Carboplatin, Paclitaxel, and Bevacizumab With or Without Everolimus in Treating Patients With Metastatic Malignant Melanoma

A Randomized Phase II Trial of Carboplatin, Paclitaxel, Bevacizumab, With or Without Everolimus for Therapy of Metastatic Malignant Melanoma

This randomized phase II trial is studying how well carboplatin, paclitaxel, and bevacizumab work when given with or without everolimus in treating patients with malignant melanoma that has spread from where it started to other places in the body. Drugs used in chemotherapy, such as carboplatin and paclitaxel, 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 the ability of tumor cells to grow and spread. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether combination chemotherapy given together with bevacizumab is more effective with or without everolimus in treating patients with metastatic melanoma.

Study Overview

• Status: Completed
• Conditions: Melanoma (Skin)
• Intervention / Treatment: Biological: bevacizumab; Drug: paclitaxel; Drug: carboplatin; Drug: everolimus

Detailed Description

OBJECTIVES:

Primary

• To assess whether there is sufficient promise of an impact of the addition of everolimus to the combination of carboplatin, paclitaxel, and bevacizumab on progression-free survival that it would be recommended for further testing in patients with metastatic malignant melanoma.

Secondary

• To estimate the confirmed tumor response rate of each of the treatment regimens.
• To estimate the distribution of overall survival (OS) time for each of the treatment regimens.
• To assess the impact on the safety profile of the addition of everolimus to the combination of carboplatin, paclitaxel, and bevacizumab.

OUTLINE: This is a multicenter study. Patients are stratified according to elevated LDH (above upper limit of normal) at baseline (yes vs no), location of metastatic disease (M1a [skin, subcutaneous tissue, or lymph node only] vs M1b [lung] vs M1c [other visceral sites]) and prior chemotherapy for metastatic disease (yes vs no). Patients are randomized to 1 of 2 treatment arms.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15, paclitaxel IV over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive bevacizumab, paclitaxel, and carboplatin as in Arm I. Patients also receive everolimus orally (PO) once daily (QD) 3 times weekly. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3-6 months for up to 5 years.

