MEDI-522 in the Treatment of Patients With Metastatic Androgen-Independent Prostate Cancer

Phase II, Randomized, Open-Label, Two-Arm, Multicenter Study of MEDI-522, a HuMA Directed Against the Human Alpha V Beta 3 Integrin, in Combination With Docetaxel, Prednisone, and Zoledronic Acid in the Treatment of Patients With Metastatic Androgen-Independent Prostate Cancer

The primary objectives of this study are:

1. To explore the antitumor activity of MEDI-522 in combination with docetaxel, prednisone, and zoledronic acid in patients with metastatic Androgen-Independent Prostate Cancer (AIPC); and
2. To summarize the safety of MEDI-522 in combination with docetaxel, prednisone, and zoledronic acid in this patient population.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Biological: MEDI-522; Biological: Docetaxel + Prednisone* + Zoledronic Acid

Detailed Description

This is a Phase II, randomized, open-label, two-arm, multicenter study of MEDI-522 in combination with docetaxel, prednisone, and zoledronic acid in patients with metastatic AIPC.

• Study Type: Interventional
• Enrollment: 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2020
    • A.Z. Middelheim
  • Bruxelles, Belgium, 1070
    • University Hospital Erasme
  • Kortrijk, Belgium, 8500
    • AZ Groeninge
  • Roeselare, Belgium, 8800
    • H.-Hartziekenhuis Medische Onocology-Hematologie
• Canada
  • Montreal, Canada, H2L 4M1
    • Centre Hospitalier de l'Universite de Montreal
• Hungary
  • Miskolc, H, Hungary, 3518
    • Borsod County Teaching Hospital
  • Szolnok, Hungary, 5000
    • Szolnoki Mav Hospital
• Israel
  • Kfar Saba, Israel, 44281
    • Sapir Medical Center - Meir Hospital
  • Petach Tikva, Israel, 49100
    • Rabin Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
• Poland
  • Slupsk, Poland
    • Samodzielny Publiczny Wojewodzki Szpital Zespolony
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Arkhangelsk Regional Oncology Center
  • Chelyabinsk, Russian Federation, 454087
    • Chelyabinsk Regional Oncology Center
  • Kazan, Russian Federation, 420111
    • Kazan City Oncology Center
  • Moscow, Russian Federation, 115478
    • Blokhin Cancer Research Center
  • Moscow, Russian Federation, 129128
    • Semashko Central Clinical Hospital
  • Moscow, Russian Federation, 117387
    • Russian Research Center of Radiology
  • Obninsk, Russian Federation, 249036
    • Medical Rediological Research Centre of Ran
  • Saint Petersburg, Russian Federation, 198255
    • City Clinical Oncology Dispensary
  • Samara, Russian Federation, 443066
    • Samara Regional Oncology Center
  • Voronezh, Russian Federation, 394000
    • Voronezh Regional Oncology Clinical Center
• United States
  • Alabama
    • Hoover, Alabama, United States, 35216
      • Clinical Research Consultants, Inc.
  • Arizona
    • Springdale, Arizona, United States, 72764
      • Highlands Oncology Group, P.A.
    • Tucson, Arizona, United States, 85704
      • Arizona Hematology-Oncology, P.C.
  • California
    • Gilroy, California, United States, 95020-3535
      • South Valley Medical Plaza
    • San Bernardino, California, United States, 92404
      • San Bernardino Urological Associates
    • San Francisco, California, United States, 94109
      • Saint Francis Memorial Hospital
    • Stanford, California, United States, 94305-5826
      • Stanford Advanced Medical Center
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialist
    • Inverness, Florida, United States, 34452
      • The Florida Wellcare Alliance, L.C.
    • Lake Worth, Florida, United States
      • Hemotology/Oncology Associates
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Medical Consultants
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University Of Chicago
    • Harvey, Illinois, United States, 60426
      • Ingalls Hospital
  • Indiana
    • Munster, Indiana, United States, 46321
      • The Community Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Hematology Oncology Services, LLC
  • Minnesota
    • Robbinsdale, Minnesota, United States, 55422
      • Hubert H. Humphrey Cancer Center
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • North Mississippi Hematology & Oncology Associates, Ltd.
  • Missouri
    • St. Louis, Missouri, United States, 63110-1010
      • Washington University School of Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Comprehensive Cancer Center of Nevada
    • Reno, Nevada, United States, 89502
      • VA Sierra Nevada Health Care System
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • New Mexico Oncology Hematology, Consultants Ltd.
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY Down State Medical Center
    • Buffalo, New York, United States, 14215-1199
      • VA Western New York Healthcare System
    • East Setauket, New York, United States, 11733
      • North Shore Hematology Oncology Assoc., PC
    • New York, New York, United States, 10032-3713
      • Columbia Presbyterian Medical Center
    • Northport, New York, United States, 11768
      • VA Medical Center
  • North Carolina
    • Raleigh, North Carolina, United States, 27609
      • Raleigh Hematology Oncology Association
  • North Dakota
    • Bismark, North Dakota, United States
      • Clinical Research Services
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0501
      • University of Cincinnati, Barrett Cancer Center
  • South Carolina
    • Sumter, South Carolina, United States, 29150
      • Santee Hematology/Oncology
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Associates in Oncology and Hematology
    • Knoxville, Tennessee, United States, 37916
      • Thompson Cancer Survival Center
    • Nashville, Tennessee, United States, 37203
      • The Sarah Cannon Cancer Center
  • Virginia
    • Danville, Virginia, United States, 24541-4155
      • Danville Hematology and Oncology
    • Richmond, Virginia, United States, 23230
      • Virginia Cancer Institute
  • Washington
    • Lacey, Washington, United States, 98503
      • Western Washington Oncology, Inc., P.S.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Adult men at least 18 years of age at the time of randomization.

