Bevacizumab, Radiation Therapy, and Cisplatin in Treating Patients With Previously Untreated Locally Advanced Cervical Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00369122
• Collaborator: Radiation Therapy Oncology Group (Other)
• Enrollment: 60
• Locations: 106
• Arm: 1
• Actual Duration (Months): 124.2
• Patients Per Site: 0.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial is studying how well giving bevacizumab together with radiation therapy and cisplatin works in treating patients with previously untreated locally advanced cervical cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of cervical cancer by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with radiation therapy and cisplatin may kill more tumor cells.

Condition or Disease	Intervention/Treatment	Phase
Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Cervical Cancer AJCC v6 and v7; Stage IIA Cervical Cancer AJCC v7; Stage IIB Cervical Cancer AJCC v6 and v7; Stage III Cervical Cancer AJCC v6 and v7	Biological: Bevacizumab; Drug: Cisplatin; Radiation: External Beam Radiation Therapy; Radiation: Internal Radiation Therapy	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine treatment-related serious adverse-event rates and adverse-event rates within the first 90 days from treatment start in patients with previously untreated locally advanced carcinoma of the cervix treated with bevacizumab, cisplatin, and concurrent pelvic radiotherapy.

SECONDARY OBJECTIVES:

1. Evaluate treatment-related serious adverse events and adverse events at any time.

2. Evaluate disease-free survival (local, regional, or distant failure, or death due to any cause).

3. Evaluate overall survival (death due to any cause). IV. Implement the image-based brachytherapy guidelines proposed by the Transatlantic Image-Guided Brachytherapy Working Group.

4. Collect CT scan or MRI-based dosimetry of brachytherapy applications used during the course of treatment for later analysis of feasibility and consistency as well as dose/volume assessments of tumor control and complications.

OUTLINE: This is a multicenter study.

Patients undergo pelvic external-beam radiotherapy (EBRT) once daily, 5 days a week, for 5 weeks for a total of 45 Gy.

Some patients also undergo low-dose rate brachytherapy twice, 1-3 weeks apart, beginning >= 4 weeks after initiating EBRT or high-dose rate brachytherapy 5 times, >= 48 hours apart, beginning >= 2 weeks after initiating EBRT. EBRT and chemotherapy are halted on the day of high-dose rate brachytherapy. Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 35.

After completion of study treatment, patients are followed periodically.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A PHASE II STUDY OF BEVACIZUMAB IN COMBINATION WITH DEFINITIVE RADIOTHERAPY AND CISPLATIN CHEMOTHERAPY IN UNTREATED PATIENTS WITH LOCALLY ADVANCED CERVICAL CARCINOMA
• Actual Study Start Date: Aug 11, 2006
• Actual Primary Completion Date: Jun 4, 2010
• Actual Study Completion Date: Dec 15, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (radiation therapy, bevacizumab, cisplatin) Patients undergo pelvic EBRT once daily, 5 days a week, for 5 weeks for a total of 45 Gy. Some patients also undergo low-dose rate brachytherapy twice, 1-3 weeks apart, beginning >= 4 weeks after initiating EBRT or high-dose rate brachytherapy 5 times, >= 48 hours apart, beginning >= 2 weeks after initiating EBRT. EBRT and chemotherapy are halted on the day of high-dose rate brachytherapy. Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 35.

Biological: Bevacizumab; Given IV; Other Names: Anti-VEGF Anti-VEGF Humanized Monoclonal Antibody Anti-VEGF rhuMAb Avastin Bevacizumab Biosimilar BEVZ92 Bevacizumab Biosimilar BI 695502 Bevacizumab Biosimilar CBT 124 Bevacizumab Biosimilar FKB238 BEVACIZUMAB, LICENSE HOLDER UNSPECIFIED 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 Recombinant Humanized Anti-VEGF Monoclonal Antibody rhuMab-VEGF ; Drug: Cisplatin; Given IV; Other Names: Abiplatin Blastolem Briplatin CDDP Cis-diammine-dichloroplatinum Cis-diamminedichloridoplatinum Cis-diamminedichloro Platinum (II) Cis-diamminedichloroplatinum Cis-dichloroammine Platinum (II) Cis-platinous Diamine Dichloride Cis-platinum Cis-platinum II Cis-platinum II Diamine Dichloride Cismaplat Cisplatina Cisplatinum Cisplatyl Citoplatino Citosin Cysplatyna DDP Lederplatin Metaplatin Neoplatin Peyrone's Chloride Peyrone's Salt Placis Plastistil Platamine Platiblastin Platiblastin-S Platinex Platinol Platinol- AQ Platinol-AQ Platinol-AQ VHA Plus Platinoxan Platinum Platinum Diamminodichloride Platiran Platistin Platosin ; Radiation: External Beam Radiation Therapy; Undergo EBRT; Other Names: Definitive Radiation Therapy EBRT External Beam Radiotherapy External Beam RT external radiation External Radiation Therapy external-beam radiation ; Radiation: Internal Radiation Therapy; Undergo brachytherapy; Other Names: BRACHYTHERAPY internal radiation Internal Radiation Brachytherapy Radiation Brachytherapy

