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

About this trial
This is an interventional treatment trial for Melanoma (Skin) focused on measuring Stage IV Skin Melanoma, recurrent melanoma
Eligibility Criteria
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
Sites / Locations
- Mayo Clinic Scottsdale
- Contra Costa Regional Medical Center
- El Camino Hospital Cancer Center
- Bay Area Breast Surgeons, Incorporated
- CCOP - Bay Area Tumor Institute
- Larry G Strieff MD Medical Corporation
- Tom K Lee, Incorporated
- Doctors Medical Center - San Pablo Campus
- Aurora Presbyterian Hospital
- Boulder Community Hospital
- Penrose Cancer Center at Penrose Hospital
- St. Anthony Central Hospital
- Porter Adventist Hospital
- Presbyterian - St. Luke's Medical Center
- St. Joseph Hospital
- Rose Medical Center
- Swedish Medical Center
- Poudre Valley Hospital
- Front Range Cancer Specialists
- North Colorado Medical Center
- Sky Ridge Medical Center
- Hope Cancer Care Center at Longmont United Hospital
- McKee Medical Center
- St. Mary - Corwin Regional Medical Center
- North Suburban Medical Center
- Exempla Lutheran Medical Center
- Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
- Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
- Baptist Cancer Institute - Jacksonville
- Mayo Clinic - Jacksonville
- Ella Milbank Foshay Cancer Center at Jupiter Medical Center
- Lakeland Regional Cancer Center at Lakeland Regional Medical Center
- CCOP - Mount Sinai Medical Center
- John B. Amos Cancer Center
- Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
- Rush-Copley Cancer Care Center
- Illinois CancerCare - Bloomington
- St. Joseph Medical Center
- Illinois CancerCare - Canton
- Illinois CancerCare - Carthage
- Eureka Community Hospital
- Illinois CancerCare - Eureka
- Galesburg Clinic, PC
- Illinois CancerCare - Havana
- Illinois CancerCare - Kewanee Clinic
- La Grange Memorial Hospital
- Illinois CancerCare - Macomb
- Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
- Illinois CancerCare - Monmouth
- OSF Holy Family Medical Center
- BroMenn Regional Medical Center
- Community Cancer Center
- Illinois CancerCare - Community Cancer Center
- Community Hospital of Ottawa
- Oncology Hematology Associates of Central Illinois, PC - Ottawa
- Cancer Treatment Center at Pekin Hospital
- Illinois CancerCare - Pekin
- Proctor Hospital
- CCOP - Illinois Oncology Research Association
- Oncology Hematology Associates of Central Illinois, PC - Peoria
- Methodist Medical Center of Illinois
- OSF St. Francis Medical Center
- Illinois CancerCare - Peru
- Illinois Valley Community Hospital
- Illinois CancerCare - Princeton
- Illinois CancerCare - Spring Valley
- CCOP - Carle Cancer Center
- Elkhart Clinic, LLC
- Michiana Hematology-Oncology, PC - Elkhart
- Elkhart General Hospital
- St. Francis Hospital Cancer Care Services
- Howard Community Hospital
- Center for Cancer Therapy at LaPorte Hospital and Health Services
- Saint Anthony Memorial Health Centers
- Michiana Hematology-Oncology, PC - South Bend
- Saint Joseph Regional Medical Center
- Michiana Hematology Oncology PC - Plymouth
- Reid Hospital & Health Care Services
- CCOP - Northern Indiana CR Consortium
- Memorial Hospital of South Bend
- Michiana Hematology Oncology PC - La Porte
- McFarland Clinic, PC
- Cedar Rapids Oncology Associates
- Mercy Regional Cancer Center at Mercy Medical Center
- Medical Oncology and Hematology Associates - West Des Moines
- Mercy Cancer Center - West Lakes
- CCOP - Iowa Oncology Research Association
- John Stoddard Cancer Center at Iowa Methodist Medical Center
- Medical Oncology and Hematology Associates at John Stoddard Cancer Center
- Medical Oncology and Hematology Associates at Mercy Cancer Center
- Mercy Cancer Center at Mercy Medical Center - Des Moines
- John Stoddard Cancer Center at Iowa Lutheran Hospital
- Holden Comprehensive Cancer Center at University of Iowa
- Mercy Cancer Center at Mercy Medical Center - North Iowa
- McCreery Cancer Center at Ottumwa Regional
- Siouxland Hematology-Oncology Associates, LLP
- Mercy Medical Center - Sioux City
- St. Luke's Regional Medical Center
- Methodist West Hospital
- Cancer Center of Kansas, PA - Chanute