• Metastatic, histologically or cytologically confirmed adenocarcinoma of the prostate that has progressed after start of androgen deprivation therapy, which includes prior orchiectomy or medical castration using leuteinizing hormone-releasing hormone (LHRH) antagonists such as leuprolide or goserelin (patients must remain on LHRH analogue therapy for the duration of the study if not surgically castrated). Progressive disease should be documented by:

  a. PSA progression (defined as two consecutive increases in PSA over a previous reference value, with the first increase in PSA occurring at a minimum of 1 week after the reference value [obtained within 2 months prior to study randomization] and confirmed by a subsequent increase in PSA whose value must be ³ 5 ng/mL prior to study randomization);41 and one of the following: i. Bone metastases (defined as ³3 foci on bone scan and confirmed radiologically within 1 month prior to study randomization); or ii. Measurable non-bony metastatic disease (documented by radiographic studies performed within 1 month prior to study randomization).

• Serum testosterone levels <50 ng/dL documented in non-surgically castrated patients within 21 days prior to randomization.
• Prior treatment with nonsteroidal antiandrogens (e.g., flutamide or bicalutamide) is allowed provided:
• There is evidence of disease progression (defined in Inclusion Criteria #2) following withdrawal of antiandrogens; and b. At least 4 weeks for flutamide or 6 weeks for bicalutamide have passed since last treatment.
• Prior treatment with ketoconazole and/or steroids is allowed provided at least 4 weeks have passed since last treatment. There are no restrictions for use of prednisone (5 mg twice daily) or another functionally equivalent oral corticosteroid for treatment of pain.
• In the rare instance a patient is potent, he must agree to practice an effective method of contraception including condom or abstinence, unless his sexual partner is sterile, from the time of first administration of MEDI-522 or docetaxel through 30 days after the last dose of either docetaxel or MEDI-522, whichever is the last drug discontinued.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 documented within 21 days prior to randomization.
• Life expectancy, in the opinion of the investigator, of at least 6 months.
• White blood cell (WBC) count ≥ 3,000/mm3; absolute neutrophil count (ANC) ≥ 1,500/mm3; platelet count ≥ 100,000/mm3; and hemoglobin ³ 9 g/dL documented within 21 days prior to randomization.
• Bilirubin ≤ ULN; aspartate transaminase (AST)/alanine transaminase (ALT) £1.5 times ULN or if AST/ALT is >1.5 times ULN, then alkaline phosphatase must be £2.5 times ULN; serum creatinine ≤ 1.5 mg/dL; INR within normal range, unless a patient is receiving anticoagulation therapy; and corrected serum calcium between 8.0-11.5 mg/dL documented within 21 days prior to randomization.
• Patients who had prior major surgery are eligible if at least 4 weeks have passed since their surgery and all surgical wounds have healed prior to study randomization.
• Prior radiotherapy including therapeutic isotopes is allowed provided measurable or evaluable disease that is clearly progressing is present and all acute radiation-related toxicities have resolved prior to study randomization.
• Prior treatment with unconventional therapy for malignancy (e.g., vitamins, St. John's Wort, PC-SPES, saw palmetto, or other herbal remedies) is allowed provided at least 4 weeks have passed since last treatment prior to randomization.
• Written informed consent and HIPAA authorization (USA sites only) obtained from the patient prior to receipt of any study medication or beginning study procedures.

