Carboplatin and Paclitaxel With or Without Sorafenib Tosylate in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

A Double-Blind, Randomized, Placebo-Controlled Phase III Trial of Carboplatin, Paclitaxel and Sorafenib Versus Carboplatin, Paclitaxel and Placebo in Patients With Unresectable Locally Advanced or Stage IV Melanoma

This randomized phase III trial studies carboplatin, paclitaxel, and sorafenib tosylate to see how well they work compared to carboplatin and paclitaxel in treating patients with stage III or stage IV melanoma that cannot be removed by surgery. 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. Sorafenib tosylate 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 giving carboplatin and paclitaxel together with sorafenib tosylate is more effective than carboplatin and paclitaxel in treating melanoma.

Study Overview

• Status: Completed
• Conditions: Stage IV Skin Melanoma; Recurrent Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Mucosal Melanoma; Stage IIIA Skin Melanoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Carboplatin; Other: Placebo; Other: Pharmacological Study; Drug: Paclitaxel; Drug: Sorafenib Tosylate

Detailed Description

PRIMARY OBJECTIVES:

I. To compare the overall survival of patients with unresectable stage III or stage IV melanoma treated with carboplatin, paclitaxel and placebo versus carboplatin, paclitaxel and sorafenib (sorafenib tosylate).

II. To compare progression-free survival, response rate, and safety of patients with unresectable stage III or stage IV melanoma treated with carboplatin, paclitaxel and placebo versus carboplatin, paclitaxel and sorafenib.

III. To analyze the pharmacokinetic and pharmacogenetic properties of sorafenib including angiogenesis, monooxygenases polymorphisms and multidrug resistance (MDR).

IV. To assess the association of expression markers in the patient tumor with clinical outcome.

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

Arm I: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1. Patients also receive sorafenib tosylate orally (PO) twice daily (BID) (approximately every 12 hours) on days 2-19.

Arm II: Patients receive paclitaxel and carboplatin as in Arm I. Patients also receive placebo PO BID (approximately every 12 hours) on days 2-19.

In both arms, treatment repeats every 21 days for 10 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease or who achieve a partial response or complete response may continue to receive sorafenib tosylate or placebo alone BID (approximately every 12 hours) on days 1-21. Courses with sorafenib tosylate or placebo repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