- Cancer Center of Kansas, PA - Dodge City
- Cancer Center of Kansas, PA - El Dorado
- Cancer Center of Kansas - Fort Scott
- Cancer Center of Kansas-Independence
- Cancer Center of Kansas, PA - Kingman
- Lawrence Memorial Hospital
- Cancer Center of Kansas, PA - Liberal
- Cancer Center of Kansas, PA - Newton
- Menorah Medical Center
- Saint Luke's Hospital - South
- Cancer Center of Kansas, PA - Parsons
- CCOP - Kansas City
- Cancer Center of Kansas, PA - Pratt
- Cancer Center of Kansas, PA - Salina
- Cancer Center of Kansas, PA - Wellington
- Associates in Womens Health, PA - North Review
- Cancer Center of Kansas, PA - Medical Arts Tower
- Cancer Center of Kansas, PA - Wichita
- CCOP - Wichita
- Via Christi Cancer Center at Via Christi Regional Medical Center
- Cancer Center of Kansas, PA - Winfield
- Boston University Cancer Research Center
- Hickman Cancer Center at Bixby Medical Center
- Saint Joseph Mercy Cancer Center
- CCOP - Michigan Cancer Research Consortium
- Battle Creek Health System Cancer Care Center
- Mecosta County Medical Center
- Oakwood Cancer Center at Oakwood Hospital and Medical Center
- Green Bay Oncology, Limited - Escanaba
- Genesys Hurley Cancer Institute
- Hurley Medical Center
- Butterworth Hospital at Spectrum Health
- CCOP - Grand Rapids
- Lacks Cancer Center at Saint Mary's Health Care
- Van Elslander Cancer Center at St. John Hospital and Medical Center
- Dickinson County Healthcare System
- Foote Memorial Hospital
- Sparrow Regional Cancer Center
- St. Mary Mercy Hospital
- Community Cancer Center of Monroe
- Mercy Memorial Hospital - Monroe
- Mercy General Health Partners
- St. Joseph Mercy Oakland
- Mercy Regional Cancer Center at Mercy Hospital
- Spectrum Health Reed City Hospital
- Seton Cancer Institute at Saint Mary's - Saginaw
- Lakeland Regional Cancer Care Center - St. Joseph
- Lakeside Cancer Specialists, PLLC
- Munson Medical Center
- St. John Macomb Hospital
- MeritCare Bemidji
- St. Joseph's Medical Center
- Fairview Ridges Hospital
- Mercy and Unity Cancer Center at Mercy Hospital
- Essentia Health - Duluth Clinic
- CCOP - Duluth
- Miller - Dwan Medical Center
- Fairview Southdale Hospital
- Mercy and Unity Cancer Center at Unity Hospital
- Hutchinson Area Health Care
- HealthEast Cancer Care at St. John's Hospital
- Minnesota Oncology - Maplewood
- Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
- Hennepin County Medical Center - Minneapolis
- Humphrey Cancer Center at North Memorial Outpatient Center
- Mayo Clinic Cancer Center
- CentraCare Clinic - River Campus
- Coborn Cancer Center
- CCOP - Metro-Minnesota
- Park Nicollet Cancer Center
- United Hospital
- St. Francis Cancer Center at St. Francis Medical Center
- Regions Hospital Cancer Care Center
- Lakeview Hospital
- Ridgeview Medical Center
- Willmar Cancer Center at Rice Memorial Hospital
- Minnesota Oncology - Woodbury
- Southeast Cancer Center
- Ellis Fischel Cancer Center at University of Missouri - Columbia
- Goldschmidt Cancer Center
- Saint Luke's Cancer Institute at Saint Luke's Hospital
- North Kansas City Hospital
- Heartland Hematology Oncology Associates, Incorporated
- Research Medical Center
- Saint Luke's East - Lee's Summit
- Mercy Clinic Cancer and Hematology - Rolla
- Saint Joseph Oncology, Incorporated
- Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
- Missouri Baptist Cancer Center
- CCOP - Cancer Research for the Ozarks
- St. John's Regional Health Center
- Hulston Cancer Center at Cox Medical Center South
- CCOP - Montana Cancer Consortium
- St. Vincent Healthcare Cancer Care Services
- Hematology-Oncology Centers of the Northern Rockies - Billings
- Billings Clinic - Downtown
- Bozeman Deaconess Cancer Center
- St. James Healthcare Cancer Care
- Benefis Sletten Cancer Institute
- St. Peter's Hospital
- Kalispell Regional Medical Center
- Montana Cancer Specialists at Montana Cancer Center
- Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
- Cancer Resource Center - Lincoln
- CCOP - Missouri Valley Cancer Consortium
- Immanuel Medical Center
- Alegant Health Cancer Center at Bergan Mercy Medical Center
- Lakeside Hospital
- Creighton University Medical Center
- University Medical Center of Southern Nevada