Exclusion Criteria:

• Prior chemotherapy for metastatic prostate cancer (prior adjuvant chemotherapy is allowed provided it is non-taxane based and at least 6 months have passed since last treatment).
• Prior treatment with other investigational agents within 4 weeks prior to randomization.
• Planned concurrent treatment with unconventional therapy for malignancy (e.g., vitamins, St. John's Wort, PC-SPES, saw palmetto, or other herbal other herbal remedies) based on medical history. Currently requiring anticoagulation (excluding use of heparin flush solutions for maintenance of catheter lines) for any thromboembolic disease based on medical history and physical examination.
• Current or planned participation (from the time of randomization through 30 days after the last dose of either docetaxel or MEDI-522, whichever is the last drug discontinued) in a research protocol in which an investigational agent or therapy may be administered.
• Any evidence of or history elicited by the investigator of prior treatment with MEDI-522 or MEDI-523.
• Prior treatment with calcitonin, mithramycin, or gallium nitrate within 2 weeks prior to randomization.
• Clinically evident central nervous system (CNS) metastasis.
• History of prior malignancies within the past 5 years other than adequately treated basal cell or squamous cell skin cancer or Stage I or II cancer currently in complete remission;
• Any evidence of or history elicited by the investigator of symptomatic cerebrovascular events (i.e., stroke or transient ischemic attack) within 6 months prior to randomization; or any history or evidence of pulmonary embolism or thrombophlebitis (including deep vein thrombosis) requiring anticoagulant therapy (e.g., warfarin or heparin).
• Any evidence of or history elicited by the investigator of myocardial infarction or angina within 6 months prior to randomization.
• Any evidence of or history elicited by the investigator of hematemesis, melena, hematochezia, or uncontrolled gross hematuria within 4 weeks prior to randomization.
• Any evidence of or history elicited by the investigator of bleeding diatheses.
• Major elective surgery planned from the time of randomization through 30 days after the last dose of either docetaxel or MEDI-522, whichever is the last drug discontinued.
• Any evidence of or history elicited by the investigator of hypersensitivity to a previously administered monoclonal antibody.
• Any evidence of or history elicited by the investigator of hypersensitivity to drugs formulated with polysorbate 80, prednisone (or other functionally equivalent oral corticosteroid), or zoledronic acid.
• Known human immunodeficiency virus (HIV) or known active viral hepatic infections based on medical history and physical examination.
• Any evidence of or history elicited by the investigator of uncontrolled or refractory hypertension or uncontrolled diabetes despite medication within 6 months prior to randomization.
• Any evidence of or history elicited by the investigator of an active infection requiring parenteral anti-infective therapy.
• 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 + Docetaxel + Prednisone + Zoledronic Acid (N=55)	Biological: MEDI-522; IV at a concentration of 50 mg/mL and 10mL vials
Other: 2; Docetaxel + Prednisone + Zoledronic Acid (N=55)	Biological: Docetaxel + Prednisone* + Zoledronic Acid; IV 75 mg/m2 IV 3-4 mg 5 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to disease progression	Baseline to disease progression
PSA Response Rate	Baseline to disease progression
Tumor Response Rate	Baseline to disease progression

Secondary Outcome Measures

Outcome Measure	Time Frame
Anti-bone resorption assessed as the incidence of skeletal related events (SREs). (SREs) are defined as radiotherapy, surgery, pathologic bone fracture, spinal cord fracture. Overall survival will also be measured.	Baseline to disease progression

Collaborators and Investigators

• Sponsor: MedImmune LLC

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: November 12, 2003
• First Submitted That Met QC Criteria: November 14, 2003
• First Posted (Estimate): November 17, 2003

Study Record Updates

• Last Update Posted (Estimate): January 15, 2008
• Last Update Submitted That Met QC Criteria: January 11, 2008
• Last Verified: January 1, 2008

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Bone Density Conservation Agents; Docetaxel; Prednisone; Zoledronic Acid
• Other Study ID Numbers: MI-CP098