Carboplatin and Paclitaxel or Oxaliplatin and Capecitabine With or Without Bevacizumab as First-Line Therapy in Treating Patients With Newly Diagnosed Stage II-IV or Recurrent Stage I Epithelial Ovarian or Fallopian Tube Cancer

Recurrent Ovarian Carcinoma Clinical Trial

Official title:

A GCIG Intergroup Multicenter Phase III Trial of Open Label Carboplatin and Paclitaxel +/- NCI-Supplied Agent: Bevacizumab (NSC #704865) Compared With Oxaliplatin and Capecitabine +/- Bevacizumab as First Line Chemotherapy in Patients With Mucinous Epithelial Ovarian or Fallopian Tube Cancer (MEOC)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01081262
• Other study ID #: NCI-2011-02516
• Secondary ID: NCI-2011-02516GO
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 12, 2010
• Est. completion date: March 1, 2025

Study information

• Verified date: March 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase III trial studies carboplatin given together with paclitaxel with or without bevacizumab to see how well it works compared with oxaliplatin given together with capecitabine with or without bevacizumab as first-line therapy in treating patients with newly diagnosed stage II-IV, or recurrent (has come back) stage I epithelial ovarian or fallopian tube cancer. Drugs used in chemotherapy, such as carboplatin, paclitaxel, oxaliplatin, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, may block tumor growth in different ways by targeting certain cells. It is not yet known which regimen of combination chemotherapy given together with or without bevacizumab is more effective in treating epithelial ovarian cancer or fallopian tube cancer.

Description:

PRIMARY OBJECTIVES: I. To determine if capecitabine and oxaliplatin reduces the death rate compared to carboplatin and paclitaxel in women with mucinous adenocarcinoma of the ovary or fallopian tube. II. To determine if bevacizumab reduces the death rate compared to no bevacizumab in women with mucinous adenocarcinoma of the ovary or fallopian tube. SECONDARY OBJECTIVES: I. To determine if capecitabine and oxaliplatin increases the duration of progression-free survival (PFS) compared to carboplatin and paclitaxel in women with mucinous adenocarcinoma of the ovary or fallopian tube. II. To determine if bevacizumab increases the duration of PFS compared to no bevacizumab in women with mucinous adenocarcinoma of the ovary or fallopian tube. III. To compare the response rates for capecitabine and oxaliplatin versus carboplatin and paclitaxel in patients with mucinous adenocarcinoma of the ovary or fallopian tube with measurable disease after initial tumor reductive surgery. IV. To compare the response rates for bevacizumab versus no bevacizumab in patients with mucinous adenocarcinoma of the ovary or fallopian tube with measurable disease after initial tumor reductive surgery. V. To determine the nature and degree of toxicity of capecitabine and oxaliplatin compared with that of carboplatin and paclitaxel in this cohort of patients. VI. To determine the nature and degree of toxicity of bevacizumab in this cohort of patients. VII. To compare capecitabine and oxaliplatin versus carboplatin and paclitaxel with respect to changes in patient reported neurotoxicity. VIII. To determine the impact on quality of life (QOL, as measured by the Functional Assessment of Cancer Therapy-Ovarian [FACT-O] Trial Outcome Index [TOI]) following treatment with the above regimens. TERTIARY OBJECTIVES: I. To collect fixed and/or frozen tissue and whole blood for future research studies. OUTLINE: Patients are randomized to 1 of 4 treatment arms. ARM I: Patients receive carboplatin intravenously (IV) over 30-60 minutes on day 1 and paclitaxel IV over 3 hours on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive oxaliplatin IV over 2-6 hours on day 1 and capecitabine orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. ARM III: Patients receive carboplatin and paclitaxel IV as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes alone on day 1. Treatment repeats every 3 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. ARM IV: Patients receive oxaliplatin and capecitabine as in arm II, and bevacizumab as in arm III. After completion of study treatment, patients are followed up at 4-6 weeks, every 3 months for 2 years, and then every 6 months for 3 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: March 1, 2025
• Est. primary completion date: February 25, 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with a histologic diagnosis of mucinous adenocarcinoma of the ovary or fallopian tube with either optimal (=< 1 cm residual disease) or suboptimal residual disease following initial surgery; patients may have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or no measurable disease
• All patients must have had appropriate surgery including appendectomy (unless patient has history of prior appendectomy) for ovarian or fallopian tube carcinoma with appropriate tissue available for histologic evaluation to confirm diagnosis and stage
• Patients must have stage II-IV disease (new or recurrent-chemonaïve; no brain metastasis) or recurrent stage I disease (chemonaïve)
• Newly diagnosed patients must begin protocol therapy within 10 weeks of primary debulking; for stage I recurrent patients (chemonaïve), they should begin protocol therapy within 14 days of randomization
• Patients must have a negative colonoscopy within 1 year of enrolling in the study
• Absolute neutrophil count (ANC) >= 1,500/mcl
• White blood cell (WBC) count >= 3,000/mcl
• Platelets >= 100,000/mcl
• Hemoglobin (Hgb) >= 10 g/dl (can be post transfusion)
• Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN) OR creatinine clearance > 50 cc/min
• Bilirubin =< 1.5 x ULN
• Serum glutamic oxaloacetic transaminase (SGOT) =< to 2.5 x ULN
• Alkaline phosphatase =< to 2.5 x ULN
• Neuropathy (sensory and motor) =< Common Terminology Criteria for Adverse Events (CTCAE) grade 1
• Urine dipstick for proteinuria < 2+; if urine dipstick is >= 2+, 24 hour urine must demonstrate =< 1 g protein in 24 hours OR patients must have a urine protein-to-creatinine ratio (UPCR) < 1.0 mg/dL
• Prothrombin time (PT) =< 1.5 x ULN
• Activated prothrombin time (APTT) =< 1.5 x ULN
• Patients of childbearing potential must agree to practice an effective form of birth control during study treatment and for six months after completion of treatment
• Patients who have met the pre-entry requirements
• Patients must have signed an approved informed consent and authorization permitting release of personal health information
• Patients with Gynecologic Oncology Group (GOG) performance grade of 0, 1 or 2
• Patients with life expectancy > 3 months

Exclusion Criteria:

• Patients with known colon cancer or history of colon cancer
• Patients with primary peritoneal carcinoma
• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last 5 years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
• Patients who have received chemotherapy, radiotherapy or any investigational treatment for a gynecologic cancer (does include breast cancer) or colorectal cancer prior to enrollment
• Patients with a major surgical procedure anticipated during the course of the study; this includes but is not limited to: abdominal surgery (laparotomy or laparoscopy) 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
• Patients may have minor surgical procedures (i.e., mediport insertion) fine needle aspiration or core biopsies as long as it is performed > 7 days prior to the first date of bevacizumab therapy and there is no evidence of wound disruption or impaired healing
• Patients with surgery (including open biopsy) within 4 weeks prior to anticipated first dose of bevacizumab (allowing for fact that bevacizumab can be omitted from first cycle of chemotherapy)
• Patients with a history of abdominal fistula or perforation within the past 12 months
• Patients with a current, serious, non-healing wound, ulcer, or bone fracture; 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 known hypersensitivity to Chinese hamster cell products or other recombinant human or humanized antibodies
• Patients with mixed epithelial ovarian cancer histology
• Patients with tumors of low malignant potential
• History or evidence of upon physical examination of central nervous system (CNS) disease, including history of primary brain tumor or any history of brain metastases, or seizures not controlled with standard medical therapy
• Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 100 mm Hg; patients with a history of hypertension are permitted
• Myocardial infarction or unstable angina within 12 months of the first date of bevacizumab therapy
• New York Heart Association (NYHA) grade II or greater congestive heart failure or serious cardiac arrhythmia requiring medication; women who have received prior treatment with anthracycline (including doxorubicin and/or liposomal doxorubicin) and have an ejection fraction < 50% will be excluded from the study
• Grade 1, category 2 or greater, peripheral vascular disease; patient cannot have anything worse than mild, symptomatic claudication with exercise
• History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of bevacizumab therapy
• History of pulmonary embolism or deep vein thrombosis in the past 6 months
• Previous history of malabsorption or other conditions preventing oral treatment
• Patients who are pregnant or nursing
• Patients with acute hepatitis or active infection that requires parenteral antibiotics
• Patients with active bleeding or pathologic conditions that carry a high risk of bleeding such as a known bleeding disorder, coagulopathy or tumor involving the major vessels
• Patients taking warfarin

Related Conditions & MeSH terms

• Borderline Ovarian Mucinous Tumor
• Carcinoma
• Carcinoma, Ovarian Epithelial
• Cystadenocarcinoma
• Fallopian Tube Neoplasms
• Ovarian Mucinous Cystadenocarcinoma
• Ovarian Neoplasms
• Recurrence
• Recurrent Fallopian Tube Carcinoma
• Recurrent Ovarian Carcinoma
• Stage IA Fallopian Tube Cancer AJCC v6 and v7
• Stage IA Ovarian Cancer AJCC v6 and v7
• Stage IB Fallopian Tube Cancer AJCC v6 and v7
• Stage IB Ovarian Cancer AJCC v6 and v7
• Stage IC Fallopian Tube Cancer AJCC v6 and v7
• Stage IC Ovarian Cancer AJCC v6 and v7
• Stage IIA Fallopian Tube Cancer AJCC v6 and v7
• Stage IIA Ovarian Cancer AJCC V6 and v7
• Stage IIB Fallopian Tube Cancer AJCC v6 and v7
• Stage IIB Ovarian Cancer AJCC v6 and v7
• Stage IIC Fallopian Tube Cancer AJCC v6 and v7
• Stage IIC Ovarian Cancer AJCC v6 and v7
• Stage IIIA Fallopian Tube Cancer AJCC v7
• Stage IIIA Ovarian Cancer AJCC v6 and v7
• Stage IIIB Fallopian Tube Cancer AJCC v7
• Stage IIIB Ovarian Cancer AJCC v6 and v7
• Stage IIIC Fallopian Tube Cancer AJCC v7
• Stage IIIC Ovarian Cancer AJCC v6 and v7
• Stage IV Fallopian Tube Cancer AJCC v6 and v7
• Stage IV Ovarian Cancer AJCC v6 and v7

Intervention

Biological:
• Bevacizumab
Given IV

Drug:
• Capecitabine
Given PO
• Carboplatin
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Oxaliplatin
Given IV
• Paclitaxel
Given IV