- CCOP - Nevada Cancer Research Foundation
- Charles R. Wood Cancer Center at Glens Falls Hospital
- Randolph Hospital
- Wayne Memorial Hospital, Incorporated
- Moses Cone Regional Cancer Center at Wesley Long Community Hospital
- Pardee Memorial Hospital
- Kinston Medical Specialists
- FirstHealth Moore Regional Community Hospital Comprehensive Cancer Center
- Annie Penn Cancer Center
- Iredell Memorial Hospital
- Medcenter One Hospital Cancer Care Center
- Mid Dakota Clinic, PC
- St. Alexius Medical Center Cancer Center
- MeritCare Broadway
- Altru Cancer Center at Altru Hospital
- Wood County Oncology Center
- Adena Regional Medical Center
- Riverside Methodist Hospital Cancer Care
- CCOP - Columbus
- Grant Medical Center Cancer Care
- Mount Carmel Health - West Hospital
- Doctors Hospital at Ohio Health
- Grandview Hospital
- Good Samaritan Hospital
- David L. Rike Cancer Center at Miami Valley Hospital
- Samaritan North Cancer Care Center
- CCOP - Dayton
- Grady Memorial Hospital
- Community Cancer Center
- Hematology Oncology Center
- Blanchard Valley Medical Associates
- Middletown Regional Hospital
- Wayne Hospital
- Charles F. Kettering Memorial Hospital
- Fairfield Medical Center
- Lima Memorial Hospital
- Strecker Cancer Center at Marietta Memorial Hospital
- Northwest Ohio Oncology Center
- Knox Community Hospital
- Licking Memorial Cancer Care Program at Licking Memorial Hospital
- St. Charles Mercy Hospital
- Toledo Clinic - Oregon
- Southern Ohio Medical Center Cancer Center
- Community Hospital of Springfield and Clark County
- Flower Hospital Cancer Center
- Mercy Hospital of Tiffin
- Toledo Hospital
- St. Vincent Mercy Medical Center
- Medical University of Ohio Cancer Center
- St. Anne Mercy Hospital
- Toledo Clinic, Incorporated - Main Clinic
- UVMC Cancer Care Center at Upper Valley Medical Center
- Fulton County Health Center
- Mount Carmel St. Ann's Cancer Center
- Ruth G. McMillan Cancer Center at Greene Memorial Hospital
- Genesis - Good Samaritan Hospital
- Cancer Care Associates - Norman
- Cancer Care Associates - Mercy Campus
- Natalie Warren Bryant Cancer Center at St. Francis Hospital
- Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
- Geisinger Cancer Institute at Geisinger Health
- Geisinger Hazleton Cancer Center
- Guthrie Cancer Center at Guthrie Clinic Sayre
- Geisinger Medical Group - Scenery Park
- Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
- Cancer Centers of the Carolinas - Faris Road
- Cancer Centers of the Carolinas - Grove Commons
- Greenville Hospital Cancer Center
- CCOP - Greenville
- Cancer Centers of the Carolinas - Greer Medical Oncology
- Cancer Centers of the Carolinas - Seneca
- Cancer Centers of the Carolinas - Spartanburg
- Rapid City Regional Hospital
- Sanford Cancer Center at Sanford USD Medical Center
- Danville Regional Medical Center
- Fredericksburg Oncology, Incorporated
- Mary Babb Randolph Cancer Center at West Virginia University Hospitals
- Center for Cancer Treatment & Prevention at Sacred Heart Hospital
- Marshfield Clinic Cancer Care at Regional Cancer Center
- Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
- Green Bay Oncology, Limited at St. Mary's Hospital
- St. Mary's Hospital Medical Center - Green Bay
- St. Vincent Hospital Regional Cancer Center
- Gundersen Lutheran Center for Cancer and Blood
- Holy Family Memorial Medical Center Cancer Care Center
- Bay Area Cancer Care Center at Bay Area Medical Center
- Marshfield Clinic - Marshfield Center
- Saint Joseph's Hospital
- Marshfield Clinic - Lakeland Center
- Green Bay Oncology, Limited - Oconto Falls
- Ministry Medical Group at Saint Mary's Hospital
- Marshfield Clinic - Indianhead Center
- St. Nicholas Hospital
- Marshfield Clinic at Saint Michael's Hospital
- Saint Michael's Hospital Cancer Center
- Green Bay Oncology, Limited - Sturgeon Bay
- Marshfield Clinic - Weston Center
- Marshfield Clinic - Wisconsin Rapids Center
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm I (bevacizumab, paclitaxel, and carboplatin)
Arm II(bevacizumab, paclitaxel, carboplatin, and everolimus)
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.
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.