Clinical trial NCT00369122: Bevacizumab, Radiation Therapy, and Cisplatin in Treating Patients With Previously Untreated Locally Advanced Cervical Cancer
Official title: A PHASE II STUDY OF BEVACIZUMAB IN COMBINATION WITH DEFINITIVE RADIOTHERAPY AND CISPLATIN CHEMOTHERAPY IN UNTREATED PATIENTS WITH LOCALLY ADVANCED CERVICAL CARCINOMA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: Radiation Therapy Oncology Group
First posted: 2006-08-29
Enrollment: 60
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: From start of treatment to 90 days.
Secondary outcomes:
measure: Number of Subjects With Treatment-related SAEs and AEs as Assessed by CTCAE v. 3.0 Criteria at Any Time.
timeFrame: 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.
measure: Disease-free Survival (Three-year Rate Reported)
timeFrame: From registration to 3 years
measure: Overall Survival (Three-year Rate Reported)
timeFrame: From registration to 3 years
Other outcomes:
Locations:
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center/Disney Family Cancer Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: Colorado Springs
country: United States
facility: Penrose-Saint Francis Healthcare
state: Colorado
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Jacksonville Beach
country: United States
facility: Integrated Community Oncology Network-Florida Cancer Center Beaches
state: Florida
city: Jacksonville
country: United States
facility: Baptist MD Anderson Cancer Center
state: Florida
city: Jacksonville
country: United States
facility: Integrated Community Oncology Network-Southside Cancer Center
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Health Science Center - Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Baptist Medical Center South
state: Florida
city: Orange Park
country: United States
facility: 21st Century Oncology-Orange Park
state: Florida
city: Orlando
country: United States
facility: UF Cancer Center at Orlando Health
state: Florida
city: Palatka
country: United States
facility: 21st Century Oncology-Palatka
state: Florida
city: Panama City
country: United States
facility: Bay Medical Center
state: Florida
city: Saint Augustine
country: United States
facility: Integrated Community Oncology Network-Flager Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Grady Health System
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Arlington Heights
country: United States
facility: Northwest Community Hospital
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: John H Stroger Jr Hospital of Cook County
state: Illinois
city: Olympia Fields
country: United States
facility: Franciscan St. James Health-Olympia Fields Campus
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Anderson
country: United States
facility: Saint Vincent Anderson Regional Hospital/Cancer Center
state: Indiana
city: Beech Grove
country: United States
facility: Franciscan Saint Francis Health-Beech Grove
state: Indiana
city: Indianapolis
country: United States
facility: Saint Vincent Hospital and Health Care Center
state: Indiana
city: Richmond
country: United States
facility: Reid Health
state: Indiana
city: Kansas City
country: United States
facility: Providence Medical Center
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Overland Park
country: United States
facility: Menorah Medical Center
state: Kansas
city: Overland Park
country: United States
facility: Radiation Oncology Practice Corporation Southwest
state: Kansas
city: Overland Park
country: United States
facility: Saint Luke's South Hospital
state: Kansas
city: Shawnee Mission
country: United States
facility: Shawnee Mission Medical Center-KCCC
state: Kansas
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Louisville
country: United States
facility: Norton Suburban Hospital and Medical Campus
state: Kentucky
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Cape Girardeau
country: United States
facility: Cape Radiation Oncology
state: Missouri
city: Independence
country: United States
facility: Centerpoint Medical Center LLC
state: Missouri
city: Kansas City
country: United States
facility: Truman Medical Center
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Kansas City
country: United States
facility: Radiation Oncology Practice Corporation South
state: Missouri
city: Kansas City
country: United States
facility: Saint Joseph Health Center
state: Missouri
city: Kansas City
country: United States
facility: North Kansas City Hospital
state: Missouri
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Kansas City
country: United States
facility: Radiation Oncology Practice Corporation - North
state: Missouri
city: Lee's Summit
country: United States
facility: Saint Luke's East - Lee's Summit
state: Missouri
city: Liberty
country: United States
facility: Liberty Radiation Oncology Center
state: Missouri
city: Saint Joseph
country: United States
facility: Heartland Regional Medical Center
state: Missouri
city: Kearney
country: United States
facility: CHI Health Good Samaritan
state: Nebraska
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Brooklyn
country: United States
facility: New York-Presbyterian/Brooklyn Methodist Hospital
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Rochester
country: United States
facility: Highland Hospital
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Akron
country: United States
facility: Summa Akron City Hospital/Cooper Cancer Center
state: Ohio
city: Barberton
country: United States
facility: Summa Barberton Hospital
state: Ohio
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital - Dayton
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Health Center
state: Ohio
city: Dayton
country: United States
facility: Veteran Affairs Medical Center
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Hospital
state: Ohio
city: Franklin
country: United States
facility: Atrium Medical Center-Middletown Regional Hospital
state: Ohio
city: Kettering
country: United States
facility: Kettering Medical Center
state: Ohio
city: Salem
country: United States
facility: Cancer Care Center, Incorporated
state: Ohio
city: Troy
country: United States
facility: Upper Valley Medical Center
state: Ohio
city: Wilmington
country: United States
facility: Clinton Memorial Hospital
state: Ohio
city: Wooster
country: United States
facility: Cancer Treatment Center
state: Ohio
city: Wright-Patterson Air Force Base
country: United States
facility: Wright-Patterson Medical Center
state: Ohio
city: Xenia
country: United States
facility: Greene Memorial Hospital
state: Ohio
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Paoli
country: United States
facility: Paoli Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Einstein Medical Center Philadelphia
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: Main Line Health NCORP
state: Pennsylvania
city: Kingsport
country: United States
facility: Wellmont Holston Valley Hospital and Medical Center
state: Tennessee
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: American Fork
country: United States
facility: American Fork Hospital / Huntsman Intermountain Cancer Center
state: Utah
city: Cedar City
country: United States
facility: Sandra L Maxwell Cancer Center
state: Utah
city: Logan
country: United States
facility: Logan Regional Hospital
state: Utah
city: Murray
country: United States
facility: Cottonwood Hospital Medical Center
state: Utah
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Ogden
country: United States
facility: McKay-Dee Hospital Center
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center
state: Utah
city: Saint George
country: United States
facility: Dixie Medical Center Regional Cancer Center
state: Utah
city: Salt Lake City
country: United States
facility: Intermountain Health Care
state: Utah
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists-Salt Lake City
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Norton
country: United States
facility: Southwest VA Regional Cancer Center
state: Virginia
city: Yakima
country: United States
facility: North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
state: Washington
city: La Crosse
country: United States
facility: Gundersen Lutheran Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert and the Medical College of Wisconsin
state: Wisconsin
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Montreal
country: Canada
facility: McGill University Department of Oncology
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Radiation Therapy Oncology Group
name: Tracey Schefter
role: PRINCIPAL_INVESTIGATOR
References: