Paclitaxel and Cisplatin or Topotecan With or Without Bevacizumab in Treating Patients With Stage IVB, Recurrent, or Persistent Cervical Cancer

NCT00803062CompletedPHASE3INTERVENTIONAL

Summary

This randomized phase III trial studies the side effects of paclitaxel when given together with cisplatin or topotecan with or without bevacizumab and to compare how well they work in treating patients with stage IVB, cervical cancer that has come back or is persistent. Drugs used in chemotherapy, such as paclitaxel, cisplatin, and topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether paclitaxel is more effective when given together with cisplatin or topotecan with or without bevacizumab in treating patients with cervical cancer.

Key Facts

Lead Sponsor

National Cancer Institute (NCI)

Enrollment

452

Start Date

2009-04-01

Completion Date

2013-02-01

Study Type

INTERVENTIONAL

Official Title

A Randomized Phase III Trial of Cisplatin Plus Paclitaxel With and Without NCI-Supplied Bevacizumab (NSC #704865) Versus the Non-platinum Doublet, Topotecan Plus Paclitaxel, With and Without NCI-Supplied Bevacizumab, in Stage IVB, Recurrent or Persistent Carcinoma of the Cervix

Interventions

BevacizumabCisplatinLaboratory Biomarker AnalysisPaclitaxelQuality-of-Life AssessmentQuestionnaire AdministrationTopotecan Hydrochloride

Conditions

Cervical AdenocarcinomaCervical Adenosquamous CarcinomaCervical Squamous Cell CarcinomaRecurrent Cervical CarcinomaStage IVB Cervical Cancer

Eligibility

Age Range

18 Years+

Sex

FEMALE

Inclusion Criteria:

* Patients must have primary stage IVB, recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy
* All patients must have measurable disease; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each lesion must be \>= 20 mm when measured by conventional techniques, including palpation, plain x-ray, computed tomography (CT), and magnetic resonance imaging (MRI), or \>= 10 mm when measured by spiral CT; biopsy confirmation is required if the lesion(s) measures \< 30 mm or if the treating physician determines it is clinically indicated; patients must have at least one "target lesion" to be used to assess response on this protocol as defined by Response Evaluation Criteria in Solid Tumors (RECIST); this lesion should be the one that was biopsied if one was performed; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
* Absolute neutrophil count (ANC) \>= 1500/mcl
* Platelets \>= 100,000/mcl
* Serum creatinine =\< upper limit of normal (ULN) (Common Toxicity Criteria \[CTC\] grade 0) or calculated creatinine clearance (Jeliffe formula) \>= 60 ml/min
* Bilirubin =\< 1.5 x institutional normal
* Serum glutamic oxaloacetic transaminase (SGOT) =\< 2.5 x institutional normal
* Alkaline phosphatase =\< 2.5 x institutional normal
* Prothrombin time (PT) such that international normalized ratio (INR) is =\< 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thrombo-embolus)
* Partial thromboplastin time (PTT) \< 1.2 times the upper limit of normal
* Urine protein-creatinine ratio (UPC ratio) \< 1.0
* Patients must have a GOG performance status of 0 or 1
* Patients must have recovered from the effects of surgery, radiation therapy, or chemoradiotherapy; at least six weeks must have elapsed from the last administration of chemoradiotherapy, and at least three weeks must have elapsed from the last administration of radiation therapy alone; at least six weeks must have elapsed from the time of any major surgical procedure prior to randomization
* Patients must have signed an approved informed consent and authorization permitting release of personal health information
* Patients must meet all of the pre-entry requirements, including baseline QOL questionnaire
* Patients must be free of active infection requiring antibiotics

Exclusion Criteria:

* Patients with bilateral hydronephrosis which cannot be alleviated by ureteral stents or percutaneous drainage
* Patients previously treated with chemotherapy except when used concurrently with radiation therapy

  * Patients who have received concurrent paclitaxel and/or concurrent topotecan with radiation therapy are ineligible
* Patients with craniospinal metastases
* Patients with a concomitant malignancy other than non-melanoma skin cancer
* Patients with a prior invasive malignancy (except non-melanoma skin cancer) who have had any evidence of disease within the last 5 years or whose prior malignancy treatment contraindicates the current protocol therapy
* Patients with serious non-healing wound, ulcer, or bone fracture; this includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess for which an interval of 3 to 6 months must pass before study entry; in addition, the patient must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the fistula/perforation; patients with granulating incisions healing by secondary intention with no evidence of fascial dehiscence or infection are eligible but require weekly wound examinations
* Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
* Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study
* Patients with clinically significant cardiovascular disease; this includes:

  * Uncontrolled hypertension, defined as systolic \> 150 mm Hg or diastolic \> 90 mm Hg
  * Myocardial infarction or unstable angina \< 6 months prior to registration
  * New York Heart Association (NYHA) grade II or greater congestive heart failure
  * Serious cardiac arrhythmia requiring medication; this does not include asymptomatic, atrial fibrillation with controlled ventricular rate
  * CTCAE grade 2 or greater peripheral vascular disease (at least brief \[\< 24 hours (hrs)\]) episodes of ischemia managed non-surgically and without permanent deficit)
  * History of CVA within six months
* Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
* Patients with or with anticipation of invasive procedures as defined below:

  * Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of bevacizumab therapy
  * Major surgical procedure anticipated during the course of the study; this includes, but is not limited to abdominal surgery (laparotomy or laparoscopy) prior to disease progression, such as colostomy or enterostomy reversal, interval or secondary cytoreductive surgery, or second look surgery; please consult with the study chair prior to patient entry for any questions related to the classification of surgical procedures
  * Core biopsy, within 7 days prior to randomization
* Patients who are pregnant or nursing; bevacizumab should not be administered to pregnant women; bevacizumab should not be administered to nursing women; patients of childbearing potential must agree to use contraceptive measures during study therapy and for at least six months after completion of bevacizumab therapy
* Patients who have received prior therapy with any anti-vascular endothelial growth factor (VEGF) drug, including bevacizumab
* Patients with clinical symptoms or signs of gastrointestinal obstruction and who require parenteral hydration and/or nutrition
* Patients with medical history or conditions not otherwise previously specified which in the opinion of the investigator should exclude participation in this study; the investigator should feel free to consult the Study Chair or Study Co-Chairs for uncertainty in this regard
* Patients with significant peripheral vascular disease
* Patients with pre-existing grade 2 or greater peripheral neuropathy

Outcome Measures

Primary Outcomes

Overall Survival

The observed length of life from randomization into the study to death or the date of last contact.

Time frame: From entry into the study to death or the date of last contact, assessed up to 5 years

Progression-free Survival

Disease that can be assessed clinically (physical examination) should be evaluated every cycle (every 3 weeks). Disease assessed by imaging modalities (CXR, CT, MRI) should be evaluated every other cycle unless other evidence of a change mandates earlier assessment. Tumor measurements should also be done after the final cycle (if the patient is taken off of study therapy for a reason other than progression) and then every 3 months x 2 years (followed with every 6 months x 3 years) until progression is documented. "Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions assessed radiographically and 50% increase if the only target lesion is a solitary pelvic mass measured by physical exam, or unequivocal progression of a non-target lesion, or the appearance of new lesions", or similar definition as accurate and appropriate.

Time frame: From study entry until disease progression, death or date of last contact, assessed up to 5 years (During treatment: every 3 weeks if by physical exam, every 6 weeks by CXR, CT or MRI. In follow-up: quarterly for 2 years then semi-annually for 3 years)

Tumor Response

Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions by CT, MRI or CXR. If the only target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% increase in longest diameter is required; Overall Response (OR) = CR + PR.

Time frame: Every cycle (if assessed by physical exam), every other cycle (if assessed by imaging), after the final cycle, then every 3 months x 2 years, then every 6 months x 3 years up to 5 years.

To Determine and Compare the Frequency and Severity of Adverse Events as Assessed by CTCAE Version 3.0 for the Regimens Administered on This Study.

The number of patients on each arm who have Grade 3 AE or higher toxicity.

Time frame: From date of enrollment until 30 days after treatment completion

Locations

University of Alabama at Birmingham Cancer Center, Birmingham, United States

University of South Alabama Mitchell Cancer Institute, Mobile, United States

Saint Joseph's Hospital and Medical Center, Phoenix, United States

Highlands Oncology Group PA - Fayetteville, Fayetteville, United States

Washington Regional Medical Center - Fayetteville, Fayetteville, United States

University of Arkansas for Medical Sciences, Little Rock, United States

Alta Bates Summit Medical Center-Herrick Campus, Berkeley, United States

Providence Saint Joseph Medical Center/Disney Family Cancer Center, Burbank, United States

Roy and Patricia Disney Family Cancer Center, Burbank, United States

Mills - Peninsula Hospitals, Burlingame, United States

John Muir Medical Center-Concord Campus, Concord, United States

City of Hope Comprehensive Cancer Center, Duarte, United States

California Cancer Center - North Fresno, Fresno, United States

Long Beach Memorial Medical Center-Todd Cancer Institute, Long Beach, United States

Kaiser Permanente Los Angeles Medical Center, Los Angeles, United States

Los Angeles County-USC Medical Center, Los Angeles, United States

USC / Norris Comprehensive Cancer Center, Los Angeles, United States

UCLA / Jonsson Comprehensive Cancer Center, Los Angeles, United States

Palo Alto Medical Foundation-Gynecologic Oncology, Mountain View, United States

Sutter Cancer Research Consortium, Novato, United States

Saint Joseph Hospital - Orange, Orange, United States

UC Irvine Health/Chao Family Comprehensive Cancer Center, Orange, United States

Stanford Cancer Institute, Palo Alto, United States

University of California Davis Comprehensive Cancer Center, Sacramento, United States

University of California San Diego, San Diego, United States

UCSF Medical Center-Mount Zion, San Francisco, United States

California Pacific Medical Center-Pacific Campus, San Francisco, United States

Olive View-University of California Los Angeles Medical Center, Sylmar, United States

Sutter Solano Medical Center/Cancer Center, Vallejo, United States

John Muir Medical Center-Walnut Creek, Walnut Creek, United States

Colorado Gynecologic Oncology Group, Aurora, United States

The Medical Center of Aurora, Aurora, United States

University of Colorado Cancer Center - Anschutz Cancer Pavilion, Aurora, United States

Boulder Community Hospital, Boulder, United States

Penrose-Saint Francis Healthcare, Colorado Springs, United States

Porter Adventist Hospital, Denver, United States

Exempla Saint Joseph Hospital, Denver, United States

Presbyterian - Saint Lukes Medical Center - Health One, Denver, United States

Rose Medical Center, Denver, United States

Colorado Cancer Research Program CCOP, Denver, United States

Rocky Mountain Gynecologic Oncology PC, Englewood, United States

Swedish Medical Center, Englewood, United States

Poudre Valley Hospital, Fort Collins, United States

Front Range Cancer Specialists, Fort Collins, United States

Saint Mary's Hospital and Regional Medical Center, Grand Junction, United States

North Colorado Medical Center, Greeley, United States

Saint Anthony Hospital, Lakewood, United States

Littleton Adventist Hospital, Littleton, United States

Sky Ridge Medical Center, Lone Tree, United States

Longmont United Hospital, Longmont, United States

McKee Medical Center, Loveland, United States

Parker Adventist Hospital, Parker, United States

Saint Mary Corwin Medical Center, Pueblo, United States

North Suburban Medical Center, Thornton, United States

Exempla Lutheran Medical Center, Wheat Ridge, United States

Hartford Hospital, Hartford, United States

Saint Francis Hospital and Medical Center, Hartford, United States

The Hospital of Central Connecticut, New Britain, United States

Beebe Medical Center, Lewes, United States

Christiana Care Health System-Christiana Hospital, Newark, United States

Washington Hospital Center, Washington D.C., United States

Broward Health Medical Center, Fort Lauderdale, United States

Florida Gynecologic Oncology, Fort Myers, United States

Memorial Healthcare System - Joe DiMaggio Children's Hospital, Hollywood, United States