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Treatment-related Serious Adverse Events (SAEs) and Adverse Events (AEs) as Assessed by CTCAE v. 3.0 Criteria Within the First 90 Days From Treatment Start. [From start of treatment to 90 days.]

   Adverse events (AEs) graded using CTCAE v3.0. Grade (Gr) refers to the severity of the AE and assigns Gr 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: 1= Mild AE, 2= Moderate AE, 3= Severe AE, 4= Life-threatening or disabling AE, 5= Death related to AE. Treatment-related SAEs defined as Grade (Gr) >= 4 vaginal bleeding, Gr >=4 thrombotic event, Gr >=3 arterial event, gastrointestinal (GI) bleeding , or bowel/bladder perforation, and any Gr 5 treatment-related AE. Treatment-related AEs defined as all SAEs, Gr 3-4 nausea, vomiting, or diarrhea persisting for >2 weeks despite medical intervention, Gr 4 neutropenia or leukopenia persisting for >7 days, febrile neutropenia defined as a temperature >38.5 degree Celsius and granulocytes < 1000/mm3, Grade 3-4 hematologic toxicity with the exception of neutropenia and leukopenia, and Grade 3-4 GI, renal, cardiac, pulmonary, hepatic, or neurologic AEs.

Secondary Outcome Measures

1. Number of Subjects With Treatment-related SAEs and AEs as Assessed by CTCAE v. 3.0 Criteria at Any Time. [From start of treatment to last follow-up, up to 6.0 years. Analysis occurred after all patients had been on study for at least 2 years.]

   Adverse events (AEs) graded using CTCAE v3.0. Grade (Gr) refers to the severity of the AE and assigns Gr 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: 1= Mild AE, 2= Moderate AE, 3= Severe AE, 4= Life-threatening or disabling AE, 5= Death related to AE. Treatment-related SAEs defined as Gr >= 4 vaginal bleeding, Gr >=4 thrombotic event, Gr >=3 arterial event, gastrointestinal (GI) bleeding , or bowel/bladder perforation, and any Gr 5 treatment-related AE. Treatment-related AEs defined as all SAEs, Gr 3-4 nausea, vomiting, or diarrhea persisting for >2 weeks despite medical intervention, Gr 4 neutropenia or leukopenia persisting for >7 days, febrile neutropenia defined as a temperature >38.5 degree Celsius and granulocytes < 1000/mm3, Grade 3-4 hematologic toxicity with the exception of neutropenia and leukopenia, and Grade 3-4 GI, renal, cardiac, pulmonary, hepatic, or neurologic AEs.

2. Disease-free Survival (Three-year Rate Reported) [From registration to 3 years]

   Failure is defined as local, regional, or distant disease, or death due to any cause. Disease-free survival time is defined as time from registration to the date of failure and disease-free survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive and disease-free are censored at the date of last contact.

3. Overall Survival (Three-year Rate Reported) [From registration to 3 years]

   Overall survival time is defined as time from registration to the date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed squamous cell, adenocarcinoma, or adenosquamous cell carcinoma of the uterine cervix, meeting 1 of the following stage criteria:

• Stage IIB-IIIB lymph nodes

• Stage IB-IIA disease with biopsy-proven pelvic node metastases and/or tumor size

= 5 cm

• No positive para-aortic lymph nodes

• Zubrod performance status 0-2

• WBC >= 3,000/mm^3

• Absolute granulocyte count >= 1,500/mm^3

• Platelet count >= 100,000/mm^3

• INR < 1.5

• Total bilirubin =< 1.5 mg/dL

• Serum creatinine =< 1.5 mg/dL

• AST and ALT =< 2.5 times upper limit of normal (ULN)

• Serum calcium =< 1.3 times ULN

• Hemoglobin >= 10 g/dL (transfusion allowed)

