Evaluating The Antitumor Activity Of MEDI-522 With Or Without Dacarbazine In Patients With Metastatic Melanoma

A Phase II, Randomized, Open-Label Study Evaluating The Antitumor Activity Of MEDI-522, A Humanized Monoclonal Antibody Directed Against The Human Alpha V Beta 3 Integrin, ± Dacarbazine In Patients With Metastatic Melanoma

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.

Study Overview

• Status: Completed
• Conditions: Melanoma; Malignant Metastatic Melanoma
• Intervention / Treatment: Biological: Integrin + Dacarbazine; Biological: MEDI--522

Detailed Description

This is a Phase II, randomized, open-label, two-arm, multicenter study of MEDI 522 ± DTIC in previously untreated (other than adjuvant immunotherapy) patients with Stage IV metastatic melanoma (AJCC staging).

• Study Type: Interventional
• Enrollment: 110
• Phase: Phase 2

Contacts and Locations

Study Locations

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

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

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.

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
Active Comparator: 1; MEDI-522	Biological: MEDI--522; IV administration supplied in 10 mL vials containing 100 mg of MEDI-522 at a concentration of 10 mg/mL.
Other: 2; Integrin + Dacarbazine	Biological: Integrin + Dacarbazine; supplied in other formulations

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Explore antitumor activity of MEDI-522 in patients with metastatic melanoma.	Screening and after every 2 cycles of treatment until disease progression. At least 4 weeks after a patient demonstrates response.

Secondary Outcome Measures

Outcome Measure	Time Frame
Determine the safety of MEDI-522 and/or DTIC in this patient population.	Every week until disease progression, and 30 days after disease progression.

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Investigators: Study Director: Luz Hammershaimb, M.D., MedImmune LLC

Study record dates

Study Major Dates

• Study Start: August 1, 2003
• Primary Completion (Anticipated): April 1, 2007
• Study Completion (Actual): June 1, 2007

Study Registration Dates

• First Submitted: August 5, 2003
• First Submitted That Met QC Criteria: August 6, 2003
• First Posted (Estimate): August 7, 2003

Study Record Updates

• Last Update Posted (Estimate): January 15, 2008
• Last Update Submitted That Met QC Criteria: January 14, 2008
• Last Verified: January 1, 2008

More Information

Terms related to this study

• 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; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Dacarbazine
• Other Study ID Numbers: MI-CP095