• Study Type: Interventional
• Enrollment (Actual): 149
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5499
      • Mayo Clinic Scottsdale
  • California
    • Martinez, California, United States, 94553-3156
      • Contra Costa Regional Medical Center
    • Mountain View, California, United States, 94040
      • El Camino Hospital Cancer Center
    • Oakland, California, United States, 94609
      • Larry G Strieff MD Medical Corporation
    • Oakland, California, United States, 94609
      • CCOP - Bay Area Tumor Institute
    • Oakland, California, United States, 94609
      • Bay Area Breast Surgeons, Incorporated
    • Oakland, California, United States, 94609
      • Tom K Lee, Incorporated
    • San Pablo, California, United States, 94806
      • Doctors Medical Center - San Pablo Campus
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Aurora Presbyterian Hospital
    • Boulder, Colorado, United States, 80301-9019
      • Boulder Community Hospital
    • Colorado Springs, Colorado, United States, 80933
      • Penrose Cancer Center at Penrose Hospital
    • Denver, Colorado, United States, 80210
      • Porter Adventist Hospital
    • Denver, Colorado, United States, 80220
      • Rose Medical Center
    • Denver, Colorado, United States, 80218
      • Presbyterian - St. Luke's Medical Center
    • Denver, Colorado, United States, 80204
      • St. Anthony Central Hospital
    • Denver, Colorado, United States, 80218
      • St. Joseph Hospital
    • Englewood, Colorado, United States, 80110
      • Swedish Medical Center
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Hospital
    • Fort Collins, Colorado, United States, 80528
      • Front Range Cancer Specialists
    • Greeley, Colorado, United States, 80631
      • North Colorado Medical Center
    • Lone Tree, Colorado, United States, 80124
      • Sky Ridge Medical Center
    • Longmont, Colorado, United States, 80501
      • Hope Cancer Care Center at Longmont United Hospital
    • Loveland, Colorado, United States, 80539
      • McKee Medical Center
    • Pueblo, Colorado, United States, 81004
      • St. Mary - Corwin Regional Medical Center
    • Thornton, Colorado, United States, 80229
      • North Suburban Medical Center
    • Wheat Ridge, Colorado, United States, 80033
      • Exempla Lutheran Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
    • Jacksonville, Florida, United States, 32207
      • Baptist Cancer Institute - Jacksonville
    • Jupiter, Florida, United States, 33458
      • Ella Milbank Foshay Cancer Center at Jupiter Medical Center
    • Lakeland, Florida, United States, 33805
      • Lakeland Regional Cancer Center at Lakeland Regional Medical Center
    • Miami Beach, Florida, United States, 33140
      • CCOP - Mount Sinai Medical Center
  • Georgia
    • Columbus, Georgia, United States, 31904
      • John B. Amos Cancer Center
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
  • Illinois
    • Aurora, Illinois, United States, 60504
      • Rush-Copley Cancer Care Center
    • Bloomington, Illinois, United States, 61701
      • Illinois CancerCare - Bloomington
    • Bloomington, Illinois, United States, 61701
      • St. Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare - Canton
    • Carthage, Illinois, United States, 62321
      • Illinois CancerCare - Carthage
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare - Eureka
    • Eureka, Illinois, United States, 61530
      • Eureka Community Hospital
    • Galesburg, Illinois, United States, 61401
      • Galesburg Clinic, PC
    • Havana, Illinois, United States, 62644
      • Illinois CancerCare - Havana
    • Kewanee, Illinois, United States, 61443
      • Illinois CancerCare - Kewanee Clinic
    • La Grange, Illinois, United States, 60525
      • La Grange Memorial Hospital
    • Macomb, Illinois, United States, 61455
      • Illinois CancerCare - Macomb
    • Moline, Illinois, United States, 61265
    • Moline, Illinois, United States, 61265
      • Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
    • Monmouth, Illinois, United States, 61462
      • Illinois CancerCare - Monmouth
    • Monmouth, Illinois, United States, 61462
      • OSF Holy Family Medical Center
    • Normal, Illinois, United States, 61761
      • Bromenn Regional Medical Center
    • Normal, Illinois, United States, 61761
      • Community Cancer Center
    • Normal, Illinois, United States, 61761
      • Illinois CancerCare - Community Cancer Center
    • Ottawa, Illinois, United States, 61350
      • Community Hospital of Ottawa
    • Ottawa, Illinois, United States, 61350
      • Oncology Hematology Associates of Central Illinois, PC - Ottawa
    • Pekin, Illinois, United States, 61554
      • Cancer Treatment Center at Pekin Hospital
    • Pekin, Illinois, United States, 61603
      • Illinois CancerCare - Pekin
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61614
      • Proctor Hospital
    • Peoria, Illinois, United States, 61637
      • OSF St. Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • CCOP - Illinois Oncology Research Association
    • Peoria, Illinois, United States, 61615
      • Oncology Hematology Associates of Central Illinois, PC - Peoria
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare - Peru
    • Peru, Illinois, United States, 61354
      • Illinois Valley Community Hospital
    • Princeton, Illinois, United States, 61356
      • Illinois CancerCare - Princeton
    • Spring Valley, Illinois, United States, 61362
      • Illinois CancerCare - Spring Valley