• Urine protein:creatinine ratio ? 0.5 OR urine protein < 1,000 mg by 24-hour urine collection

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• None of the following illnesses or conditions:

• Medical illness preventing the use of full-dose chemotherapy

• Evidence of bleeding diathesis or coagulopathy

• Prior medical or psychiatric illness that would prevent informed consent or limit survival to < 6 months

• History of aneurysms, cerebrovascular accident, or arteriovenous malformations

• Active gastrointestinal (GI) ulcers, GI bleeding, or active inflammatory bowel disease

• Serious, nonhealing wound, ulcer, or current healing fracture

• History of any type of fistula or GI perforation

• Intra-abdominal abscess within the past 6 months

• No prior invasive malignancy (except nonmelanomatous skin cancer) unless disease free for >= 3 years

• No significant traumatic injury within the past 28 days

• No clinically significant cardiovascular disease, such as the following:

• Uncontrolled hypertension (blood pressure > 160/90 mm Hg on medication)

• Myocardial infarction within the past 12 months

• Unstable angina within the past 12 months

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

• Unstable symptomatic arrhythmia requiring medication (i.e., chronic atrial arrhythmia, atrial fibrillation, or paroxysmal supraventricular tachycardia)

• Arterial thromboembolic events, including transient ischemic attack or clinically significant peripheral artery disease, within the past 6 months

• Arterial thromboembolic events, including transient ischemic attack or clinically significant peripheral artery disease, within the past 6 months

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

• No known HIV

• No prior organ transplant

• No prior surgery for carcinoma of the cervix other than biopsy

• No prior surgical debulking of pelvic or para-aortic nodes

• No prior pelvic radiotherapy, including transvaginal irradiation to control bleeding

• No prior systemic chemotherapy

• No major surgical procedure or open biopsy within the past 28 days or anticipation of need for major surgical procedure during the course of the study

• No fine needle aspirations or core biopsies within the past 7 days

• No concurrent major surgical procedure

• No concurrent epoetin alfa or Hypericum perforatum (St. John's wort)