Mayo Clinic in Florida, Jacksonville, United States

Lakeland Regional Cancer Center, Lakeland, United States

Florida Hospital Orlando, Orlando, United States

UF Cancer Center at Orlando Health, Orlando, United States

Sarasota Memorial Hospital, Sarasota, United States

Moffitt Cancer Center, Tampa, United States

Grady Health System, Atlanta, United States

Piedmont Hospital, Atlanta, United States

Emory University/Winship Cancer Institute, Atlanta, United States

Atlanta Regional CCOP, Atlanta, United States

Northside Hospital, Atlanta, United States

Saint Joseph's Hospital of Atlanta, Atlanta, United States

Georgia Regents University Medical Center, Augusta, United States

Well Star Cobb Hospital, Austell, United States

John B Amos Cancer Center, Columbus, United States

Dekalb Medical Center, Decatur, United States

Piedmont Fayette Hospital, Fayetteville, United States

Northeast Georgia Medical Center, Gainesville, United States

Gwinnett Medical Center, Lawrenceville, United States

Central Georgia Gynecologic Oncology, Macon, United States

Wellstar Kennestone Hospital, Marietta, United States

Southern Regional Medical Center, Riverdale, United States

Harbin Clinic Medical Oncology and Clinical Research, Rome, United States

Memorial University Medical Center, Savannah, United States

Oncare Hawaii Inc-POB II, Honolulu, United States

Queen's Medical Center, Honolulu, United States

Straub Clinic and Hospital, Honolulu, United States

University of Hawaii Cancer Center, Honolulu, United States

Oncare Hawaii Inc-Kuakini, Honolulu, United States

The Cancer Center of Hawaii-Liliha, Honolulu, United States

Kapiolani Medical Center for Women and Children, Honolulu, United States

Wilcox Memorial Hospital and Kauai Medical Clinic, Lihue, United States

Maui Memorial Medical Center, Wailuku, United States

Pacific Cancer Institute of Maui, Wailuku, United States

Pali Momi Medical Center, ‘Aiea, United States

Saint Alphonsus Cancer Care Center-Boise, Boise, United States

Saint Joseph Medical Center, Bloomington, United States

Illinois CancerCare-Bloomington, Bloomington, United States

Graham Hospital Association, Canton, United States

Illinois CancerCare-Canton, Canton, United States

Illinois CancerCare-Carthage, Carthage, United States

Memorial Hospital, Carthage, United States

Mount Sinai Hospital Medical Center, Chicago, United States

Northwestern University, Chicago, United States

John H Stroger Jr Hospital of Cook County, Chicago, United States

Rush University Medical Center, Chicago, United States

Swedish Covenant Hospital, Chicago, United States

University of Chicago Comprehensive Cancer Center, Chicago, United States

Decatur Memorial Hospital, Decatur, United States

Eureka Hospital, Eureka, United States

Illinois CancerCare-Eureka, Eureka, United States

Saint Francis Hospital, Evanston, United States

Illinois CancerCare Galesburg, Galesburg, United States

Illinois CancerCare-Havana, Havana, United States

Mason District Hospital, Havana, United States

Sudarshan K Sharma MD Limted-Gynecologic Oncology, Hinsdale, United States

Joliet Oncology-Hematology Associates Limited, Joliet, United States

Presence Saint Mary's Hospital, Kankakee, United States

Illinois CancerCare-Kewanee Clinic, Kewanee, United States

Illinois CancerCare-Macomb, Macomb, United States

Mcdonough District Hospital, Macomb, United States

Loyola University Medical Center, Maywood, United States

Holy Family Medical Center, Monmouth, United States

Illinois CancerCare-Monmouth, Monmouth, United States

Bromenn Regional Medical Center, Normal, United States

Community Cancer Center Foundation, Normal, United States

Illinois CancerCare-Community Cancer Center, Normal, United States

Advocate Christ Medical Center, Oak Lawn, United States

Illinois CancerCare-Ottawa Clinic, Ottawa, United States

Ottawa Regional Hospital and Healthcare Center, Ottawa, United States

Advocate Lutheran General Hospital., Park Ridge, United States

Illinois CancerCare-Pekin, Pekin, United States

Pekin Cancer Treatment Center, Pekin, United States

Methodist Medical Center of Illinois, Peoria, United States

Proctor Hospital, Peoria, United States

Illinois CancerCare-Peoria, Peoria, United States

Illinois Oncology Research Association CCOP, Peoria, United States

OSF Saint Francis Medical Center, Peoria, United States

Illinois CancerCare-Peru, Peru, United States

Illinois Valley Hospital, Peru, United States

Illinois CancerCare-Princeton, Princeton, United States

Perry Memorial Hospital, Princeton, United States

Illinois CancerCare-Spring Valley, Spring Valley, United States

Memorial Medical Center, Springfield, United States

Cadence Cancer Center in Warrenville, Warrenville, United States

Saint Francis Hospital and Health Centers, Beech Grove, United States

Elkhart Clinic, Elkhart, United States

Michiana Hematology Oncology PC-Elkhart, Elkhart, United States

Elkhart General Hospital, Elkhart, United States

Fort Wayne Medical Oncology and Hematology Inc-Parkview, Fort Wayne, United States

Indiana University/Melvin and Bren Simon Cancer Center, Indianapolis, United States

Franciscan Saint Francis Health-Indianapolis, Indianapolis, United States

Gynecologic Oncology of Indiana, Indianapolis, United States

Saint Vincent Hospital and Health Services, Indianapolis, United States

Saint Vincent Oncology Center, Indianapolis, United States

Community Howard Regional Health, Kokomo, United States

IU Health La Porte Hospital, La Porte, United States

Michiana Hematology Oncology PC-Mishawaka, Mishawaka, United States

Saint Joseph Regional Medical Center-Mishawaka, Mishawaka, United States

The Community Hospital, Munster, United States

Michiana Hematology Oncology PC-Plymouth, Plymouth, United States

Reid Hospital and Health Care Services, Richmond, United States

Memorial Hospital of South Bend, South Bend, United States

Michiana Hematology Oncology PC-South Bend, South Bend, United States

South Bend Clinic, South Bend, United States

Northern Indiana Cancer Research Consortium CCOP, South Bend, United States

Michiana Hematology Oncology-PC Westville, Westville, United States

McFarland Clinic PC-William R Bliss Cancer Center, Ames, United States

Medical Oncology and Hematology Associates-West Des Moines, Clive, United States

Mercy Capitol, Des Moines, United States

Iowa Methodist Medical Center, Des Moines, United States

Iowa Oncology Research Association CCOP, Des Moines, United States

Medical Oncology and Hematology Associates-Des Moines, Des Moines, United States

Medical Oncology and Hematology Associates-Laurel, Des Moines, United States

Mercy Medical Center - Des Moines, Des Moines, United States

Iowa Lutheran Hospital, Des Moines, United States

University of Iowa/Holden Comprehensive Cancer Center, Iowa City, United States

Mercy Medical Center-Sioux City, Sioux City, United States

Saint Luke's Regional Medical Center, Sioux City, United States

Hospital District Sixth of Harper County, Anthony, United States

Cancer Center of Kansas - Chanute, Chanute, United States

Cancer Center of Kansas - Dodge City, Dodge City, United States

Cancer Center of Kansas - El Dorado, El Dorado, United States

Cancer Center of Kansas - Fort Scott, Fort Scott, United States

Cancer Center of Kansas-Independence, Independence, United States

University of Kansas Cancer Center, Kansas City, United States

Cancer Center of Kansas-Kingman, Kingman, United States

Lawrence Memorial Hospital, Lawrence, United States

Cancer Center of Kansas-Liberal, Liberal, United States

Cancer Center of Kansas - McPherson, McPherson, United States

Cancer Center of Kansas - Newton, Newton, United States

Menorah Medical Center, Overland Park, United States

Saint Luke's South Hospital, Overland Park, United States

Cancer Center of Kansas - Parsons, Parsons, United States

Kansas City CCOP, Prairie Village, United States

Cancer Center of Kansas - Pratt, Pratt, United States

Cancer Center of Kansas - Salina, Salina, United States

Shawnee Mission Medical Center, Shawnee Mission, United States

Cancer Center of Kansas - Wellington, Wellington, United States

Associates In Womens Health, Wichita, United States

Cancer Center of Kansas-Wichita Medical Arts Tower, Wichita, United States

Cancer Center of Kansas - Main Office, Wichita, United States

Via Christi Regional Medical Center, Wichita, United States

Wichita CCOP, Wichita, United States

Cancer Center of Kansas - Winfield, Winfield, United States

Saint Elizabeth Medical Center South, Edgewood, United States

Baptist Health Lexington, Lexington, United States

University of Kentucky/Markey Cancer Center, Lexington, United States

Norton Hospital Pavilion and Medical Campus, Louisville, United States

Doctors Carrol, Sheth, Raghavan, Louisville, United States

Pikeville Medical Center, Pikeville, United States

Hematology/Oncology Clinic LLP, Baton Rouge, United States

Woman's Hospital, Baton Rouge, United States

Tulane University Health Sciences Center, New Orleans, United States

Ochsner Medical Center Jefferson, New Orleans, United States

Louisiana State University Health Sciences Center Shreveport, Shreveport, United States

