaria	1/346 (0.3%)		2/346 (0.6%)
Skin Ulceration	10/346 (2.9%)		4/346 (1.2%)
Skin Induration	2/346 (0.6%)		3/346 (0.9%)
Skin Hyperpigmentation	7/346 (2%)		9/346 (2.6%)
Scalp Pain	5/346 (1.4%)		2/346 (0.6%)
Rash Acneiform	18/346 (5.2%)		24/346 (6.9%)
Purpura	1/346 (0.3%)		3/346 (0.9%)
Pruritus	24/346 (6.9%)		22/346 (6.4%)
Photosensitivity	1/346 (0.3%)		1/346 (0.3%)
Periorbital Edema	1/346 (0.3%)		0/346 (0%)
Palmar-Plantar Erythrodysesthesia Syndrome	1/346 (0.3%)		5/346 (1.4%)
Pain Of Skin	3/346 (0.9%)		7/346 (2%)
Rash Maculo-Papular	43/346 (12.4%)		74/346 (21.4%)
Skin Hypopigmentation	0/346 (0%)		2/346 (0.6%)
Nail Ridging	12/346 (3.5%)		9/346 (2.6%)
Nail Loss	6/346 (1.7%)		20/346 (5.8%)
Nail Discoloration	13/346 (3.8%)		33/346 (9.5%)
Hypertrichosis	1/346 (0.3%)		0/346 (0%)
Hyperhidrosis	8/346 (2.3%)		1/346 (0.3%)
Hirsutism	0/346 (0%)		1/346 (0.3%)
Erythroderma	0/346 (0%)		2/346 (0.6%)
Erythema Multiforme	5/346 (1.4%)		3/346 (0.9%)
Dry Skin	24/346 (6.9%)		36/346 (10.4%)
Bullous Dermatitis	0/346 (0%)		2/346 (0.6%)
Body Odor	1/346 (0.3%)		0/346 (0%)
Alopecia	258/346 (74.6%)		235/346 (67.9%)
Social circumstances
Social Circumstances - Other	6/346 (1.7%)		2/346 (0.6%)
Menopause	1/346 (0.3%)		0/346 (0%)
Surgical and medical procedures
Surgical And Medical Procedures - Other	8/346 (2.3%)		11/346 (3.2%)
Vascular disorders
Vascular Disorders - Other	1/346 (0.3%)		4/346 (1.2%)
Thromboembolic Event	23/346 (6.6%)		21/346 (6.1%)
Superficial Thrombophlebitis	1/346 (0.3%)		1/346 (0.3%)
Phlebitis	0/346 (0%)		1/346 (0.3%)
Peripheral Ischemia	1/346 (0.3%)		0/346 (0%)
Lymphocele	2/346 (0.6%)		2/346 (0.6%)
Lymphedema	8/346 (2.3%)		12/346 (3.5%)
Hypotension	13/346 (3.8%)		14/346 (4%)
Hypertension	136/346 (39.3%)		122/346 (35.3%)
Hot Flashes	44/346 (12.7%)		39/346 (11.3%)
Hematoma	4/346 (1.2%)		3/346 (0.9%)
Flushing	9/346 (2.6%)		9/346 (2.6%)

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.