• No concurrent intensity-modulated radiotherapy

• No concurrent transvaginal irradiation to control bleeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
2	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
3	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
4	University of Colorado	Denver	Colorado	United States	80217-3364
5	Integrated Community Oncology Network-Florida Cancer Center Beaches	Jacksonville Beach	Florida	United States	32250
6	Baptist MD Anderson Cancer Center	Jacksonville	Florida	United States	32207
7	Integrated Community Oncology Network-Southside Cancer Center	Jacksonville	Florida	United States	32207
8	University of Florida Health Science Center - Jacksonville	Jacksonville	Florida	United States	32209
9	Baptist Medical Center South	Jacksonville	Florida	United States	32258
10	21st Century Oncology-Orange Park	Orange Park	Florida	United States	32073
11	UF Cancer Center at Orlando Health	Orlando	Florida	United States	32806
12	21st Century Oncology-Palatka	Palatka	Florida	United States	32177
13	Bay Medical Center	Panama City	Florida	United States	32401
14	Integrated Community Oncology Network-Flager Cancer Center	Saint Augustine	Florida	United States	32086
15	Grady Health System	Atlanta	Georgia	United States	30303
16	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia	United States	30322
17	Northwest Community Hospital	Arlington Heights	Illinois	United States	60005
18	Northwestern University	Chicago	Illinois	United States	60611
19	John H Stroger Jr Hospital of Cook County	Chicago	Illinois	United States	60612
20	Franciscan St. James Health-Olympia Fields Campus	Olympia Fields	Illinois	United States	60461
21	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61603
22	Saint Vincent Anderson Regional Hospital/Cancer Center	Anderson	Indiana	United States	46016
23	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana	United States	46107
24	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana	United States	46260
25	Reid Health	Richmond	Indiana	United States	47374
26	Providence Medical Center	Kansas City	Kansas	United States	66112
27	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
28	Menorah Medical Center	Overland Park	Kansas	United States	66209
29	Radiation Oncology Practice Corporation Southwest	Overland Park	Kansas	United States	66210
30	Saint Luke's South Hospital	Overland Park	Kansas	United States	66213
31	Shawnee Mission Medical Center-KCCC	Shawnee Mission	Kansas	United States	66204
32	Baptist Health Lexington	Lexington	Kentucky	United States	40503
33	Norton Suburban Hospital and Medical Campus	Louisville	Kentucky	United States	40207
34	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
35	Boston Medical Center	Boston	Massachusetts	United States	02118
36	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
37	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
38	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
39	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
40	Cape Radiation Oncology	Cape Girardeau	Missouri	United States	63703
41	Centerpoint Medical Center LLC	Independence	Missouri	United States	64057
42	Truman Medical Center	Kansas City	Missouri	United States	64108
43	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
44	Radiation Oncology Practice Corporation South	Kansas City	Missouri	United States	64114
45	Saint Joseph Health Center	Kansas City	Missouri	United States	64114
46	North Kansas City Hospital	Kansas City	Missouri	United States	64116
47	Research Medical Center	Kansas City	Missouri	United States	64132
48	Radiation Oncology Practice Corporation - North	Kansas City	Missouri	United States	64154
49	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
50	Liberty Radiation Oncology Center	Liberty	Missouri	United States	64068
51	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
52	CHI Health Good Samaritan	Kearney	Nebraska	United States	68847
53	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
54	Saint Barnabas Medical Center	Livingston	New Jersey	United States	07039
55	Monmouth Medical Center	Long Branch	New Jersey	United States	07740
56	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey	United States	08903
57	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
58	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
59	New York-Presbyterian/Brooklyn Methodist Hospital	Brooklyn	New York	United States	11215
60	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
61	Highland Hospital	Rochester	New York	United States	14620
62	University of Rochester	Rochester	New York	United States	14642
63	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
64	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio	United States	44304
65	Summa Barberton Hospital	Barberton	Ohio	United States	44203
66	Grandview Hospital	Dayton	Ohio	United States	45405
67	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
68	Miami Valley Hospital	Dayton	Ohio	United States	45409
69	Samaritan North Health Center	Dayton	Ohio	United States	45415
70	Veteran Affairs Medical Center	Dayton	Ohio	United States	45428
71	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
72	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
73	Kettering Medical Center	Kettering	Ohio	United States	45429
74	Cancer Care Center, Incorporated	Salem	Ohio	United States	44460
75	Upper Valley Medical Center	Troy	Ohio	United States	45373
76	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
77	Cancer Treatment Center	Wooster	Ohio	United States	44691
78	Wright-Patterson Medical Center	Wright-Patterson Air Force Base	Ohio	United States	45433-5529
79	Greene Memorial Hospital	Xenia	Ohio	United States	45385
80	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
81	Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301
82	Einstein Medical Center Philadelphia	Philadelphia	Pennsylvania	United States	19141
83	Reading Hospital	West Reading	Pennsylvania	United States	19611
84	Lankenau Medical Center	Wynnewood	Pennsylvania	United States	19096
85	Main Line Health NCORP	Wynnewood	Pennsylvania	United States	19096
86	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee	United States	37660
87	M D Anderson Cancer Center	Houston	Texas	United States	77030
88	American Fork Hospital / Huntsman Intermountain Cancer Center	American Fork	Utah	United States	84003
89	Sandra L Maxwell Cancer Center	Cedar City	Utah	United States	84720
90	Logan Regional Hospital	Logan	Utah	United States	84321
91	Cottonwood Hospital Medical Center	Murray	Utah	United States	84107
92	Intermountain Medical Center	Murray	Utah	United States	84107
93	McKay-Dee Hospital Center	Ogden	Utah	United States	84403
94	Utah Valley Regional Medical Center	Provo	Utah	United States	84604
95	Dixie Medical Center Regional Cancer Center	Saint George	Utah	United States	84770
96	Intermountain Health Care	Salt Lake City	Utah	United States	84103
97	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah	United States	84106
98	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
99	LDS Hospital	Salt Lake City	Utah	United States	84143
100	Southwest VA Regional Cancer Center	Norton	Virginia	United States	24273
101	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington	United States	98902
102	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
103	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
104	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
105	McGill University Department of Oncology	Montreal	Quebec	Canada	H2W 1S6
106	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T 7T1

Sponsors and Collaborators

• National Cancer Institute (NCI)
• Radiation Therapy Oncology Group

Investigators

• Principal Investigator: Tracey Schefter, Radiation Therapy Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00369122
• Other Study ID Numbers: NCI-2009-00722; NCI-2009-00722; CDR0000493005; RTOG 0417; RTOG-0417; U10CA021661; NCT01530633
• First Posted: Aug 29, 2006
• Last Update Posted: Mar 20, 2018
• Last Verified: Feb 1, 2018

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Uterine Cervical Neoplasms; Carcinoma, Adenosquamous; Bevacizumab; Antineoplastic Agents, Immunological; Cisplatin; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G