Highland Clinic, Shreveport, United States

Maine Medical Center-Bramhall Campus, Portland, United States

University of Maryland/Greenebaum Cancer Center, Baltimore, United States

Greater Baltimore Medical Center, Baltimore, United States

Sinai Hospital of Baltimore, Baltimore, United States

Franklin Square Hospital Center, Baltimore, United States

Union Hospital of Cecil County, Elkton, United States

Tufts Medical Center, Boston, United States

Massachusetts General Hospital Cancer Center, Boston, United States

Brigham and Women's Hospital, Boston, United States

Dana-Farber Cancer Institute, Boston, United States

Baystate Medical Center, Springfield, United States

University of Massachusetts Memorial Health Care, Worcester, United States

Saint Joseph Mercy Hospital, Ann Arbor, United States

Michigan Cancer Research Consortium CCOP, Ann Arbor, United States

Bronson Battle Creek, Battle Creek, United States

Spectrum Health Big Rapids Hospital, Big Rapids, United States

Oakwood Hospital and Medical Center, Dearborn, United States

Wayne State University/Karmanos Cancer Institute, Detroit, United States

Henry Ford Hospital, Detroit, United States

Saint John Hospital and Medical Center, Detroit, United States

Green Bay Oncology - Escanaba, Escanaba, United States

Hurley Medical Center, Flint, United States

Genesys Regional Medical Center-West Flint Campus, Flint, United States

Grand Rapids Clinical Oncology Program, Grand Rapids, United States

Mercy Health Saint Mary's, Grand Rapids, United States

Spectrum Health at Butterworth Campus, Grand Rapids, United States

Green Bay Oncology - Iron Mountain, Iron Mountain, United States

Allegiance Health, Jackson, United States

Borgess Medical Center, Kalamazoo, United States

Bronson Methodist Hospital, Kalamazoo, United States

West Michigan Cancer Center, Kalamazoo, United States

Sparrow Hospital, Lansing, United States

Saint Mary Mercy Hospital, Livonia, United States

Mid-Michigan Medical Center - Midland, Midland, United States

Mercy Health Mercy Campus, Muskegon, United States

Michiana Hematology Oncology PC-Niles, Niles, United States

Saint Joseph Mercy Oakland, Pontiac, United States

Saint Joseph Mercy Port Huron, Port Huron, United States

William Beaumont Hospital-Royal Oak, Royal Oak, United States

Saint Mary's of Michigan, Saginaw, United States

Lakeland Hospital, Saint Joseph, United States

Marie Yeager Cancer Center, Saint Joseph, United States

Providence Hospital, Southfield, United States

Munson Medical Center, Traverse City, United States

Saint John Macomb-Oakland Hospital, Warren, United States

Metro Health Hospital, Wyoming, United States

Fairview Ridges Hospital, Burnsville, United States

Mercy Hospital, Coon Rapids, United States

Fairview-Southdale Hospital, Edina, United States

Unity Hospital, Fridley, United States

Hutchinson Area Health Care, Hutchinson, United States

Minnesota Oncology Hematology PA-Maplewood, Maplewood, United States

Saint John's Hospital - Healtheast, Maplewood, United States

Abbott-Northwestern Hospital, Minneapolis, United States

Hennepin County Medical Center, Minneapolis, United States

University of Minnesota Medical Center-Fairview, Minneapolis, United States

North Memorial Medical Health Center, Robbinsdale, United States

Mayo Clinic, Rochester, United States

Metro-Minnesota NCI Community Oncology Research Program, Saint Louis Park, United States

Park Nicollet Clinic - Saint Louis Park, Saint Louis Park, United States

Regions Hospital, Saint Paul, United States

United Hospital, Saint Paul, United States

Saint Francis Regional Medical Center, Shakopee, United States

Lakeview Hospital, Stillwater, United States

Ridgeview Medical Center, Waconia, United States

Rice Memorial Hospital, Willmar, United States

Minnesota Oncology and Hematology PA-Woodbury, Woodbury, United States

University of Mississippi Medical Center, Jackson, United States

Singing River Hospital, Pascagoula, United States

Truman Medical Center, Kansas City, United States

Saint Luke's Cancer Institute, Kansas City, United States

Saint Luke's Hospital of Kansas City, Kansas City, United States

Saint Joseph Health Center, Kansas City, United States

North Kansas City Hospital, Kansas City, United States

Heartland Hematology and Oncology Associates Incorporated, Kansas City, United States

Research Medical Center, Kansas City, United States

Saint Luke's East - Lee's Summit, Lee's Summit, United States

Liberty Hospital, Liberty, United States

Liberty Radiation Oncology Center, Liberty, United States

Phelps County Regional Medical Center, Rolla, United States

Heartland Regional Medical Center, Saint Joseph, United States

Saint Joseph Oncology Inc, Saint Joseph, United States

Mercy Hospital Springfield, Springfield, United States

Ozark Health Ventures LLC-Cancer Research for The Ozarks Springfield, Springfield, United States

CoxHealth South Hospital, Springfield, United States

Saint Louis University Hospital, St Louis, United States

Montana Cancer Consortium CCOP, Billings, United States

Northern Rockies Radiation Oncology Center, Billings, United States

Saint Vincent Healthcare, Billings, United States

Frontier Cancer Center and Blood Institute-Billings, Billings, United States

Billings Clinic Cancer Center, Billings, United States

Bozeman Deaconess Cancer Center, Bozeman, United States

Bozeman Deaconess Hospital, Bozeman, United States

Saint James Community Hospital and Cancer Treatment Center, Butte, United States

Benefis Healthcare- Sletten Cancer Institute, Great Falls, United States

Berdeaux, Donald MD (UIA Investigator), Great Falls, United States

Great Falls Clinic, Great Falls, United States

Northern Montana Hospital, Havre, United States

Saint Peter's Community Hospital, Helena, United States

Glacier Oncology PLLC, Kalispell, United States

Kalispell Medical Oncology, Kalispell, United States

Kalispell Regional Medical Center, Kalispell, United States

Community Medical Hospital, Missoula, United States

Montana Cancer Specialists, Missoula, United States

Saint Patrick Hospital - Community Hospital, Missoula, United States

Guardian Oncology and Center for Wellness, Missoula, United States

Nebraska Methodist Hospital, Omaha, United States

University of Nebraska Medical Center, Omaha, United States

Women's Cancer Center of Nevada, Las Vegas, United States

Center of Hope at Renown Medical Center, Reno, United States

Renown Regional Medical Center, Reno, United States

Dartmouth Hitchcock Medical Center, Lebanon, United States

Cooper Hospital University Medical Center, Camden, United States

Morristown Memorial Hospital, Morristown, United States

Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County, Mount Holly, United States

