Melanoma Clinical Trial
Carboplatin and Paclitaxel With or Without Sorafenib Tosylate in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery
Summary
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.
Full 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.
Eligibility Criteria
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
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There are 213 Locations for this study
Birmingham Alabama, 35233, United States
Ft. Smith Arkansas, 72903, United States
Little Rock Arkansas, 72205, United States
Burbank California, 91505, United States
Duarte California, 91010, United States
Greenbrae California, 94904, United States
La Jolla California, 92093, United States
Los Angeles California, 90033, United States
Oakland California, 94609, United States
Orange California, 92868, United States
Palo Alto California, 94304, United States
Redwood City California, 94063, United States
Richmond California, 94801, United States
Roseville California, 95661, United States
Sacramento California, 95825, United States
San Diego California, 92108, United States
San Diego California, 92161, United States
San Francisco California, 94115, United States
San Francisco California, 94118, United States
San Jose California, 95119, United States
Sana Rosa California, 95405, United States
Santa Clara California, 95051, United States
Santa Rosa California, 95403, United States
Vallejo California, 94589, United States
Aurora Colorado, 80012, United States
Boulder Colorado, 80301, United States
Colorado Springs Colorado, 80907, United States
Denver Colorado, 80210, United States
Denver Colorado, 80218, United States
Denver Colorado, 80218, United States
Englewood Colorado, 80113, United States
Lone Tree Colorado, 80124, United States
Longmont Colorado, 80501, United States
Thornton Colorado, 80229, United States
Hartford Connecticut, 06102, United States
New Haven Connecticut, 06520, United States
Lewes Delaware, 19958, United States
Newark Delaware, 19718, United States
Fort Lauderdale Florida, 33308, United States
Fort Lauderdale Florida, 33316, United States
Fort Meyers Florida, 33901, United States
Gainesville Florida, 32610, United States
Hollywood Florida, 33021, United States
Jacksonville Florida, 32207, United States
Jupiter Florida, 33458, United States
Lakeland Florida, 33805, United States
Miami Beach Florida, 33140, United States
Miami Florida, 33136, United States
Orlando Florida, 32803, United States
Tampa Florida, 33612, United States
Albany Georgia, 31701, United States
Atlanta Georgia, 30309, United States
Atlanta Georgia, 30342, United States
Decatur Georgia, 30033, United States
Gainesville Georgia, 30501, United States
Macon Georgia, 31208, United States
Riverdale Georgia, 30274, United States
Valdosta Georgia, 31603, United States
Honolulu Hawaii, 96813, United States
Chicago Illinois, 60625, United States
Chicago Illinois, 60637, United States
Decatur Illinois, 62526, United States
Elgin Illinois, 60123, United States
Evanston Illinois, 60201, United States
Hinsdale Illinois, 60521, United States
Moline Illinois, 61265, United States
Springfield Illinois, 62781, United States
Urbana Illinois, 61801, United States
Urbana Illinois, 61801, United States
Bloomington Indiana, 47403, United States
Fort Wayne Indiana, 46845, United States
Indianapolis Indiana, 46202, United States
Michigan City Indiana, 46360, United States
Mishawaka Indiana, 46545, United States
South Bend Indiana, 46601, United States
Cedar Rapids Iowa, 52402, United States
Cedar Rapids Iowa, 52403, United States
Council Bluffs Iowa, 51503, United States
Davenport Iowa, 52803, United States
Des Moines Iowa, 50309, United States
Des Moines Iowa, 50314, United States
Iowa City Iowa, 52242, United States
Waterloo Iowa, 50701, United States
Chanute Kansas, 66720, United States
Kansas City Kansas, 66160, United States
Prairie Village Kansas, 66208, United States
Salina Kansas, 67401, United States
Wellington Kansas, 67152, United States
Wichita Kansas, 67208, United States
Wichita Kansas, 67214, United States
Lewiston Maine, 04240, United States
Baltimore Maryland, 21204, United States
Baltimore Maryland, 21215, United States
Baltimore Maryland, 21237, United States
Baltimore Maryland, 21287, United States
Frederick Maryland, 21701, United States
Boston Massachusetts, 02114, United States
Boston Massachusetts, 02115, United States
Boston Massachusetts, 02215, United States
Worcester Massachusetts, 01605, United States
Ann Arbor Michigan, 48106, United States
Ann Arbor Michigan, 48109, United States
Dearborn Michigan, 48124, United States
Detroit Michigan, 48201, United States
Detroit Michigan, 48236, United States
Flint Michigan, 48502, United States
Grand Rapids Michigan, 49503, United States