Study Results

Participant Flow

Arm/Group Title	Treatment (Radiation Therapy, Bevacizumab, Cisplatin)
Arm/Group Description	Patients undergo pelvic EBRT once daily, 5 days a week, for 5 weeks for a total of 45 Gy. Some patients also undergo low-dose rate brachytherapy twice, 1-3 weeks apart, beginning >= 4 weeks after initiating EBRT or high-dose rate brachytherapy 5 times, >= 48 hours apart, beginning >= 2 weeks after initiating EBRT. EBRT and chemotherapy are halted on the day of high-dose rate brachytherapy. Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 35.
Period Title: Overall Study
STARTED	60
COMPLETED	49
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	Treatment (Radiation Therapy, Bevacizumab, Cisplatin)
Arm/Group Description	Patients undergo pelvic EBRT once daily, 5 days a week, for 5 weeks for a total of 45 Gy. Some patients also undergo low-dose rate brachytherapy twice, 1-3 weeks apart, beginning >= 4 weeks after initiating EBRT or high-dose rate brachytherapy 5 times, >= 48 hours apart, beginning >= 2 weeks after initiating EBRT. EBRT and chemotherapy are halted on the day of high-dose rate brachytherapy. Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 35.
Overall Participants	60
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	45.5
Sex: Female, Male (Count of Participants)
Female	60 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Treatment-related Serious Adverse Events (SAEs) and Adverse Events (AEs) as Assessed by CTCAE v. 3.0 Criteria Within the First 90 Days From Treatment Start.
Description	Adverse events (AEs) graded using CTCAE v3.0. Grade (Gr) refers to the severity of the AE and assigns Gr 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: 1= Mild AE, 2= Moderate AE, 3= Severe AE, 4= Life-threatening or disabling AE, 5= Death related to AE. Treatment-related SAEs defined as Grade (Gr) >= 4 vaginal bleeding, Gr >=4 thrombotic event, Gr >=3 arterial event, gastrointestinal (GI) bleeding , or bowel/bladder perforation, and any Gr 5 treatment-related AE. Treatment-related AEs defined as all SAEs, Gr 3-4 nausea, vomiting, or diarrhea persisting for >2 weeks despite medical intervention, Gr 4 neutropenia or leukopenia persisting for >7 days, febrile neutropenia defined as a temperature >38.5 degree Celsius and granulocytes < 1000/mm3, Grade 3-4 hematologic toxicity with the exception of neutropenia and leukopenia, and Grade 3-4 GI, renal, cardiac, pulmonary, hepatic, or neurologic AEs.
Time Frame	From start of treatment to 90 days.

Outcome Measure Data

Analysis Population Description

Eligible patients who began study treatment.

Arm/Group Title	Treatment (Radiation Therapy, Bevacizumab, Cisplatin)
Arm/Group Description	Patients undergo pelvic EBRT once daily, 5 days a week, for 5 weeks for a total of 45 Gy. Some patients also undergo low-dose rate brachytherapy twice, 1-3 weeks apart, beginning >= 4 weeks after initiating EBRT or high-dose rate brachytherapy 5 times, >= 48 hours apart, beginning >= 2 weeks after initiating EBRT. EBRT and chemotherapy are halted on the day of high-dose rate brachytherapy. Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 35.
Measure Participants	49
Serious Adverse Events	0 0%
Adverse Events	15 25%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment (Radiation Therapy, Bevacizumab, Cisplatin)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		Based on a report by Laciano, et al. an SAE rate of 5% and AE rate of 35% were considered tolerable and an SAE rate >=20% and AE rate >=55% excessive. If there were >=6 pts with SAES or >=22 pts with AEs then the treatment would be rejected. This study design provides alpha of 0.05 and power of 90%.

2. Secondary Outcome

Title	Number of Subjects With Treatment-related SAEs and AEs as Assessed by CTCAE v. 3.0 Criteria at Any Time.
Description	Adverse events (AEs) graded using CTCAE v3.0. Grade (Gr) refers to the severity of the AE and assigns Gr 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: 1= Mild AE, 2= Moderate AE, 3= Severe AE, 4= Life-threatening or disabling AE, 5= Death related to AE. Treatment-related SAEs defined as Gr >= 4 vaginal bleeding, Gr >=4 thrombotic event, Gr >=3 arterial event, gastrointestinal (GI) bleeding , or bowel/bladder perforation, and any Gr 5 treatment-related AE. Treatment-related AEs defined as all SAEs, Gr 3-4 nausea, vomiting, or diarrhea persisting for >2 weeks despite medical intervention, Gr 4 neutropenia or leukopenia persisting for >7 days, febrile neutropenia defined as a temperature >38.5 degree Celsius and granulocytes < 1000/mm3, Grade 3-4 hematologic toxicity with the exception of neutropenia and leukopenia, and Grade 3-4 GI, renal, cardiac, pulmonary, hepatic, or neurologic AEs.
Time Frame	From start of treatment to last follow-up, up to 6.0 years. Analysis occurred after all patients had been on study for at least 2 years.

