The primary objectives of this study are:

• To explore the antitumor activity of MEDI-522 ± DTIC in patients with metastatic melanoma.
• To determine the safety of MEDI-522 ± DTIC in this patient population.

Condition	Treatment or Intervention	Phase
Melanoma Malignant Metastatic Melanoma	Drug: MEDI-522	Phase II

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion

Patients must meet all of the following criteria at the time of randomization:

• Histologically confirmed, unresectable, Stage IV metastatic melanoma (AJCC staging), with at least one measurable lesion defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ³ 20 mm with conventional techniques or as ³ 10 mm with spiral computed tomography (CT) scan;
• Adult men and women of at least 18 years of age at the time of randomization;
• Women of reproductive potential (defined as being <1 year post-menopausal) must have a negative serum β human chorionic gonadotropin (βhCG) pregnancy test within 3 days prior to randomization; and men and women of reproductive potential must agree to practice an effective method of avoiding pregnancy (including oral or implanted contraceptives, intrauterine device (IUD), condom, diaphragm with spermicide, cervical cap, abstinence, or sterile sexual partner) at the time the informed consent is signed, and must agree to continue using such precautions while receiving MEDI-522 and for 30 days after the final dose of MEDI-522;
• Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1;
• Life expectancy of at least 16 weeks;
• WBC ≥ 3,000/mm3, absolute neutrophil count (ANC) ≥ 1,500/mm3, platelet count ≥ 100,000/mm3;
• Bilirubin ≤ 1.5 mg/dL, aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 3 times upper limit of normal (ULN), serum creatinine ≤ 1.5 mg/dL, alkaline phosphatase ≤ 3.0 times ULN and prothrombin time (PT)/partial thromboplastin time (PTT) or international normalized ratio (INR) within normal range;
• Patients who have had prior treatment with adjuvant immunotherapy are eligible for study randomization provided that therapy ended at least 4 weeks prior to randomization;
• Patients who had prior surgery are eligible if at least 4 weeks have passed since their surgery;
• All toxicities related to prior adjuvant therapy must have resolved and all surgical wounds must have healed;
• Written informed consent and HIPAA authorization obtained from the patient prior to receipt of any study medication or beginning study procedures.

Exclusion

Patients must have none of the following at the time of randomization:

• Pregnancy or nursing;
• Prior therapy for metastatic melanoma including chemotherapy, radiotherapy, hormonal therapy, or biologics;
• Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for treatment of cancer;
• Current or planned participation (from the day of randomization through 30 days after the last dose of MEDI-522) in a research protocol in which an investigational agent or therapy may be administered;
• Received an investigational agent within 4 weeks prior to randomization;
• Known brain metastases or primary brain tumors, ocular melanoma, symptomatic pleural effusion or ascites requiring paracentesis;
• History of prior malignancies within the past 5 years other than non-melanomatous skin cancers that have been controlled, carcinoma in situ of the cervix, T1a or b prostate cancer noted incidentally during a transurethral resection of prostate (TURP) with prostate-specific antigen (PSA) values within normal limits since TURP, or superficial bladder cancer;
• History of pulmonary embolus.
• Any history or evidence of pulmonary embolism or thrombophlebitis (including deep vein thrombosis) requiring anticoagulant therapy (i.e., warfarin or heparin).
• Currently requiring therapeutic anticoagulation.
• Any evidence of hematemesis, melena, hematochezia, or gross hematuria;
• History or presence of bleeding diatheses;
• Elective surgery planned during the study period through 30 days after the last dose of MEDI-522.
• History of hypersensitivity to a previously administered monoclonal antibody.
• History of hypersensitivity to DTIC;
• History of immunodeficiency;
• Known human immunodeficiency virus (HIV) or known active viral hepatic infections;
• A prior myocardial infarction or angina, or uncontrolled/refractory hypertension within 6 months prior to randomization;
• A prior stroke or transient ischemic attack within the past 6 months;
• An active infection requiring systemic antiinfective therapy;
• Prior treatment with MEDI-522 or MEDI-523;
• A general medical or psychological condition or behavior, including substance dependence or abuse that, in the opinion of the investigator, might not permit the patient to complete the study or sign the informed consent.

Arizona
      Mayo Clinic Arizona, Scottsdale,  Arizona,  85259,  United States
California
      Medical Group of North County, Vista,  California,  92083,  United States
      Pacific Shores Medical Group, Long Beach,  California,  90813,  United States
      Saint Francis Memorial Hospital, San Francisco,  California,  94109,  United States
      Cancer Institute Medical Group, Santa Monica,  California,  90404,  United States
Connecticut
      Yale University School of Medicine, New Haven,  Connecticut,  06520,  United States
Florida
      University of Miami, Miami,  Florida,  33136,  United States
Georgia
      Winship Cancer Institute of Emory University, Atlanta,  Georgia,  30322,  United States
Illinois
      Oncology Specialists, S.C., Park Ridge,  Illinois,  60069,  United States
Indiana
      Indiana Oncology Hematology Consultants, Indianapolis,  Indiana,  46202,  United States
      Indiana University Medical Center, Indianapolis,  Indiana,  46202,  United States
Maryland
      Johns Hopkins University - SKCC at Johns Hopkins, Lutherville,  Maryland,  21093,  United States
Massachusetts
      Boston Medical Center, Boston,  Massachusetts,  02118,  United States
Missouri
      Kansas City Oncology & Hematology Group, Kansas City,  Missouri,  64131,  United States
      The Melanoma Center of St. Louis, St. Louis,  Missouri,  63131,  United States
New York
      HemOnc Care, P.C., Brooklyn,  New York,  11235,  United States
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
North Carolina
      UNC-Chapel Hill, Chapel Hill,  North Carolina,  27599,  United States
      Blumenthal Cancer Center, Charlotte,  North Carolina,  28203,  United States
Oregon
      Providence Portland Medical Center, Portland,  Oregon,  97213,  United States
Pennsylvania
      University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15232,  United States
      Thomas Jefferson University, Philadelphia,  Pennsylvania,  19107,  United States
Tennessee
      Vanderbilt University Medical Center, Nashville,  Tennessee,  37232,  United States
Texas
      The University of Texas, MD Anderson Cancer Center, Houston,  Texas,  77030,  United States
      Discovery Alliance, Houston,  Texas,  77030,  United States

Study ID Numbers:  MI-CP095
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  August 5, 2003
ClinicalTrials.gov Identifier:  NCT00066196
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08