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Elkhart, Indiana, United States, 46514-2098
      • Elkhart Clinic, LLC
    • Elkhart, Indiana, United States, 46514
      • Michiana Hematology-Oncology, PC - Elkhart
    • Indianapolis, Indiana, United States, 46237
      • St. Francis Hospital Cancer Care Services
    • Kokomo, Indiana, United States, 46904
      • Howard Community Hospital
    • La Porte, Indiana, United States, 46350
      • Center for Cancer Therapy at LaPorte Hospital and Health Services
    • Michigan City, Indiana, United States, 46360
      • Saint Anthony Memorial Health Centers
    • Mishawaka, Indiana, United States, 46545-1470
      • Michiana Hematology-Oncology, PC - South Bend
    • Mishawaka, Indiana, United States, 46545-1470
      • Saint Joseph Regional Medical Center
    • Plymouth, Indiana, United States, 46563
      • Michiana Hematology Oncology PC - Plymouth
    • Richmond, Indiana, United States, 47374
      • Reid Hospital & Health Care Services
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46601
      • CCOP - Northern Indiana CR Consortium
    • Westville, Indiana, United States, 46391
      • Michiana Hematology Oncology PC - La Porte
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic, PC
    • Bettendorf, Iowa, United States, 52722
    • Cedar Rapids, Iowa, United States, 52403
      • Cedar Rapids Oncology Associates
    • Cedar Rapids, Iowa, United States, 52403
      • Mercy Regional Cancer Center at Mercy Medical Center
    • Clive, Iowa, United States, 50325
      • Medical Oncology and Hematology Associates - West Des Moines
    • Clive, Iowa, United States, 50325
      • Mercy Cancer Center - West Lakes
    • Des Moines, Iowa, United States, 50309
      • CCOP - Iowa Oncology Research Association
    • Des Moines, Iowa, United States, 50309
      • John Stoddard Cancer Center at Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates at John Stoddard Cancer Center
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates at Mercy Cancer Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Cancer Center at Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50316
      • John Stoddard Cancer Center at Iowa Lutheran Hospital
    • Iowa City, Iowa, United States, 52242-1002
      • Holden Comprehensive Cancer Center at University of Iowa
    • Mason City, Iowa, United States, 50401
      • Mercy Cancer Center at Mercy Medical Center - North Iowa
    • Ottumwa, Iowa, United States, 52501
      • McCreery Cancer Center at Ottumwa Regional
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology-Oncology Associates, LLP
    • Sioux City, Iowa, United States, 51102
      • Mercy Medical Center - Sioux City
    • Sioux City, Iowa, United States, 51104
      • St. Luke's Regional Medical Center
    • West Des Moines, Iowa, United States, 50266-7700
      • Methodist West Hospital
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas, PA - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas, PA - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - El Dorado
    • Fort Scott, Kansas, United States, 66701
      • Cancer Center of Kansas - Fort Scott
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas, PA - Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Liberal, Kansas, United States, 67901
      • Cancer Center of Kansas, PA - Liberal
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas, PA - Newton
    • Overland Park, Kansas, United States, 66209
      • Menorah Medical Center
    • Overland Park, Kansas, United States, 66213
      • Saint Luke's Hospital - South
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas, PA - Parsons
    • Prairie Village, Kansas, United States, 66208
      • CCOP - Kansas City
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas, PA - Pratt
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas, PA - Salina
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas, PA - Wellington
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas, PA - Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas, PA - Wichita
    • Wichita, Kansas, United States, 67214
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67214
      • Via Christi Cancer Center at Via Christi Regional Medical Center
    • Wichita, Kansas, United States, 67208
      • Associates in Womens Health, PA - North Review
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas, PA - Winfield
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University Cancer Research Center
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center at Bixby Medical Center
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Michigan Cancer Research Consortium
    • Battle Creek, Michigan, United States, 49017
      • Battle Creek Health System Cancer Care Center
    • Big Rapids, Michigan, United States, 49307
      • Mecosta County Medical Center
    • Dearborn, Michigan, United States, 48123-2500
      • Oakwood Cancer Center at Oakwood Hospital and Medical Center
    • Escanaba, Michigan, United States, 49431
      • Green Bay Oncology, Limited - Escanaba
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grand Rapids, Michigan, United States, 49503
      • Butterworth Hospital at Spectrum Health
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids
    • Grand Rapids, Michigan, United States, 49503
      • Lacks Cancer Center at Saint Mary's Health Care
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
    • Iron Mountain, Michigan, United States, 49801
      • Dickinson County Healthcare System
    • Jackson, Michigan, United States, 49201
      • Foote Memorial Hospital