Kalamazoo Michigan, 49007, United States
Royal Oak Michigan, 48073, United States
Saint Joseph Michigan, 49085, United States
Traverse City Michigan, 49684, United States
Warren Michigan, 48093, United States
Fridley Minnesota, 55432, United States
Minneapolis Minnesota, 55407, United States
Robbinsdale Minnesota, 55422, United States
Saint Louis Park Minnesota, 55416, United States
Saint Paul Minnesota, 55101, United States
Saint Paul Minnesota, 55102, United States
Shakopee Minnesota, 55379, United States
Woodbury Minnesota, 55125, United States
Pascagoula Mississippi, 39581, United States
Joplin Missouri, 64804, United States
Saint Louis Missouri, 63141, United States
Saint Louis Missouri, 63141, United States
Saint Louis Missouri, 63141, United States
Springfield Missouri, 65804, United States
Springfield Missouri, 65807, United States
Billings Montana, 59101, United States
Billings Montana, 59102, United States
Las Vegas Nevada, 89106, United States
Lebanon New Hampshire, 03756, United States
East Orange New Jersey, 07018, United States
Hackensack New Jersey, 07601, United States
New Brunswick New Jersey, 08903, United States
Bronx New York, 10466, United States
East Syracuse New York, 13057, United States
Glens Falls New York, 12801, United States
New York New York, 10016, United States
Poughkeepsie New York, 12601, United States
Rochester New York, 14623, United States
Rochester New York, 14642, United States
Stony Brook New York, 11794, United States
Syracuse New York, 13210, United States
Charlotte North Carolina, 28203, United States
Durham North Carolina, 27710, United States
Goldsboro North Carolina, 27534, United States
Greenville North Carolina, 27858, United States
Bismarck North Dakota, 58501, United States
Fargo North Dakota, 58122, United States
Grand Forks North Dakota, 58201, United States
Akron Ohio, 44304, United States
Canton Ohio, 44708, United States
Canton Ohio, 44710, United States
Chillicothe Ohio, 45601, United States
Cincinnati Ohio, 45219, United States
Cleveland Ohio, 44106, United States
Cleveland Ohio, 44195, United States
Columbus Ohio, 43210, United States
Columbus Ohio, 43215, United States
Columbus Ohio, 43215, United States
Columbus Ohio, 43222, United States
Columbus Ohio, 43228, United States
Delaware Ohio, 43015, United States
Independence Ohio, 44131, United States
Lima Ohio, 45801, United States
Newark Ohio, 43055, United States
Springfield Ohio, 45505, United States
Wooster Ohio, 44691, United States
Oklahoma City Oklahoma, 73104, United States
Oklahoma City Oklahoma, 73120, United States
Portland Oregon, 97213, United States
Portland Oregon, 97227, United States
Danville Pennsylvania, 17822, United States
Drexel Hill Pennsylvania, 19026, United States
Dubois Pennsylvania, 15801, United States
Harrisburg Pennsylvania, 17109, United States
Hershey Pennsylvania, 17033, United States
Langhorne Pennsylvania, 19047, United States
Philadelphia Pennsylvania, 19104, United States
Philadelphia Pennsylvania, 19107, United States
Philadelphia Pennsylvania, 19107, United States
Philadelphia Pennsylvania, 19111, United States
Pittsburgh Pennsylvania, 15232, United States
Pottstown Pennsylvania, 19464, United States
Scranton Pennsylvania, 18508, United States
Scranton Pennsylvania, 18510, United States
State College Pennsylvania, 16801, United States
West Chester Pennsylvania, 19380, United States
West Grove Pennsylvania, 19390, United States
Wynnewood Pennsylvania, 19096, United States
York Pennsylvania, 17405, United States
Warwick Rhode Island, 02886, United States
Charleston South Carolina, 29425, United States
Florence South Carolina, 29506, United States
Rapid City South Dakota, 57701, United States
Sioux Falls South Dakota, 57104, United States
Chattanooga Tennessee, 37403, United States
Knoxville Tennessee, 37920, United States
Nashville Tennessee, 37232, United States
Burlington Vermont, 05405, United States
Charlottesville Virginia, 22901, United States
Charlottesville Virginia, 22908, United States
Danville Virginia, 24541, United States
Hampton Virginia, 23666, United States
Seattle Washington, 98112, United States
Seattle Washington, 98122, United States
Charleston West Virginia, 25304, United States
Huntington West Virginia, 25701, United States
Huntington West Virginia, 25702, United States
Morgantown West Virginia, 26506, United States
Appleton Wisconsin, 54911, United States
Elkhorn Wisconsin, 53121, United States
La Crosse Wisconsin, 54601, United States
Madison Wisconsin, 53717, United States
Madison Wisconsin, 53792, United States
Manitowoc Wisconsin, 54221, United States
Marshfield Wisconsin, 54449, United States
Milwaukee Wisconsin, 53226, United States
Westmead New South Wales, 2145, Australia
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