• Study Type: Interventional
• Enrollment (Actual): 823
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Sydney West Area Health Service-Westmead Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
  • Arkansas
    • Ft. Smith, Arkansas, United States, 72903
      • Mercy Hospital Fort Smith
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Greenbrae, California, United States, 94904
      • Marin Cancer Care Inc
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Oakland, California, United States, 94609
      • Bay Area Tumor Institute
    • Orange, California, United States, 92868
      • Saint Joseph Hospital - Orange
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute
    • Redwood City, California, United States, 94063
      • Kaiser Permanente-Redwood City
    • Richmond, California, United States, 94801
      • Kaiser Permanente-Richmond
    • Roseville, California, United States, 95661
      • Kaiser Permanente-Roseville
    • Sacramento, California, United States, 95825
      • Kaiser Permanente - Sacramento
    • San Diego, California, United States, 92108
      • Kaiser Permanente-San Diego Mission
    • San Diego, California, United States, 92161
      • Veterans Administration-San Diego Medical Center
    • San Francisco, California, United States, 94115
      • Kaiser Permanente-San Francisco
    • San Francisco, California, United States, 94118
      • California Pacific Medical Center-Pacific Campus
    • San Jose, California, United States, 95119
      • Kaiser Permanente-Santa Teresa-San Jose
    • Sana Rosa, California, United States, 95405
      • Santa Rosa Memorial Hospital
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente Medical Center - Santa Clara
    • Santa Rosa, California, United States, 95403
      • Kaiser Permanente-Santa Rosa
    • Vallejo, California, United States, 94589
      • Kaiser Permanente-Vallejo
  • Colorado
    • Aurora, Colorado, United States, 80012
      • The Medical Center of Aurora
    • Boulder, Colorado, United States, 80301
      • Boulder Community Hospital
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Denver, Colorado, United States, 80210
      • Porter Adventist Hospital
    • Denver, Colorado, United States, 80218
      • Presbyterian - Saint Lukes Medical Center - Health One
    • Denver, Colorado, United States, 80218
      • Exempla Saint Joseph Hospital
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
    • Lone Tree, Colorado, United States, 80124
      • Sky Ridge Medical Center
    • Longmont, Colorado, United States, 80501
      • Longmont United Hospital
    • Thornton, Colorado, United States, 80229
      • North Suburban Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Broward Health Medical Center
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital
    • Fort Meyers, Florida, United States, 33901
      • Southwest Florida Regional Medical Center
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Hollywood, Florida, United States, 33021
      • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
    • Jacksonville, Florida, United States, 32207
      • Baptist Cancer Institute
    • Jupiter, Florida, United States, 33458
      • Jupiter Medical Center
    • Lakeland, Florida, United States, 33805
      • Lakeland Regional Cancer Center
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Cancer Center
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center
    • Orlando, Florida, United States, 32803
      • Florida Hospital Orlando
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Albany, Georgia, United States, 31701
      • Phoebe Putney Memorial Hospital
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital
    • Atlanta, Georgia, United States, 30342
      • Atlanta Regional CCOP
    • Decatur, Georgia, United States, 30033
      • Dekalb Medical Center
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center
    • Macon, Georgia, United States, 31208
      • Medical Center of Central Georgia
    • Riverdale, Georgia, United States, 30274
      • Southern Regional Medical Center
    • Valdosta, Georgia, United States, 31603
      • South Georgia Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60625
      • Swedish Covenant Hospital
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Elgin, Illinois, United States, 60123
      • Advocate Sherman Hospital
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
    • Hinsdale, Illinois, United States, 60521
      • Hinsdale Hematology Oncology Associates Incorporated
    • Moline, Illinois, United States, 61265
      • Trinity Medical Center
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
    • Urbana, Illinois, United States, 61801
      • Carle Clinic-Urbana Main
  • Indiana
    • Bloomington, Indiana, United States, 47403
      • IU Health Bloomington
    • Fort Wayne, Indiana, United States, 46845
      • Fort Wayne Medical Oncology and Hematology Inc-Parkview
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Michigan City, Indiana, United States, 46360
      • Franciscan Saint Anthony Health-Michigan City
    • Mishawaka, Indiana, United States, 46545
      • Saint Joseph Regional Medical Center-Mishawaka
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
  • Iowa
    • Cedar Rapids, Iowa, United States, 52403
      • Cedar Rapids Oncology Association
    • Cedar Rapids, Iowa, United States, 52402
      • Physicians' Clinic of Iowa PC
    • Council Bluffs, Iowa, United States, 51503
      • Heartland Oncology and Hematology LLP
    • Davenport, Iowa, United States, 52803
      • Genesis Medical Center - East Campus
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates-Des Moines
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates-Laurel
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
    • Waterloo, Iowa, United States, 50701
      • Cedar Valley Medical Specialists
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas - Chanute
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Prairie Village, Kansas, United States, 66208
      • Kansas City CCOP
    • Salina, Kansas, United States, 67401
      • Salina Regional Health Center
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas - Wellington
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Main Office
  • Maine
    • Lewiston, Maine, United States, 04240
      • Central Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • MedStar Franklin Square Medical Center/Weinberg Cancer Institute
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
    • Frederick, Maryland, United States, 21701
      • Frederick Memorial Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Worcester, Massachusetts, United States, 01605
      • Commonwealth Hematology Oncology PC-Worcester
  • Michigan
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Hospital
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
    • Dearborn, Michigan, United States, 48124
      • Oakwood Hospital and Medical Center
    • Detroit, Michigan, United States, 48236
      • Saint John Hospital and Medical Center
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Flint, Michigan, United States, 48502
      • Hurley Medical Center
    • Grand Rapids, Michigan, United States, 49503
      • Grand Rapids Clinical Oncology Program
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital-Royal Oak
    • Saint Joseph, Michigan, United States, 49085
      • Oncology Care Associates PLLC
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
  • Minnesota
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology and Hematology PA-Woodbury
  • Mississippi
    • Pascagoula, Mississippi, United States, 39581
      • Singing River Hospital
  • Missouri
    • Joplin, Missouri, United States, 64804
      • Freeman Health System
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • Saint Louis, Missouri, United States, 63141
      • Saint Louis-Cape Girardeau CCOP
    • Saint Louis, Missouri, United States, 63141
      • Center for Cancer Care and Research
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
  • Montana
    • Billings, Montana, United States, 59102
      • Frontier Cancer Center and Blood Institute-Billings
    • Billings, Montana, United States, 59101
      • Montana Cancer Consortium NCORP
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Nevada Cancer Research Foundation CCOP
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • East Orange, New Jersey, United States, 07018-1095
      • Veterans Adminstration New Jersey Health Care System
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical CCOP
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
  • New York
    • Bronx, New York, United States, 10466
      • Montefiore Medical Center-Wakefield Campus
    • East Syracuse, New York, United States, 13057
      • Hematology Oncology Associates of Central New York-East Syracuse
    • Glens Falls, New York, United States, 12801
      • Glens Falls Hospital
    • New York, New York, United States, 10016
      • Laura and Issac Perlmutter Cancer Center at NYU Langone
    • Poughkeepsie, New York, United States, 12601
      • MidHudson Regional Hospital of Westchester Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Rochester, New York, United States, 14623
      • Interlakes Foundation Inc-Rochester
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center/Levine Cancer Institute
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
    • Greenville, North Carolina, United States, 27858
      • East Carolina University
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic
    • Fargo, North Dakota, United States, 58122
      • Sanford Medical Center-Fargo
    • Grand Forks, North Dakota, United States, 58201
      • Altru Cancer Center
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Akron City Hospital/Cooper Cancer Center
    • Canton, Ohio, United States, 44710
      • Aultman Health Foundation
    • Canton, Ohio, United States, 44708
      • Mercy Medical Center
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health Center West
    • Columbus, Ohio, United States, 43215
      • Columbus CCOP
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Independence, Ohio, United States, 44131
      • Cleveland Clinic Cancer Center Independence
    • Lima, Ohio, United States, 45801
      • Saint Rita's Medical Center
    • Newark, Ohio, United States, 43055
      • Licking Memorial Hospital
    • Springfield, Ohio, United States, 45505
      • Springfield Regional Medical Center
    • Wooster, Ohio, United States, 44691
      • Cleveland Clinic Wooster Specialty Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Oklahoma City, Oklahoma, United States, 73120
      • Cancer Care Associates
  • Oregon
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente
    • Portland, Oregon, United States, 97213
      • Western Oncology Research Consortium
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Drexel Hill, Pennsylvania, United States, 19026
      • Delaware County Memorial Hospital
    • Dubois, Pennsylvania, United States, 15801
      • Oncology Hematology Associates of Northern Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17109
      • PinnacleHealth Cancer Center-Community Campus
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Milton S Hershey Medical Center
    • Langhorne, Pennsylvania, United States, 19047
      • Saint Mary Medical and Regional Cancer Center
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania/Abramson Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Pennsylvania Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute (UPCI)
    • Pottstown, Pennsylvania, United States, 19464
      • Pottstown Memorial Medical Center
    • Scranton, Pennsylvania, United States, 18510
      • Scranton Hematology Oncology
    • Scranton, Pennsylvania, United States, 18508
      • Hematology and Oncology Associates of North East Pennsylvania
    • State College, Pennsylvania, United States, 16801
      • Geisinger Medical Group
    • West Chester, Pennsylvania, United States, 19380
      • Chester County Hospital
    • West Grove, Pennsylvania, United States, 19390
      • Jennersville Regional Hospital
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
    • York, Pennsylvania, United States, 17405
      • WellSpan Health-York Hospital
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Kent County Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Florence, South Carolina, United States, 29506
      • McLeod Regional Medical Center
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Center-Oncology Clinic
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Erlanger Medical Center
    • Knoxville, Tennessee, United States, 37920
      • East Tennessee Baptist Hospital-Mercy Health Partners
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University/Ingram Cancer Center
  • Vermont
    • Burlington, Vermont, United States, 05405
      • University of Vermont College of Medicine
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center
    • Charlottesville, Virginia, United States, 22901
      • Martha Jefferson Hospital
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center
    • Hampton, Virginia, United States, 23666
      • Virginia Oncology Associates-Hampton
  • Washington
    • Seattle, Washington, United States, 98112
      • Group Health Cooperative-Seattle
    • Seattle, Washington, United States, 98122-4307
      • Swedish Medical Center-First Hill
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • West Virginia University Charleston
    • Huntington, West Virginia, United States, 25701
      • Edwards Comprehensive Cancer Center
    • Huntington, West Virginia, United States, 25702
      • Saint Mary's Medical Center
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Healthcare
  • Wisconsin
    • Appleton, Wisconsin, United States, 54911
      • Fox Valley Hematology and Oncology
    • Elkhorn, Wisconsin, United States, 53121
      • Aurora Cancer Care-Southern Lakes
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Madison, Wisconsin, United States, 53717
      • Dean Hematology and Oncology Clinic
    • Manitowoc, Wisconsin, United States, 54221
      • Holy Family Memorial Hospital
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and The Medical College of Wisconsin