Other:
• Quality-of-Life Assessment
Ancillary studies

Locations

Country	Name	City	State
United States	Jefferson Abington Hospital	Abington	Pennsylvania
United States	Summa Health System - Akron Campus	Akron	Ohio
United States	Southwest Gynecologic Oncology Associates Inc	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	AnMed Health Hospital	Anderson	South Carolina
United States	Augusta University Medical Center	Augusta	Georgia
United States	The Medical Center of Aurora	Aurora	Colorado
United States	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Mary Rutan Hospital	Bellefontaine	Ohio
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	Saint Vincent Frontier Cancer Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Mid Dakota Clinic	Bismarck	North Dakota
United States	Saint Alexius Medical Center	Bismarck	North Dakota
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Boulder Community Hospital	Boulder	Colorado
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Aultman Health Foundation	Canton	Ohio
United States	Graham Hospital Association	Canton	Illinois
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	East Bay Radiation Oncology Center	Castro Valley	California
United States	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Columbus NCI Community Oncology Research Program	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	John B Amos Cancer Center	Columbus	Georgia
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Danville Regional Medical Center	Danville	Virginia
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Heartland Cancer Research NCORP	Decatur	Illinois
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	Western States Cancer Research NCORP	Denver	Colorado
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Duke University Medical Center	Durham	North Carolina
United States	Saint Elizabeth Healthcare Edgewood	Edgewood	Kentucky
United States	Elkhart Clinic	Elkhart	Indiana
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana
United States	Christiana Care - Union Hospital	Elkton	Maryland
United States	Bay Area Breast Surgeons Inc	Emeryville	California
United States	Epic Care Partners in Cancer Care	Emeryville	California
United States	Swedish Medical Center	Englewood	Colorado
United States	Green Bay Oncology - Escanaba	Escanaba	Michigan
United States	Eureka Hospital	Eureka	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Hematology Oncology Associates of Fredericksburg Inc	Fredericksburg	Virginia
United States	Valley Medical Oncology Consultants-Fremont	Fremont	California
United States	Northeast Georgia Medical Center-Gainesville	Gainesville	Georgia
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	University of Texas Medical Branch	Galveston	Texas
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Hartford Hospital	Hartford	Connecticut
United States	Illinois CancerCare-Havana	Havana	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Northern Montana Hospital	Havre	Montana
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Saint Peter's Community Hospital	Helena	Montana
United States	AdventHealth Hendersonville	Hendersonville	North Carolina
United States	Sudarshan K Sharma MD Limited-Gynecologic Oncology	Hinsdale	Illinois
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	Houston Methodist Hospital	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Memorial Hermann Texas Medical Center	Houston	Texas
United States	Ascension Saint Vincent Indianapolis Hospital	Indianapolis	Indiana
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro	Jonesboro	Arkansas
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Glacier Oncology PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	University of Tennessee - Knoxville	Knoxville	Tennessee
United States	Community Howard Regional Health	Kokomo	Indiana
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	IU Health La Porte Hospital	La Porte	Indiana
United States	Cancer Center of Acadiana	Lafayette	Louisiana
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Women's Cancer Center of Nevada	Las Vegas	Nevada
United States	Beebe Medical Center	Lewes	Delaware
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	Los Angeles General Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	McKee Medical Center	Loveland	Colorado
United States	Centra Lynchburg Hematology-Oncology Clinic Inc	Lynchburg	Virginia
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Mcdonough District Hospital	Macomb	Illinois
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	Contra Costa Regional Medical Center	Martinez	California
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Cancer Care Partners LLC	Mishawaka	Indiana
United States	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana
United States	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana
United States	Montana Cancer Specialists	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama
United States	Holy Family Medical Center	Monmouth	Illinois
United States	Illinois CancerCare-Monmouth	Monmouth	Illinois
United States	Virtua Memorial	Mount Holly	New Jersey
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	El Camino Hospital	Mountain View	California
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Licking Memorial Hospital	Newark	Ohio
United States	Corewell Health Lakeland Hospitals - Niles Hospital	Niles	Michigan
United States	Bromenn Regional Medical Center	Normal	Illinois
United States	Carle Cancer Institute Normal	Normal	Illinois
United States	Illinois CancerCare-Community Cancer Center	Normal	Illinois
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Tumor Institute	Oakland	California
United States	Hematology and Oncology Associates-Oakland	Oakland	California
United States	Highland General Hospital	Oakland	California
United States	Tom K Lee Inc	Oakland	California
United States	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	AdventHealth Orlando	Orlando	Florida
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Parker Adventist Hospital	Parker	Colorado
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Illinois Valley Hospital	Peru	Illinois
United States	Saint Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Pikeville Medical Center	Pikeville	Kentucky
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Swedish American Hospital	Rockford	Illinois
United States	Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	South Bend Clinic	South Bend	Indiana
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Illinois CancerCare-Spring Valley	Spring Valley	Illinois
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Stamford Hospital/Bennett Cancer Center	Stamford	Connecticut
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	Olive View-University of California Los Angeles Medical Center	Sylmar	California
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	North Suburban Medical Center	Thornton	Colorado
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Virtua Voorhees	Voorhees	New Jersey
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Michiana Hematology Oncology PC-Westville	Westville	Indiana
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Southeast Clinical Oncology Research Consortium NCORP	Winston-Salem	North Carolina
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Numbers and Percentages of Patients With Mutations in the Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Oncogene	Will be tabulated. Interactions between the mutational status of the KRAS oncogene and treatment will be examined.	Baseline
Primary	Overall Survival	Overall survival is defined as the duration of time from study entry to time of death, or the date of last contact.	Up to five years
Secondary	Participants With Grade 1 or Higher Non-serious Adverse Effects Assessed by CTCAE Version 4.0	Grade 1 or higher non-serious adverse events were graded by CTC AE v 4.	Every cycle while on treatment, up to 5 years
Secondary	Progression-free Survival	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, or a measurable increase in a non-target lesion, or the appearance of new lesions.	Is measured from date of randomization until first indication of progression based on RECIST criteria or death from any cause, or if progression-free at last contact, the date of last disease assessment up to 10 years.
Secondary	Objective Tumor Response	Complete and Partial Tumor Response by RECIST 1.1. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v.1.1) 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; Overall response (OR) = CR + PR	CT scan or MRI if used to follow lesion for measurable disease every other cycle for the first 6 months; then every 3 months x 2; then every 6 months thereafter until disease progression, and any other time clinically indicated, up to 5 years
Secondary	Patient Reported Neurotoxicity	Patient reported neurotoxicity symptoms as measured with the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - neurotoxicity subscale (short version) (FACT/GOG-Ntx subscale). The FACT/GOG-Ntx subscale contains 4 items. Each item was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative items, reversal was performed prior to score calculation. According to the FACIT measurement system, the Ntx score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the scale. The Ntx score ranges 0-16 with a large score suggests less neurotoxicity.	baseline (pre-treatment), pre cycle 4, post cycle 6, six months post-chemo, end of bevacizumab [BEV] (or 39 weeks after completion of chemotherapy in the non-BEV arms or in those who discontinue BEV), six months after BEV, and years 2, 3, 4, and 5
Secondary	Patient Reported Quality of Life	Patient reported quality of life was measured with the Treatment Outcome Index of the Functional Assessment of Cancer Therapy for endometrial cancer (FACT-O TOI). The FACT-O TOI is a scale for assessing general QOL of ovarian cancer patients. It consists of three subscales: Physical Well Being (7 items), Functional Well Being (7 items), and Ovarian Cancer subscale (11 items). Each item in the FACT-O TOI was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative statements (or questions), reversal was performed prior to score calculation. According to the FACIT measurement system, a subscale score was the summation of the individual item scores if more than 50% of subscale items were answered. The FACT-O TOI score ranges 0-100 with a large score suggests better QOL	baseline (pre-treatment), pre cycle 4, post cycle 6, six months post-chemo, end of bevacizumab [BEV] (or 39 weeks after completion of chemotherapy in the non-BEV arms or in those who discontinue BEV), six months after BEV, and years 2, 3, 4, and 5