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

NCT00369122 | Completed Phase 2 Results

• 5 other identifiers: NCI-2009-00722CDR0000493005RTOG 0417RTOG-0417U10CA021661
• Study Type: interventional
• Target: 60
• Locations: 2 countries
• Sites: 106

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.

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

Outcome Measures

Primary Outcomes (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.

  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 Outcomes (3)

• 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.

• Disease-free Survival (Three-year Rate Reported)

  From registration to 3 years

• Overall Survival (Three-year Rate Reported)

  From registration to 3 years

Study Arms (1)

Treatment (radiation therapy, bevacizumab, cisplatin)

EXPERIMENTAL

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; Drug: Cisplatin; Radiation: External Beam Radiation Therapy; Radiation: Internal Radiation Therapy

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: 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

Treatment (radiation therapy, bevacizumab, cisplatin)

Cisplatin DRUG

Given IV

Also known as: 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

Treatment (radiation therapy, bevacizumab, cisplatin)

External Beam Radiation Therapy RADIATION

Undergo EBRT

Also known as: Definitive Radiation Therapy, EBRT, External Beam Radiotherapy, External Beam RT, external radiation, External Radiation Therapy, external-beam radiation

Treatment (radiation therapy, bevacizumab, cisplatin)

Internal Radiation Therapy RADIATION

Undergo brachytherapy

Also known as: BRACHYTHERAPY, internal radiation, Internal Radiation Brachytherapy, Radiation Brachytherapy

Treatment (radiation therapy, bevacizumab, cisplatin)

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• Radiation Therapy Oncology Group: collaborator

Study Sites (106)

Providence Saint Joseph Medical Center/Disney Family Cancer Center

Burbank, California, 91505, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Penrose-Saint Francis Healthcare

Colorado Springs, Colorado, 80907, United States

Location

University of Colorado

Denver, Colorado, 80217-3364, United States

Location

Baptist MD Anderson Cancer Center

Jacksonville, Florida, 32207, United States

Location

Integrated Community Oncology Network-Southside Cancer Center

Jacksonville, Florida, 32207, United States

Location

University of Florida Health Science Center - Jacksonville

Jacksonville, Florida, 32209, United States

Location

Baptist Medical Center South

Jacksonville, Florida, 32258, United States

Location

Integrated Community Oncology Network-Florida Cancer Center Beaches

Jacksonville Beach, Florida, 32250, United States

Location

21st Century Oncology-Orange Park

Orange Park, Florida, 32073, United States

Location

UF Cancer Center at Orlando Health

Orlando, Florida, 32806, United States

Location

21st Century Oncology-Palatka

Palatka, Florida, 32177, United States

Location

Bay Medical Center

Panama City, Florida, 32401, United States

Location

Integrated Community Oncology Network-Flager Cancer Center

Saint Augustine, Florida, 32086, United States

Location

Grady Health System

Atlanta, Georgia, 30303, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Northwest Community Hospital

Arlington Heights, Illinois, 60005, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

John H Stroger Jr Hospital of Cook County

Chicago, Illinois, 60612, United States

Location

Franciscan St. James Health-Olympia Fields Campus

Olympia Fields, Illinois, 60461, United States

Location

Methodist Medical Center of Illinois

Peoria, Illinois, 61603, United States

Location

Saint Vincent Anderson Regional Hospital/Cancer Center

Anderson, Indiana, 46016, United States

Location

Franciscan Saint Francis Health-Beech Grove

Beech Grove, Indiana, 46107, United States

Location

Saint Vincent Hospital and Health Care Center

Indianapolis, Indiana, 46260, United States

Location

Reid Health

Richmond, Indiana, 47374, United States

Location

Providence Medical Center

Kansas City, Kansas, 66112, United States

Location

Lawrence Memorial Hospital

Lawrence, Kansas, 66044, United States

Location

Menorah Medical Center

Overland Park, Kansas, 66209, United States

Location

Radiation Oncology Practice Corporation Southwest

Overland Park, Kansas, 66210, United States

Location

Saint Luke's South Hospital

Overland Park, Kansas, 66213, United States

Location

Shawnee Mission Medical Center-KCCC

Shawnee Mission, Kansas, 66204, United States

Location

Baptist Health Lexington

Lexington, Kentucky, 40503, United States

Location

Norton Suburban Hospital and Medical Campus

Louisville, Kentucky, 40207, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Borgess Medical Center