Jersey Shore Medical Center, Neptune City, United States

Rutgers Cancer Institute of New Jersey, New Brunswick, United States

UMDNJ - New Jersey Medical School, Newark, United States

The Women's Institute for Gynecologic Cancer and Special Pelvic Surgery, Phillipsburg, United States

Valley Hospital, Ridgewood, United States

Overlook Hospital, Summit, United States

Inspira Medical Center Vineland, Vineland, United States

Virtua West Jersey Hospital Voorhees, Voorhees Township, United States

Southwest Gynecologic Oncology Associates Inc, Albuquerque, United States

University of New Mexico Cancer Center, Albuquerque, United States

Women's Cancer Care Associates LLC, Albany, United States

Island Gynecologic Oncology, Brightwaters, United States

State University of New York Downstate Medical Center, Brooklyn, United States

Queens Hospital Center, Jamaica, United States

North Shore University Hospital, Manhasset, United States

North Shore-LIJ Health System CCOP, Manhasset, United States

Orange Regional Medical Center, Middletown, United States

Long Island Jewish Medical Center, New Hyde Park, United States

North Shore-LIJ Health System/Center for Advanced Medicine, New Hyde Park, United States

Beth Israel Medical Center, New York, United States

New York University Langone Medical Center, New York, United States

Saint Luke's Roosevelt Hospital Center - Saint Luke's Division, New York, United States