    • Lansing, Michigan, United States, 48912-1811
      • Sparrow Regional Cancer Center
    • Livonia, Michigan, United States, 48154
      • St. Mary Mercy Hospital
    • Monroe, Michigan, United States, 48162
      • Community Cancer Center of Monroe
    • Monroe, Michigan, United States, 48162
      • Mercy Memorial Hospital - Monroe
    • Muskegon, Michigan, United States, 49444
      • Mercy General Health Partners
    • Pontiac, Michigan, United States, 48341-2985
      • St. Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Mercy Regional Cancer Center at Mercy Hospital
    • Reed City, Michigan, United States, 49677
      • Spectrum Health Reed City Hospital
    • Saginaw, Michigan, United States, 48601
      • Seton Cancer Institute at Saint Mary's - Saginaw
    • Saint Joseph, Michigan, United States, 49085
      • Lakeside Cancer Specialists, PLLC
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Regional Cancer Care Center - St. Joseph
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Warren, Michigan, United States, 48093
      • St. John Macomb Hospital
  • Minnesota
    • Bemidji, Minnesota, United States, 56601
      • MeritCare Bemidji
    • Brainerd, Minnesota, United States, 56401
      • St. Joseph's Medical Center
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy and Unity Cancer Center at Mercy Hospital
    • Duluth, Minnesota, United States, 55805
      • CCOP - Duluth
    • Duluth, Minnesota, United States, 55805
      • Miller - Dwan Medical Center
    • Duluth, Minnesota, United States, 55805-1983
      • Essentia Health - Duluth Clinic
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Mercy and Unity Cancer Center at Unity Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Maplewood, Minnesota, United States, 55109
      • HealthEast Cancer Care at St. John's Hospital
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology - Maplewood
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center - Minneapolis
    • Robbinsdale, Minnesota, United States, 55422-2900
      • Humphrey Cancer Center at North Memorial Outpatient Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
    • Saint Cloud, Minnesota, United States, 56303
      • CentraCare Clinic - River Campus
    • Saint Cloud, Minnesota, United States, 56303
      • Coborn Cancer Center
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Cancer Center
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Shakopee, Minnesota, United States, 55379
      • St. Francis Cancer Center at St. Francis Medical Center
    • St. Paul, Minnesota, United States, 55101
      • Regions Hospital Cancer Care Center
    • Stillwater, Minnesota, United States, 55082
      • Lakeview Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Willmar Cancer Center at Rice Memorial Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology - Woodbury
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Southeast Cancer Center
    • Columbia, Missouri, United States, 65203
      • Ellis Fischel Cancer Center at University of Missouri - Columbia
    • Jefferson City, Missouri, United States, 65109
      • Goldschmidt Cancer Center
    • Kansas City, Missouri, United States, 64116
      • North Kansas City Hospital
    • Kansas City, Missouri, United States, 64132
      • Research Medical Center
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Cancer Institute at Saint Luke's Hospital
    • Kansas City, Missouri, United States, 64118
      • Heartland Hematology Oncology Associates, Incorporated
    • Lee's Summit, Missouri, United States, 64086
      • Saint Luke's East - Lee's Summit
    • Rolla, Missouri, United States, 65401
      • Mercy Clinic Cancer and Hematology - Rolla
    • Saint Joseph, Missouri, United States, 64507
      • Saint Joseph Oncology, Incorporated
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Cancer Center
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
    • Springfield, Missouri, United States, 65804
      • St. John's Regional Health Center
    • Springfield, Missouri, United States, 65807
      • Hulston Cancer Center at Cox Medical Center South
    • Springfield, Missouri, United States, 65804
      • CCOP - Cancer Research for the Ozarks
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Billings, Montana, United States, 59101
      • St. Vincent Healthcare Cancer Care Services
    • Billings, Montana, United States, 59107-7000
      • Billings Clinic - Downtown
    • Billings, Montana, United States, 59102
      • Hematology-Oncology Centers of the Northern Rockies - Billings
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Cancer Center
    • Butte, Montana, United States, 59701
      • St. James Healthcare Cancer Care
    • Great Falls, Montana, United States, 59405
      • Benefis Sletten Cancer Institute
    • Helena, Montana, United States, 59601
      • St. Peter's Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Missoula, Montana, United States, 59807-7877
      • Montana Cancer Specialists at Montana Cancer Center
    • Missoula, Montana, United States, 59807
      • Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Cancer Resource Center - Lincoln
    • Omaha, Nebraska, United States, 68106
      • CCOP - Missouri Valley Cancer Consortium
    • Omaha, Nebraska, United States, 68122
      • Immanuel Medical Center
    • Omaha, Nebraska, United States, 68124
      • Alegant Health Cancer Center at Bergan Mercy Medical Center
    • Omaha, Nebraska, United States, 68131-2197
      • Creighton University Medical Center
    • Omaha, Nebraska, United States, 68130
      • Lakeside Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Nevada Cancer Research Foundation
  • New York
    • Glens Falls, New York, United States, 12801
      • Charles R. Wood Cancer Center at Glens Falls Hospital
  • North Carolina
    • Asheboro, North Carolina, United States, 27203-5400
      • Randolph Hospital
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital, Incorporated
    • Greensboro, North Carolina, United States, 27403-1198
      • Moses Cone Regional Cancer Center at Wesley Long Community Hospital
    • Hendersonville, North Carolina, United States, 28791
      • Pardee Memorial Hospital
    • Kinston, North Carolina, United States, 28501
      • Kinston Medical Specialists
    • Pinehurst, North Carolina, United States, 28374
      • FirstHealth Moore Regional Community Hospital Comprehensive Cancer Center
    • Reidsville, North Carolina, United States, 27320
      • Annie Penn Cancer Center
    • Statesville, North Carolina, United States, 28677
      • Iredell Memorial Hospital
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Medcenter One Hospital Cancer Care Center
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic, PC
    • Bismarck, North Dakota, United States, 58502
      • St. Alexius Medical Center Cancer Center
    • Fargo, North Dakota, United States, 58102
      • MeritCare Broadway
    • Grand Forks, North Dakota, United States, 58201
      • Altru Cancer Center at Altru Hospital
  • Ohio
    • Bowling Green, Ohio, United States, 43402
      • Wood County Oncology Center
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Columbus, Ohio, United States, 43214-3998
      • Riverside Methodist Hospital Cancer Care
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health - West Hospital
    • Columbus, Ohio, United States, 43215
      • CCOP - Columbus
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center Cancer Care
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital at Ohio Health
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital
    • Dayton, Ohio, United States, 45409
      • David L. Rike Cancer Center at Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Cancer Care Center
    • Dayton, Ohio, United States, 45420
      • CCOP - Dayton
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Elyria, Ohio, United States, 44035
      • Community Cancer Center
    • Elyria, Ohio, United States, 44035
      • Hematology Oncology Center
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Medical Associates
    • Franklin, Ohio, United States, 45005-1066
      • Middletown Regional Hospital
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Kettering, Ohio, United States, 45429
      • Charles F. Kettering Memorial Hospital
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Lima, Ohio, United States, 45804
      • Lima Memorial Hospital
    • Marietta, Ohio, United States, 45750
      • Strecker Cancer Center at Marietta Memorial Hospital
    • Maumee, Ohio, United States, 43537-1839
      • Northwest Ohio Oncology Center
    • Mount Vernon, Ohio, United States, 43050
      • Knox Community Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Cancer Care Program at Licking Memorial Hospital
    • Oregon, Ohio, United States, 43616
      • St. Charles Mercy Hospital
    • Oregon, Ohio, United States, 43616
      • Toledo Clinic - Oregon
    • Portsmouth, Ohio, United States, 45662
      • Southern Ohio Medical Center Cancer Center
    • Springfield, Ohio, United States, 45505
      • Community Hospital of Springfield and Clark County
    • Sylvania, Ohio, United States, 43560
      • Flower Hospital Cancer Center
    • Tiffin, Ohio, United States, 44883
      • Mercy Hospital of Tiffin
    • Toledo, Ohio, United States, 43608
      • St. Vincent Mercy Medical Center
    • Toledo, Ohio, United States, 43606
      • Toledo Hospital
    • Toledo, Ohio, United States, 43614
      • Medical University of Ohio Cancer Center
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic, Incorporated - Main Clinic
    • Toledo, Ohio, United States, 43623
      • St. Anne Mercy Hospital
    • Troy, Ohio, United States, 45373-1300
      • UVMC Cancer Care Center at Upper Valley Medical Center
    • Wauseon, Ohio, United States, 43567
      • Fulton County Health Center
    • Westerville, Ohio, United States, 43081
      • Mount Carmel St. Ann's Cancer Center
    • Xenia, Ohio, United States, 45385
      • Ruth G. McMillan Cancer Center at Greene Memorial Hospital
    • Zanesville, Ohio, United States, 43701
      • Genesis - Good Samaritan Hospital
  • Oklahoma
    • Norman, Oklahoma, United States, 73071
      • Cancer Care Associates - Norman
    • Oklahoma City, Oklahoma, United States, 73120
      • Cancer Care Associates - Mercy Campus
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center at St. Francis Hospital
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18105
      • Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
    • Danville, Pennsylvania, United States, 17822-0001
      • Geisinger Cancer Institute at Geisinger Health
    • Hazleton, Pennsylvania, United States, 18201
      • Geisinger Hazleton Cancer Center
    • Sayre, Pennsylvania, United States, 18840
      • Guthrie Cancer Center at Guthrie Clinic Sayre
    • State College, Pennsylvania, United States, 16801
      • Geisinger Medical Group - Scenery Park
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital Cancer Center
    • Greenville, South Carolina, United States, 29605
      • Cancer Centers of the Carolinas - Faris Road