Outcome Measure Data

Analysis Population Description

Eligible patients who started study treatment

Arm/Group Title	Treatment (Radiation Therapy, Bevacizumab, Cisplatin)
Arm/Group Description	Patients undergo pelvic EBRT once daily, 5 days a week, for 5 weeks for a total of 45 Gy. Some patients also undergo low-dose rate brachytherapy twice, 1-3 weeks apart, beginning >= 4 weeks after initiating EBRT or high-dose rate brachytherapy 5 times, >= 48 hours apart, beginning >= 2 weeks after initiating EBRT. EBRT and chemotherapy are halted on the day of high-dose rate brachytherapy. Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 35.
Measure Participants	49
Serious Adverse Events	0 0%
Adverse Events	18 30%

3. Secondary Outcome

Title	Disease-free Survival (Three-year Rate Reported)
Description	Failure is defined as local, regional, or distant disease, or death due to any cause. Disease-free survival time is defined as time from registration to the date of failure and disease-free survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive and disease-free are censored at the date of last contact.
Time Frame	From registration to 3 years

Outcome Measure Data

Analysis Population Description

Eligible patients who started study treatment

Arm/Group Title	Treatment (Radiation Therapy, Bevacizumab, Cisplatin)
Arm/Group Description	Patients undergo pelvic EBRT once daily, 5 days a week, for 5 weeks for a total of 45 Gy. Some patients also undergo low-dose rate brachytherapy twice, 1-3 weeks apart, beginning >= 4 weeks after initiating EBRT or high-dose rate brachytherapy 5 times, >= 48 hours apart, beginning >= 2 weeks after initiating EBRT. EBRT and chemotherapy are halted on the day of high-dose rate brachytherapy. Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 35.
Measure Participants	49
Number (95% Confidence Interval) [percentage of participants]	68.7 114.5%

4. Secondary Outcome

Title	Overall Survival (Three-year Rate Reported)
Description	Overall survival time is defined as time from registration to the date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.
Time Frame	From registration to 3 years

Outcome Measure Data

Analysis Population Description

Eligible patients who started study treatment

Arm/Group Title	Treatment (Radiation Therapy, Bevacizumab, Cisplatin)
Arm/Group Description	Patients undergo pelvic EBRT once daily, 5 days a week, for 5 weeks for a total of 45 Gy. Some patients also undergo low-dose rate brachytherapy twice, 1-3 weeks apart, beginning >= 4 weeks after initiating EBRT or high-dose rate brachytherapy 5 times, >= 48 hours apart, beginning >= 2 weeks after initiating EBRT. EBRT and chemotherapy are halted on the day of high-dose rate brachytherapy. Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 35.
Measure Participants	49
Number (95% Confidence Interval) [percentage of participants]	81.3 135.5%

