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

Cervical Adenocarcinoma Clinical Trial

Official title:

A PHASE II STUDY OF BEVACIZUMAB IN COMBINATION WITH DEFINITIVE RADIOTHERAPY AND CISPLATIN CHEMOTHERAPY IN UNTREATED PATIENTS WITH LOCALLY ADVANCED CERVICAL CARCINOMA

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00369122
• Other study ID #: NCI-2009-00722
• Secondary ID: NCI-2009-00722CD
• Status: Completed
• Phase: Phase 2
• First received: August 24, 2006
• Last updated: February 21, 2018
• Start date: August 11, 2006
• Est. completion date: December 15, 2016

Study information

• Verified date: February 2018
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

PRIMARY OBJECTIVES:

I. 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:

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

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

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

V. 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.

Other known NCT identifiers

• NCT01530633

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 15, 2016
• Est. primary completion date: June 4, 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Carcinoma, Adenosquamous
• Carcinoma, Squamous Cell
• 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
• Uterine Cervical Neoplasms

Intervention

Biological:
• Bevacizumab
Given IV

Drug:
• Cisplatin
Given IV

Radiation:
• External Beam Radiation Therapy
Undergo EBRT
• Internal Radiation Therapy
Undergo brachytherapy

Locations

Country	Name	City	State
Canada	London Regional Cancer Program	London	Ontario
Canada	McGill University Department of Oncology	Montreal	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
United States	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio
United States	American Fork Hospital / Huntsman Intermountain Cancer Center	American Fork	Utah
United States	Saint Vincent Anderson Regional Hospital/Cancer Center	Anderson	Indiana
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Northwest Community Hospital	Arlington Heights	Illinois
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Grady Health System	Atlanta	Georgia
United States	Summa Barberton Hospital	Barberton	Ohio
United States	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana
United States	Boston Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	New York-Presbyterian/Brooklyn Methodist Hospital	Brooklyn	New York
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Cape Radiation Oncology	Cape Girardeau	Missouri
United States	Sandra L Maxwell Cancer Center	Cedar City	Utah
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Health Center	Dayton	Ohio
United States	Veteran Affairs Medical Center	Dayton	Ohio
United States	University of Colorado	Denver	Colorado
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	M D Anderson Cancer Center	Houston	Texas
United States	Centerpoint Medical Center LLC	Independence	Missouri
United States	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	Baptist Medical Center South	Jacksonville	Florida
United States	Integrated Community Oncology Network-Southside Cancer Center	Jacksonville	Florida
United States	University of Florida Health Science Center - Jacksonville	Jacksonville	Florida
United States	Integrated Community Oncology Network-Florida Cancer Center Beaches	Jacksonville Beach	Florida
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Providence Medical Center	Kansas City	Kansas
United States	Radiation Oncology Practice Corporation - North	Kansas City	Missouri
United States	Radiation Oncology Practice Corporation South	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Joseph Health Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Truman Medical Center	Kansas City	Missouri
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Kettering Medical Center	Kettering	Ohio
United States	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Baptist Health Lexington	Lexington	Kentucky
United States	Liberty Radiation Oncology Center	Liberty	Missouri
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Logan Regional Hospital	Logan	Utah
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Norton Suburban Hospital and Medical Campus	Louisville	Kentucky
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Cottonwood Hospital Medical Center	Murray	Utah
United States	Intermountain Medical Center	Murray	Utah
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Southwest VA Regional Cancer Center	Norton	Virginia
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	Franciscan St. James Health-Olympia Fields Campus	Olympia Fields	Illinois
United States	21st Century Oncology-Orange Park	Orange Park	Florida
United States	UF Cancer Center at Orlando Health	Orlando	Florida
United States	Menorah Medical Center	Overland Park	Kansas
United States	Radiation Oncology Practice Corporation Southwest	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	21st Century Oncology-Palatka	Palatka	Florida
United States	Bay Medical Center	Panama City	Florida
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Einstein Medical Center Philadelphia	Philadelphia	Pennsylvania
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	Reid Health	Richmond	Indiana
United States	Highland Hospital	Rochester	New York
United States	University of Rochester	Rochester	New York
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Integrated Community Oncology Network-Flager Cancer Center	Saint Augustine	Florida
United States	Dixie Medical Center Regional Cancer Center	Saint George	Utah
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Cancer Care Center, Incorporated	Salem	Ohio
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Intermountain Health Care	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah
United States	Shawnee Mission Medical Center-KCCC	Shawnee Mission	Kansas
United States	Upper Valley Medical Center	Troy	Ohio
United States	Reading Hospital	West Reading	Pennsylvania
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Cancer Treatment Center	Wooster	Ohio
United States	Wright-Patterson Medical Center	Wright-Patterson Air Force Base	Ohio
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	Main Line Health NCORP	Wynnewood	Pennsylvania
United States	Greene Memorial Hospital	Xenia	Ohio
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	Radiation Therapy Oncology Group

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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.	From start of treatment to 90 days.
Secondary	Number of Subjects With Treatment-related SAEs and AEs as Assessed by CTCAE v. 3.0 Criteria at Any Time.	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.	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.
Secondary	Disease-free Survival (Three-year Rate Reported)	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.	From registration to 3 years
Secondary	Overall Survival (Three-year Rate Reported)	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.	From registration to 3 years