    • Greenville, South Carolina, United States, 29605
      • Cancer Centers of the Carolinas - Grove Commons
    • Greer, South Carolina, United States, 29650
      • Cancer Centers of the Carolinas - Greer Medical Oncology
    • Seneca, South Carolina, United States, 29672
      • Cancer Centers of the Carolinas - Seneca
    • Spartanburg, South Carolina, United States, 29307
      • Cancer Centers of the Carolinas - Spartanburg
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
    • Sioux Falls, South Dakota, United States, 57117-5039
      • Sanford Cancer Center at Sanford USD Medical Center
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center
    • Fredericksburg, Virginia, United States, 22401
      • Fredericksburg Oncology, Incorporated
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Mary Babb Randolph Cancer Center at West Virginia University Hospitals
  • Wisconsin
    • Eau Claire, Wisconsin, United States, 54701
      • Center for Cancer Treatment & Prevention at Sacred Heart Hospital
    • Eau Claire, Wisconsin, United States, 54701
      • Marshfield Clinic Cancer Care at Regional Cancer Center
    • Green Bay, Wisconsin, United States, 54307-3508
      • St. Vincent Hospital Regional Cancer Center
    • Green Bay, Wisconsin, United States, 54301-3526
      • Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
    • Green Bay, Wisconsin, United States, 54303
      • Green Bay Oncology, Limited at St. Mary's Hospital
    • Green Bay, Wisconsin, United States, 54303
      • St. Mary's Hospital Medical Center - Green Bay
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Center for Cancer and Blood
    • Manitowoc, Wisconsin, United States, 54221-1450
      • Holy Family Memorial Medical Center Cancer Care Center
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Cancer Care Center at Bay Area Medical Center
    • Marshfield, Wisconsin, United States, 54449
      • Saint Joseph's Hospital
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic - Marshfield Center
    • Minocqua, Wisconsin, United States, 54548
      • Marshfield Clinic - Lakeland Center
    • Oconto Falls, Wisconsin, United States, 54154
      • Green Bay Oncology, Limited - Oconto Falls
    • Rhinelander, Wisconsin, United States, 54501
      • Ministry Medical Group at Saint Mary's Hospital
    • Rice Lake, Wisconsin, United States, 54868
      • Marshfield Clinic - Indianhead Center
    • Sheboygan, Wisconsin, United States, 53081
      • St. Nicholas Hospital
    • Stevens Point, Wisconsin, United States, 54481
      • Marshfield Clinic at Saint Michael's Hospital
    • Stevens Point, Wisconsin, United States, 54481
      • Saint Michael's Hospital Cancer Center
    • Sturgeon Bay, Wisconsin, United States, 54235
      • Green Bay Oncology, Limited - Sturgeon Bay
    • Weston, Wisconsin, United States, 54476
      • Marshfield Clinic - Weston Center
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Marshfield Clinic - Wisconsin Rapids Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologic proof of stage IV malignant melanoma not amenable to surgery; (biopsy can be of locoregional disease in setting of clinically evident stage IV disease, but primary tumor alone will not qualify)
• At most one prior chemotherapy based regimen for metastatic melanoma (no prior taxane-based regimens allowed); note: prior adjuvant non-taxane based chemotherapy and/or adjuvant immunotherapy are allowed; no limit on the number of prior biologic, immunologic or targeted therapies
• Measurable disease defined as at least one lesion whose longest diameter can be accurately measured as >= 2.0 cm with chest x-ray, or as >= 1.0 cm with computed tomography (CT) scan, CT component of a positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI) scan; note: disease that is measurable by physical examination only is not eligible
• Life expectancy >= 4 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Absolute neutrophil count (ANC) >= 1500/mL
• Platelets (PLT) >= 100,000 x 10^9/L
• Hemoglobin (Hgb) >= 9 g/dL (patients may be transfused to meet this requirement)
• Total cholesterol =< 300 mg/dL and; (note: serum levels of cholesterol or triglycerides found to be elevated may be lowered with anti-lipid therapy, but must be documented to be below these levels prior to enrollment)
• Triglycerides =< 2.5 X upper limit of normal (ULN); (note: serum levels of cholesterol or triglycerides found to be elevated may be lowered with anti-lipid therapy, but must be documented to be below these levels prior to enrollment)
• Creatinine =< 1.5 x ULN
• Total bilirubin =< 1.5 mg/dL (exception: patients with documented Gilbert's syndrome are allowed to participate despite elevated bilirubin)
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2.5 x ULN
• Alkaline phosphatase =< 2.5 x ULN
• Urine protein:creatinine (UPC) ratio < 1.0 at screening OR
• Urine dipstick for proteinuria < 2+ (patients discovered to have >= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate =< 1 g of protein in 24 hours to be eligible)
• Negative pregnancy test done =< 7 days prior to registration/randomization, for women of childbearing potential only
• Ability to understand and the willingness to sign a written informed consent document
• Willing to return to a North Central Cancer Treatment Group (NCCTG) institution for follow-up
• Willing to provide mandatory blood samples for research purposes
• Willing to follow a diet low in fat and cholesterol while taking everolimus
• Willing to abstain from eating grapefruit or drinking grapefruit juice for the duration of the study