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:

• Histological or cytological confirmed melanoma that is metastatic or unresectable; patients must have a history of cutaneous, mucosal or unknown primary site

• Patients who have received prior systemic cytotoxic chemotherapy for treatment of melanoma are ineligible; the following groups are eligible with regard to prior systemic therapy either in the adjuvant or metastatic disease setting:

  • No prior therapy
  • Immunotherapy consisting of interferon, interleukin-2, granulocyte macrophage colony-stimulating factor (GM-CSF) or vaccine

  • One prior investigational therapy (cannot be chemotherapy or an inhibitor of rat sarcoma [Ras], serine/threonine kinase [Raf], or mitogen-activated protein kinase kinase [MEK])

    • NOTE: Chemotherapy given via isolated limb perfusion is allowed
• Prior radiation therapy is allowed; however, if radiation has been administered to a lesion, there must be radiographic evidence of progression of that lesion in order for that lesion to constitute measurable disease or to be included in the measured target lesions
• All sites of disease must be evaluated within 4 weeks of registration; patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• White blood count >= 3,000/mm^3
• Absolute granulocyte count >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Serum creatinine =< 2.0 x upper limit of normal (ULN) or serum creatinine clearance (CrCl) >= 40 ml/min (neither drug is cleared by the kidney)
• Total bilirubin =< 1.5 x ULN (< 3.0 x ULN in the presence of Gilbert's disease)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN (=< 5.0 ULN in the presence of liver metastases)
• International normalized ratio (INR) =< 1.5 and a partial thromboplastin time (PTT) within normal limits (patients who are on therapeutic anticoagulation with warfarin should have documentation of a normal prothrombin time [PT]/PTT prior to initiating that therapy)
• Patients must not have ocular melanoma
• Patients must have discontinued immunotherapy or radiation therapy at least 4 weeks prior to initiation of treatment and recovered from adverse events due to those agents
• Patients must not receive any other investigational agents during the period on study or the four weeks prior to initiation of treatment
• Patients must not have a history or clinical evidence of brain metastasis; patients must be evaluated with a head magnetic resonance imaging (MRI) within 4 weeks prior to enrollment
• Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast; patients with other malignancies are eligible if they have been continuously disease-free for >= 5 years prior to the time of randomization
• Patients must not have any evidence of bleeding diathesis
• Patients must not have a serious intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, clinically significant cardiovascular disease (e.g. uncontrolled hypertension, myocardial infarction, unstable angina), New York Heart Association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or grade II or greater peripheral vascular disease within 1 year prior to study entry, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients must not be taking cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or phenobarbital), rifampin or St. John's Wort
• Women must not be pregnant or breast-feeding
• All females of childbearing potential must have a blood test or urine study within 4 weeks prior to registration to rule out pregnancy
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately as well
• Human immunodeficiency virus (HIV)-positive patients are excluded from the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (paclitaxel, carboplatin, sorafenib tosylate); Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Patients also receive sorafenib tosylate PO BID (approximately every 12 hours) on days 2-19.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Carboplatin; Given IV; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; Paraplat; Other: Pharmacological Study; Correlative studies; Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Drug: Sorafenib Tosylate; Given PO; Other Names: BAY 54-9085; Nexavar; BAY 43-9006 Tosylate; sorafenib
Active Comparator: Arm II (carboplatin, paclitaxel, placebo); Patients receive paclitaxel and carboplatin as in Arm I. Patients also receive placebo PO BID (approximately every 12 hours) on days 2-19.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Carboplatin; Given IV; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; Paraplat; Other: Placebo; Given PO; Other Names: placebo therapy; PLCB; sham therapy; Other: Pharmacological Study; Correlative studies; Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival is defined as time from study entry to death from any cause. The comparison of overall survival was conducted in intention-to-treat population.	Survival was assessed every 3 months if patient is < 2 years from study entry. Every 6 months is patient is 2-5 years from study entry.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Progression-free survival was defined as time from study entry to disease progression or death from any cause, whichever occurred first. Patients without disease progression were censored at last date of assessment. Disease progression was assessed by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0.	Tumor response was assessed after every 2 cycles during cycle 1 through 10, and every 3 cycles after cycle 10. Survival was assessed every 3 months if patient is < 2 years from study entry, and every 6 months if 2-5 years from study entry.
Objective Response (Complete and Partial Response) Rate	Tumor response was assessed by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0. Objective response =complete response (CR) + partial response (PR). Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum of longest diameters.	Tumor response was assessed after every 2 cycles during cycle 1 through 10. After cycle 10, tumor response was assessed after every 3 cycles.

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Keith Flaherty, ECOG-ACRIN Cancer Research Group

Publications and helpful links

General Publications

• Flaherty KT, Lee SJ, Zhao F, Schuchter LM, Flaherty L, Kefford R, Atkins MB, Leming P, Kirkwood JM. Phase III trial of carboplatin and paclitaxel with or without sorafenib in metastatic melanoma. J Clin Oncol. 2013 Jan 20;31(3):373-9. doi: 10.1200/JCO.2012.42.1529. Epub 2012 Dec 17.

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: May 3, 2005
• First Submitted That Met QC Criteria: May 3, 2005
• First Posted (Estimate): May 4, 2005

Study Record Updates

• Last Update Posted (Estimate): October 19, 2015
• Last Update Submitted That Met QC Criteria: September 28, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Skin Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Carboplatin; Paclitaxel; Sorafenib; Albumin-Bound Paclitaxel
• Other Study ID Numbers: NCI-2012-02978 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180820 (U.S. NIH Grant/Contract); U10CA021115 (U.S. NIH Grant/Contract); E2603 (Other Identifier: CTEP)