Adverse Events

Adverse Event Reporting Description	Per the protocol, toxicity data was collected via Common Terminology Criteria (CTC) 3.0 then mapped to CTCAE 4.0 for reporting on this website. Subjects experiencing more than one of a given AE are counted only once for that AE.
Arm/Group Title	Treatment (Radiation Therapy, Bevacizumab, Cisplatin)
Arm/Group Description	Patients undergo pelvic EBRT once daily, 5 days a week, for 5 weeks for a total of 45 Gy. Some patients also undergo low-dose rate brachytherapy twice, 1-3 weeks apart, beginning >= 4 weeks after initiating EBRT or high-dose rate brachytherapy 5 times, >= 48 hours apart, beginning >= 2 weeks after initiating EBRT. EBRT and chemotherapy are halted on the day of high-dose rate brachytherapy. Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 35. Data is reported for all patients who received study treatment, which is 59 patients.
All Cause Mortality
	Treatment (Radiation Therapy, Bevacizumab, Cisplatin)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Radiation Therapy, Bevacizumab, Cisplatin)
	Affected / at Risk (%)	# Events
Total	13/59 (22%)
Blood and lymphatic system disorders
Febrile neutropenia	1/59 (1.7%)
Gastrointestinal disorders
Abdominal pain	1/59 (1.7%)
Diarrhea	2/59 (3.4%)
Nausea	1/59 (1.7%)
Proctitis	1/59 (1.7%)
Rectal pain	1/59 (1.7%)
Vomiting	1/59 (1.7%)
General disorders
Fever	1/59 (1.7%)
Immune system disorders
Allergic reaction	1/59 (1.7%)
Infections and infestations
Bladder infection	1/59 (1.7%)
Catheter related infection	1/59 (1.7%)
Lung infection	1/59 (1.7%)
Injury, poisoning and procedural complications
Vascular access complication	1/59 (1.7%)
Investigations
GGT increased	1/59 (1.7%)
Lymphocyte count decreased	2/59 (3.4%)
Neutrophil count decreased	1/59 (1.7%)
Platelet count decreased	2/59 (3.4%)
White blood cell decreased	1/59 (1.7%)
Metabolism and nutrition disorders
Anorexia	1/59 (1.7%)
Dehydration	3/59 (5.1%)
Hyperglycemia	1/59 (1.7%)
Hypokalemia	1/59 (1.7%)
Musculoskeletal and connective tissue disorders
Back pain	1/59 (1.7%)
Nervous system disorders
Syncope	1/59 (1.7%)
Psychiatric disorders
Depression	1/59 (1.7%)
Renal and urinary disorders
Urinary tract obstruction	1/59 (1.7%)
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage	1/59 (1.7%)
Vascular disorders
Thromboembolic event	1/59 (1.7%)
Other (Not Including Serious) Adverse Events
	Treatment (Radiation Therapy, Bevacizumab, Cisplatin)
	Affected / at Risk (%)	# Events
Total	59/59 (100%)
Blood and lymphatic system disorders
Anemia	32/59 (54.2%)
Ear and labyrinth disorders
Hearing impaired	1/59 (1.7%)
Tinnitus	4/59 (6.8%)
Eye disorders
Blurred vision	1/59 (1.7%)
Extraocular muscle paresis	1/59 (1.7%)
Flashing lights	1/59 (1.7%)
Gastrointestinal disorders
Abdominal distension	1/59 (1.7%)
Abdominal pain	11/59 (18.6%)
Anal fistula	1/59 (1.7%)
Anal pain	1/59 (1.7%)
Colitis	1/59 (1.7%)
Constipation	17/59 (28.8%)
Diarrhea	30/59 (50.8%)
Dry mouth	1/59 (1.7%)
Dyspepsia	4/59 (6.8%)
Dysphagia	2/59 (3.4%)
Esophagitis	1/59 (1.7%)
Gastritis	1/59 (1.7%)
Gastrointestinal disorders - Other	2/59 (3.4%)
Hemorrhoids	3/59 (5.1%)
Mucositis oral	2/59 (3.4%)
Nausea	32/59 (54.2%)
Proctitis	4/59 (6.8%)
Rectal hemorrhage	5/59 (8.5%)
Rectal pain	5/59 (8.5%)
Vomiting	15/59 (25.4%)
General disorders
Chills	4/59 (6.8%)
Edema limbs	4/59 (6.8%)
Fatigue	34/59 (57.6%)
Fever	4/59 (6.8%)
General disorders and administration site conditions - Other	1/59 (1.7%)
Non-cardiac chest pain	1/59 (1.7%)
Pain	4/59 (6.8%)
Infections and infestations
Infections and infestations - Other	4/59 (6.8%)
Sinusitis	1/59 (1.7%)
Soft tissue infection	1/59 (1.7%)