Exclusion Criteria

• Prior treatment with agents disrupting vascular endothelial growth factor (VEGF) activity (i.e., bevacizumab, VEGF-trap, anti-VEGF receptor [R] monoclonal antibody [Mab]) or targeting VEGFR (e.g. sunitinib, sorafenib)
• Prior treatment with an mTOR inhibitor for melanoma (sirolimus, temsirolimus, everolimus)
• Brain metastases per MRI or CT at any time prior to registration; note: patients that have had primary therapy for brain metastasis (i.e. surgical resection, whole brain radiation, or stereotactic radiation therapy [SRT] even if stable) are not eligible
• Other investigational agents =< 4 weeks prior to registration/randomization
• Chemotherapy treatment =< 3 weeks prior to registration/randomization
• Any biologic, immunologic or targeted therapy =< 2 weeks prior to registration/randomization
• Major surgical procedure, open biopsy, or significant traumatic injury =< 4 weeks prior to registration/randomization
• Fine needle aspirations or core biopsies =< 7 days prior to registration/randomization
• Planned/or anticipated major surgical procedure during the course of the study

• Other medical conditions including but not limited to:

  • History of liver disease such as cirrhosis, chronic active hepatitis, chronic persistent hepatitis or hepatitis B or C
  • Active infection requiring parenteral antibiotics
  • Poorly controlled high blood pressure (>=150 mm Hg systolic and/or 100 mmHg diastolic) despite treatment
  • New York Heart Association class II-IV congestive heart failure
  • Serious cardiac arrhythmia requiring medication
  • Myocardial infarction or unstable angina =< 6 months prior to registration/randomization
  • Clinically significant peripheral vascular disease
  • Deep venous thrombosis or pulmonary embolus =< 1 year of registration/randomization and/or ongoing need for full-dose oral or parenteral anticoagulation
  • Ongoing anti-platelet treatment other than low-dose aspirin (i.e., aspirin 81 mg orally [p.o.] daily)
  • Active bleeding or pathological conditions that carry high risk of bleeding (e.g., known esophageal varices, etc.)
  • Serious, non-healing wound (including wounds healing by secondary intention), ulcer or bone fracture
  • History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess =< 6 months prior to registration/randomization
  • History of central nervous system (CNS) disease (e.g., primary brain tumor, vascular abnormalities, etc.), clinically significant stroke or transient ischemic attack (TIA) =< 6 months prior to registration/randomization, seizures not controlled with standard medical therapy
  • Radiographically documented tumor invading major blood vessels
  • History of hypertensive crisis or hypertensive encephalopathy
  • Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN
  • Severely impaired lung function as defined as spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
  • A known history of human immunodeficiency virus (HIV) seropositivity

• Any of the following as this regimen may be harmful to a developing fetus or nursing child:

  • Pregnant women
  • Nursing women
  • Men and women of reproductive potential who are not using effective birth control methods must use highly effective contraception throughout the trail and for 6 months after last study treatment
• Existence of peripheral sensory neuropathy >= grade 2
• History of other malignancy =< 5 years with the exception of basal cell or squamous cell carcinoma of the skin, treated with local resection only, or carcinoma in situ (e.g. of the cervix, breast, prostate, etc.)
• =< 4 weeks since last day of adjuvant radiation therapy prior to registration or =< 2 weeks since last day of palliative radiation therapy; NOTE: patients who have had > 25% of their functional bone marrow irradiated are not eligible for this trial
• Active or recent history of hemoptysis (>= 1/2 teaspoon of bright red blood per episode) =< 30 days prior to registration
• Known hypersensitivity to any of the components of the everolimus, bevacizumab, carboplatin, or paclitaxel
• Current use of drugs that are known to be strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); note: if these agents are discontinued, everolimus therapy can begin >= 7 days after discontinuation of such agent
• Positive hepatitis B antigen (HBsAg) or hepatitis C serology (HCV) tests
• Planned immunization with attenuated live vaccines =< 7 days prior to registration or during study period; note: close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus; examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guérin (BCG), yellow fever, varicella and TY21a typhoid vaccines

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (bevacizumab, paclitaxel, and carboplatin); Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, paclitaxel IV over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Biological: bevacizumab; Given IV; Drug: paclitaxel; Given IV; Drug: carboplatin; Given IV
Experimental: Arm II(bevacizumab, paclitaxel, carboplatin, and everolimus); Patients receive bevacizumab, paclitaxel, and carboplatin as in Arm I. Patients also receive everolimus PO QD on 3 days a week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Biological: bevacizumab; Given IV; Drug: paclitaxel; Given IV; Drug: carboplatin; Given IV; Drug: everolimus; Given orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	The primary endpoint is progression-free survival (PFS) defined as the time from randomization to documentation of disease progression or death without documentation of progression. The distribution of PFS times will be estimated using the Kaplan-Meier method. Progression is defined using the RECIST Criteria as at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum of diameters recorded on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm of target lesions, or the appearance of one or more new lesions, unequivocal progression of existing non-target lesions, although unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.	Time from randomization to documentation of disease progression or death without documentation of progression;Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity	For this secondary endpoint, toxicity is defined as a grade 3 or higher adverse events that is classified as either possibly, probably, or definitely related to study treatment. The assignment of attribution to study treatment and grade (or degree of severity) of the adverse event are classified using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The percentage of participants reporting a grade 3 or higher toxicity is reported. For a list of all reported adverse events, please refer to the Adverse Events Section below.	Up to 5 years
Confirmed Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria	Confirmed Tumor Response: A confirmed tumor response is defined to be a CR or PR (by the RECIST criteria) noted as the objective status on 2 consecutive evaluations at least 8 weeks apart. The proportion of tumor responses will be estimated by the number of confirmed tumor responses divided by the total number of evaluable patients. A ninety percent confidence interval for the true proportion of confirmed tumor responses will be calculated assuming that the number of confirmed tumor responses follows a binomial distribution.	Up to 5 years
Overall Survival Time	Overall survival time is defined as the time from registration to death due to any cause. The distribution of survival times will be estimated using the method of Kaplan-Meier.	up to 5 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Robert McWilliams, MD, Mayo Clinic

Publications and helpful links

General Publications

• Slostad JA, Liu MC, Allred JB, Erickson LA, Rumilla KM, Block MS, Keppen M, King D, Markovic SN, McWilliams RR. BRAF V600 Mutation Detection in Plasma Cell-Free DNA: NCCTG N0879 (Alliance). Mayo Clin Proc Innov Qual Outcomes. 2021 Oct 13;5(6):1012-1020. doi: 10.1016/j.mayocpiqo.2021.05.003. eCollection 2021 Dec.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: September 11, 2009
• First Submitted That Met QC Criteria: September 11, 2009
• First Posted (Estimate): September 14, 2009

Study Record Updates

• Last Update Posted (Actual): April 4, 2017
• Last Update Submitted That Met QC Criteria: March 7, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: recurrent melanoma; Stage IV Skin Melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Carboplatin; Paclitaxel; Bevacizumab; Everolimus
• Other Study ID Numbers: NCCTG-N0879; NCI-2011-01968 (Registry Identifier: CTRP (Clinical Trials Reporting System)); CDR0000654465 (Registry Identifier: PDQ (Physician Data Query))