Kalamazoo, Michigan, 49001, United States

Location

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007, United States

Location

Cape Radiation Oncology

Cape Girardeau, Missouri, 63703, United States

Location

Centerpoint Medical Center LLC

Independence, Missouri, 64057, United States

Location

Truman Medical Center

Kansas City, Missouri, 64108, United States

Location

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, 64111, United States

Location

Radiation Oncology Practice Corporation South

Kansas City, Missouri, 64114, United States

Location

Saint Joseph Health Center

Kansas City, Missouri, 64114, United States

Location

North Kansas City Hospital

Kansas City, Missouri, 64116, United States

Location

Research Medical Center

Kansas City, Missouri, 64132, United States

Location

Radiation Oncology Practice Corporation - North

Kansas City, Missouri, 64154, United States

Location

Saint Luke's East - Lee's Summit

Lee's Summit, Missouri, 64086, United States

Location

Liberty Radiation Oncology Center

Liberty, Missouri, 64068, United States

Location

Heartland Regional Medical Center

Saint Joseph, Missouri, 64506, United States

Location

CHI Health Good Samaritan

Kearney, Nebraska, 68847, United States

Location

University Medical Center of Southern Nevada

Las Vegas, Nevada, 89102, United States

Location

Saint Barnabas Medical Center

Livingston, New Jersey, 07039, United States

Location

Monmouth Medical Center

Long Branch, New Jersey, 07740, United States

Location

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08903, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

New York-Presbyterian/Brooklyn Methodist Hospital

Brooklyn, New York, 11215, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Highland Hospital

Rochester, New York, 14620, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Summa Akron City Hospital/Cooper Cancer Center

Akron, Ohio, 44304, United States

Location

Summa Barberton Hospital

Barberton, Ohio, 44203, United States

Location

Grandview Hospital

Dayton, Ohio, 45405, United States

Location

Good Samaritan Hospital - Dayton

Dayton, Ohio, 45406, United States

Location

Miami Valley Hospital

Dayton, Ohio, 45409, United States

Location

Samaritan North Health Center

Dayton, Ohio, 45415, United States

Location

Veteran Affairs Medical Center

Dayton, Ohio, 45428, United States

Location

Blanchard Valley Hospital

Findlay, Ohio, 45840, United States

Location

Atrium Medical Center-Middletown Regional Hospital

Franklin, Ohio, 45005-1066, United States

Location

Kettering Medical Center

Kettering, Ohio, 45429, United States

Location

Cancer Care Center, Incorporated

Salem, Ohio, 44460, United States

Location

Upper Valley Medical Center

Troy, Ohio, 45373, United States

Location

Clinton Memorial Hospital

Wilmington, Ohio, 45177, United States

Location

Cancer Treatment Center

Wooster, Ohio, 44691, United States

Location

Wright-Patterson Medical Center

Wright-Patterson Air Force Base, Ohio, 45433-5529, United States

Location

Greene Memorial Hospital

Xenia, Ohio, 45385, United States

Location

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, 19010, United States

Location

Paoli Memorial Hospital

Paoli, Pennsylvania, 19301, United States

Location

Einstein Medical Center Philadelphia

Philadelphia, Pennsylvania, 19141, United States

Location

Reading Hospital

West Reading, Pennsylvania, 19611, United States

Location

Lankenau Medical Center

Wynnewood, Pennsylvania, 19096, United States

Location

Main Line Health NCORP

Wynnewood, Pennsylvania, 19096, United States

Location

Wellmont Holston Valley Hospital and Medical Center

Kingsport, Tennessee, 37660, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

American Fork Hospital / Huntsman Intermountain Cancer Center

American Fork, Utah, 84003, United States

Location

Sandra L Maxwell Cancer Center

Cedar City, Utah, 84720, United States

Location

Logan Regional Hospital

Logan, Utah, 84321, United States

Location

Cottonwood Hospital Medical Center

Murray, Utah, 84107, United States

Location

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

McKay-Dee Hospital Center

Ogden, Utah, 84403, United States

Location

Utah Valley Regional Medical Center

Provo, Utah, 84604, United States

Location

Intermountain Health Care

Salt Lake City, Utah, 84103, United States

Location

Utah Cancer Specialists-Salt Lake City

Salt Lake City, Utah, 84106, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

LDS Hospital

Salt Lake City, Utah, 84143, United States

Location

Dixie Medical Center Regional Cancer Center

St. George, Utah, 84770, United States

Location

Southwest VA Regional Cancer Center

Norton, Virginia, 24273, United States

Location

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital

Yakima, Washington, 98902, United States

Location

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, 54601, United States

Location

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

McGill University Department of Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Brachytherapy

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Radiotherapy; Therapeutics

Limitations and 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.

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: Radiation Therapy Oncology Group (RTOG)

wseiferheld@acr.org

Study Officials

• Tracey Schefter

  Radiation Therapy Oncology Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2006
• First Posted: August 29, 2006
• Study Start: August 11, 2006
• Primary Completion: June 4, 2010
• Study Completion: December 15, 2016
• Last Updated: March 20, 2018
• Results First Posted: May 17, 2013

Record last verified: 2018-02

Locations

US (103); CA (3)