Columbia University Medical Center, New York, United States

Memorial Sloan-Kettering Cancer Center, New York, United States

Weill Medical College of Cornell University, New York, United States

Stony Brook University Medical Center, Stony Brook, United States

State University of New York Upstate Medical University, Syracuse, United States

Montefiore Medical Center-Einstein Campus, The Bronx, United States

Randolph Hospital, Asheboro, United States

Hope Women's Cancer Centers-Asheville, Asheville, United States

Cone Health Cancer Center at Alamance Regional, Burlington, United States

University of North Carolina at Chapel Hill, Chapel Hill, United States

Carolinas Medical Center, Charlotte, United States

Novant Health Presbyterian Medical Center, Charlotte, United States

Wayne Memorial Hospital, Goldsboro, United States

Cone Health Cancer Center, Greensboro, United States

Kinston Medical Specialists PA, Kinston, United States

Annie Penn Memorial Hospital, Reidsville, United States

Rutherford Hospital, Rutherfordton, United States

Wake Forest University Health Sciences, Winston-Salem, United States

Mid Dakota Clinic, Bismarck, United States

Saint Alexius Medical Center, Bismarck, United States

Sanford Bismarck Medical Center, Bismarck, United States

Summa Akron City Hospital/Cooper Cancer Center, Akron, United States

Akron General Medical Center, Akron, United States

Mary Rutan Hospital, Bellefontaine, United States

Aultman Health Foundation, Canton, United States

Adena Regional Medical Center, Chillicothe, United States

Good Samaritan Hospital - Cincinnati, Cincinnati, United States

University of Cincinnati, Cincinnati, United States

Case Western Reserve University, Cleveland, United States

MetroHealth Medical Center, Cleveland, United States

Cleveland Clinic Cancer Center/Fairview Hospital, Cleveland, United States

Cleveland Clinic Foundation, Cleveland, United States

Ohio State University Comprehensive Cancer Center, Columbus, United States

Riverside Methodist Hospital, Columbus, United States

Columbus CCOP, Columbus, United States

Grant Medical Center, Columbus, United States

Mount Carmel Health Center West, Columbus, United States

Doctors Hospital, Columbus, United States

Grandview Hospital, Dayton, United States

Good Samaritan Hospital - Dayton, Dayton, United States

Miami Valley Hospital, Dayton, United States

Samaritan North Health Center, Dayton, United States

Dayton CCOP, Dayton, United States

Grady Memorial Hospital, Delaware, United States

Blanchard Valley Hospital, Findlay, United States

Atrium Medical Center-Middletown Regional Hospital, Franklin, United States

Wayne Hospital, Greenville, United States

Kettering Medical Center, Kettering, United States

Fairfield Medical Center, Lancaster, United States

Saint Rita's Medical Center, Lima, United States

Marietta Memorial Hospital, Marietta, United States

Hillcrest Hospital Cancer Center, Mayfield Heights, United States

Lake University Ireland Cancer Center, Mentor, United States

Knox Community Hospital, Mount Vernon, United States

Licking Memorial Hospital, Newark, United States

Southern Ohio Medical Center, Portsmouth, United States

Springfield Regional Medical Center, Springfield, United States

Upper Valley Medical Center, Troy, United States

Saint Ann's Hospital, Westerville, United States

Clinton Memorial Hospital, Wilmington, United States

Greene Memorial Hospital, Xenia, United States

Genesis HealthCare System, Zanesville, United States

University of Oklahoma Health Sciences Center, Oklahoma City, United States

Tulsa Cancer Institute, Tulsa, United States

Abington Memorial Hospital, Abington, United States

Lehigh Valley Hospital-Cedar Crest, Allentown, United States

Saint Luke's University Hospital-Bethlehem Campus, Bethlehem, United States

Bryn Mawr Hospital, Bryn Mawr, United States

Penn State Milton S Hershey Medical Center, Hershey, United States

Paoli Memorial Hospital, Paoli, United States

Pennsylvania Hospital, Philadelphia, United States

Fox Chase Cancer Center, Philadelphia, United States

Temple University Hospital, Philadelphia, United States

UPMC-Magee Womens Hospital, Pittsburgh, United States

West Penn Hospital, Pittsburgh, United States

Reading Hospital, West Reading, United States

Lankenau Medical Center, Wynnewood, United States

Mainline Health CCOP, Wynnewood, United States

Women and Infants Hospital, Providence, United States

AnMed Health Cancer Center, Anderson, United States

AnMed Health Hospital, Anderson, United States

Medical University of South Carolina, Charleston, United States

South Carolina Oncology Associates PA, Columbia, United States

Greenville Health System Cancer Institute-Easley, Easley, United States

McLeod Regional Medical Center, Florence, United States

Saint Francis Hospital, Greenville, United States

Greenville Health System Cancer Institute-Andrews, Greenville, United States

Greenville Health System Cancer Institute-Butternut, Greenville, United States

Greenville Health System Cancer Institute-Faris, Greenville, United States

Greenville Memorial Hospital, Greenville, United States

Greenville Health System Cancer Institute-Eastside, Greenville, United States

Self Regional Healthcare, Greenwood, United States

Cancer Centers of the Carolinas-Greer Medical Oncology, Greer, United States

Greenville Health System Cancer Institute-Greer, Greer, United States

Greenville Health System Cancer Institute-Seneca, Seneca, United States

Spartanburg Medical Center, Spartanburg, United States

Upstate Carolina CCOP, Spartanburg, United States

Greenville Health System Cancer Institute-Spartanburg, Spartanburg, United States