Urinary tract infection	3/59 (5.1%)
Vaginal infection	3/59 (5.1%)
Injury, poisoning and procedural complications
Dermatitis radiation	6/59 (10.2%)
Ureteric anastomotic leak	1/59 (1.7%)
Investigations
Activated partial thromboplastin time prolonged	2/59 (3.4%)
Alanine aminotransferase increased	8/59 (13.6%)
Alkaline phosphatase increased	5/59 (8.5%)
Aspartate aminotransferase increased	5/59 (8.5%)
Blood bilirubin increased	1/59 (1.7%)
Cholesterol high	1/59 (1.7%)
Creatinine increased	5/59 (8.5%)
Investigations - Other	3/59 (5.1%)
Lymphocyte count decreased	17/59 (28.8%)
Neutrophil count decreased	17/59 (28.8%)
Platelet count decreased	26/59 (44.1%)
Weight gain	3/59 (5.1%)
Weight loss	8/59 (13.6%)
White blood cell decreased	41/59 (69.5%)
Metabolism and nutrition disorders
Acidosis	2/59 (3.4%)
Anorexia	11/59 (18.6%)
Dehydration	2/59 (3.4%)
Hypercalcemia	7/59 (11.9%)
Hyperglycemia	17/59 (28.8%)
Hyperkalemia	2/59 (3.4%)
Hypernatremia	1/59 (1.7%)
Hyperuricemia	2/59 (3.4%)
Hypoalbuminemia	13/59 (22%)
Hypocalcemia	11/59 (18.6%)
Hypoglycemia	2/59 (3.4%)
Hypokalemia	17/59 (28.8%)
Hypomagnesemia	23/59 (39%)
Hyponatremia	16/59 (27.1%)
Hypophosphatemia	2/59 (3.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/59 (8.5%)
Back pain	6/59 (10.2%)
Bone pain	1/59 (1.7%)
Joint range of motion decreased	1/59 (1.7%)
Musculoskeletal and connective tissue disorder - Other	1/59 (1.7%)
Myalgia	2/59 (3.4%)
Neck pain	1/59 (1.7%)
Pain in extremity	1/59 (1.7%)
Nervous system disorders
Dizziness	5/59 (8.5%)
Dysgeusia	5/59 (8.5%)
Facial nerve disorder	1/59 (1.7%)
Headache	12/59 (20.3%)
Nervous system disorders - Other	3/59 (5.1%)
Peripheral motor neuropathy	1/59 (1.7%)
Peripheral sensory neuropathy	5/59 (8.5%)
Psychiatric disorders
Agitation	1/59 (1.7%)
Anxiety	8/59 (13.6%)
Depression	8/59 (13.6%)
Insomnia	8/59 (13.6%)
Renal and urinary disorders
Bladder spasm	1/59 (1.7%)
Chronic kidney disease	1/59 (1.7%)
Cystitis noninfective	5/59 (8.5%)
Hemoglobinuria	2/59 (3.4%)
Proteinuria	1/59 (1.7%)
Renal and urinary disorders - Other	3/59 (5.1%)
Urinary frequency	8/59 (13.6%)
Urinary incontinence	3/59 (5.1%)
Urinary retention	1/59 (1.7%)
Urinary tract obstruction	1/59 (1.7%)
Urinary tract pain	4/59 (6.8%)
Reproductive system and breast disorders
Irregular menstruation	4/59 (6.8%)
Lactation disorder	1/59 (1.7%)
Pelvic pain	11/59 (18.6%)
Perineal pain	3/59 (5.1%)
Reproductive system and breast disorders - Other	1/59 (1.7%)
Uterine hemorrhage	1/59 (1.7%)
Uterine obstruction	1/59 (1.7%)
Uterine pain	2/59 (3.4%)
Vaginal discharge	11/59 (18.6%)
Vaginal dryness	1/59 (1.7%)
Vaginal fistula	1/59 (1.7%)
Vaginal hemorrhage	25/59 (42.4%)
Vaginal inflammation	5/59 (8.5%)
Vaginal obstruction	6/59 (10.2%)
Vaginal pain	4/59 (6.8%)
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage	1/59 (1.7%)
Cough	3/59 (5.1%)
Dyspnea	5/59 (8.5%)
Epistaxis	3/59 (5.1%)
Voice alteration	5/59 (8.5%)
Skin and subcutaneous tissue disorders
Alopecia	2/59 (3.4%)
Dry skin	2/59 (3.4%)
Hyperhidrosis	2/59 (3.4%)
Pruritus	2/59 (3.4%)
Rash acneiform	1/59 (1.7%)
Rash maculo-papular	5/59 (8.5%)
Skin and subcutaneous tissue disorders - Other	2/59 (3.4%)
Skin hypopigmentation	1/59 (1.7%)
Skin induration	2/59 (3.4%)
Skin ulceration	1/59 (1.7%)
Telangiectasia	2/59 (3.4%)
Vascular disorders
Flushing	1/59 (1.7%)
Hot flashes	14/59 (23.7%)
Hypertension	6/59 (10.2%)
Hypotension	5/59 (8.5%)
Vascular disorders - Other	2/59 (3.4%)

Limitations/Caveats

Ineligible patients are included in the adverse event reporting on ClinicalTrials.gov, but not in endpoint results, nor in any publications, per the protocol.

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.