Black Hills Obstetrics and Gynecology, Rapid City, United States

Sanford Cancer Center-Oncology Clinic, Sioux Falls, United States

Avera Cancer Institute, Sioux Falls, United States

Medical X-Ray Center, Sioux Falls, United States

Sanford USD Medical Center - Sioux Falls, Sioux Falls, United States

Wellmont Holston Valley Hospital and Medical Center, Kingsport, United States

University of Tennessee - Knoxville, Knoxville, United States

Tennessee Oncology PLLC- Centennial Medical Center, Nashville, United States

Meharry Medical College, Nashville, United States

Vanderbilt University/Ingram Cancer Center, Nashville, United States

University Medical Center Brackenridge, Austin, United States

Parkland Memorial Hospital, Dallas, United States

Zale Lipshy University Hospital, Dallas, United States

Clements University Hospital, Dallas, United States

UT Southwestern/Simmons Cancer Center-Dallas, Dallas, United States

Brooke Army Medical Center, Fort Sam Houston, United States

Baylor All Saints Medical Center at Fort Worth, Fort Worth, United States

University of Texas Medical Branch at Galveston, Galveston, United States

Lyndon Baines Johnson General Hospital, Houston, United States

Baylor College of Medicine, Houston, United States

Ben Taub General Hospital, Houston, United States

M D Anderson Cancer Center, Houston, United States

Methodist Hospital, Houston, United States

Saint Luke's Episcopal Hospital, Houston, United States

Veterans Administration Medical Center, Houston, United States

Wilford Hall Medical Center, Lackland Air Force Base, United States

Scott and White Memorial Hospital, Temple, United States

American Fork Hospital, American Fork, United States

Sandra L Maxwell Cancer Center, Cedar City, United States

Logan Regional Hospital, Logan, United States

Intermountain Medical Center, Murray, United States

McKay-Dee Hospital Center, Ogden, United States

Utah Valley Regional Medical Center, Provo, United States

Intermountain Health Care, Salt Lake City, United States

Utah Cancer Specialists-Salt Lake City, Salt Lake City, United States

Huntsman Cancer Institute/University of Utah, Salt Lake City, United States

LDS Hospital, Salt Lake City, United States

Dixie Medical Center Regional Cancer Center, St. George, United States

Fletcher Allen Health Care-Medical Center, Burlington, United States

University of Virginia, Charlottesville, United States

Southwest VA Regional Cancer Center, Norton, United States

Virginia Commonwealth University/Massey Cancer Center, Richmond, United States

Carilion Clinic Gynecological Oncology, Roanoke, United States

Providence Regional Cancer System-Centralia, Centralia, United States

Saint Francis Hospital, Federal Way, United States

Saint Clare Hospital, Lakewood, United States

Providence - Saint Peter Hospital, Olympia, United States

MultiCare Good Samaritan Hospital, Puyallup, United States

MultiCare Allenmore Hospital, Tacoma, United States

Northwest CCOP, Tacoma, United States

Saint Joseph Medical Center, Tacoma, United States

Multicare Health System, Tacoma, United States

Langlade Hospital and Cancer Center, Antigo, United States

Marshfield Clinic-Chippewa Center, Chippewa Falls, United States

Marshfield Clinic Cancer Center at Sacred Heart, Eau Claire, United States

Green Bay Oncology at Saint Vincent Hospital, Green Bay, United States

Saint Vincent Hospital, Green Bay, United States

Green Bay Oncology Limited at Saint Mary's Hospital, Green Bay, United States

Saint Mary's Hospital, Green Bay, United States

Gundersen Lutheran Medical Center, La Crosse, United States

University of Wisconsin Hospital and Clinics, Madison, United States

Holy Family Memorial Hospital, Manitowoc, United States

Bay Area Medical Center, Marinette, United States

Marshfield Clinic, Marshfield, United States

Saint Joseph's Hospital, Marshfield, United States

Aurora Saint Luke's Medical Center, Milwaukee, United States

Froedtert and the Medical College of Wisconsin, Milwaukee, United States

Aurora Sinai Medical Center, Milwaukee, United States

Marshfield Clinic-Minocqua Center, Minocqua, United States

D N Greenwald Center, Mukwonago, United States

Oconomowoc Memorial Hospital-ProHealth Care Inc, Oconomowoc, United States

Green Bay Oncology - Oconto Falls, Oconto Falls, United States

Marshfield Clinic at James Beck Cancer Center, Rhinelander, United States

Marshfield Clinic-Rice Lake Center, Rice Lake, United States

Marshfield Clinic Cancer Care at Saint Michael's Hospital, Stevens Point, United States

Saint Michael's Hospital, Stevens Point, United States

Green Bay Oncology - Sturgeon Bay, Sturgeon Bay, United States

Vince Lombardi Cancer Clinic, Two Rivers, United States

Waukesha Memorial Hospital, Waukesha, United States

Aspirus Regional Cancer Center, Wausau, United States

Aurora West Allis Medical Center, West Allis, United States

Marshfield Clinic - Weston Center, Weston, United States

Marshfield Clinic - Wisconsin Rapids Center, Wisconsin Rapids, United States

Rocky Mountain Oncology, Casper, United States

Welch Cancer Center, Sheridan, United States

Vall d'Hebron University Hospital, Barcelona, Spain

Hospital Reina Sofia, Córdoba, Spain

Hospital Universitari de Girona Doctor Josep Trueta, Girona, Spain

Hospital Universitario Gregorio Maranon, Madrid, Spain

M D Anderson International Spain, Madrid, Spain

Hospital Universitario La Paz, Madrid, Spain

Hospital Son Llatzer, Palma, Spain

Instituto Valenciano de Oncologia, Valencia, Spain

Linked Papers

2020-08-26

Circulating Tumor Cells In Advanced Cervical Cancer: NRG Oncology—Gynecologic Oncology Group Study 240 (NCT 00803062)

Abstract To isolate circulating tumor cells (CTC) from women with advanced cervical cancer and estimate the impact of CTCs and treatment on overall survival and progression-free survival (PFS). A total of 7.5 mL of whole blood was drawn pre-cycle 1 and 36 days post-cycle 1 from patients enrolled on Gynecologic Oncology Group 0240, the phase III randomized trial that led directly to regulatory approval of the antiangiogenesis drug, bevacizumab, in women with recurrent/metastatic cervical cancer. CTCs (defined as anti-cytokeratin+/anti-CD45− cells) were isolated from the buffy coat layer using an anti-EpCAM antibody-conjugated ferrofluid and rare earth magnet, and counted using a semiautomated fluorescence microscope. The median pre-cycle 1 CTC count was 7 CTCs/7.5 mL whole blood (range, 0–18) and, at 36 days posttreatment, was 4 (range, 0–17). The greater the declination in CTCs between time points studied, the lower the risk of death [HR, 0.87; 95% confidence interval (CI), 0.79–0.95)]. Among patients with high (≥ median) pretreatment CTCs, bevacizumab treatment was associated with a reduction in the hazard of death (HR, 0.57; 95% CI, 0.32–1.03) and PFS (HR, 0.59; 95% CI, 0.36–0.96). This effect was not observed with low (&amp;lt; median) CTCs. CTCs can be isolated from women with advanced cervical cancer and may have prognostic significance. A survival benefit conferred by bevacizumab among patients with high pretreatment CTCs may reflect increased tumor neovascularization and concomitant vulnerability to VEGF inhibition. These data support studying CTC capture as a potential predictive biomarker.

Linked Investigators

Ana Oaknin

Dr. Ana Oaknin is the Head of the Gynaecological Cancer Programme at the Vall d’Hebron Institute of Oncology (VHIO) in Barcelona, Spain and a prominent figure in the field of Gynaecological Oncology, internationally. Dr. Oaknin is an active faculty member of the European Society of Medical Oncology (ESMO) Gynaecologic Track. She has served as Scientific Commit Member for ESMO Meeting in the last few years, as Subject Editor for Gynaecologic Malignancies Guidelines (2022-2024)and she is chair of the ESMO gynaecological cancer congress (2024-2026). Dr. Oaknin has been the Gynaecologic Cancer Intergroup (GCIG) Cervical Cancer Committee Chair from 2022-2224 and is an active member of American Society of Clinical Oncology (ASCO), Society of Gynaecologic Oncology (SGO) where she serves as International Member on the Board Committee. Dr. Oaknin obtained her degree in Medicine and Surgery from the Complutense University of Madrid in 1994 and specialized in Medical Oncology at the Hospital Universitario de la Princesa, Universidad Complutense de Madrid, becoming board certified in 2000. She earned her PhD Cum Laude from the Universidad Autónoma de Barcelona in 2016. Throughout her career, Dr Oaknin has been primarily focused on clinical research, serving as the principal investigator for numerous Phase I, II, and III studies, both nationally and internationally. She is the author of many outstanding articles in high impact journals.

Debra L Richardson

Eric L. Eisenhauer

Linda Van Le