Clinical trial NCT00072930: MEDI-522 in the Treatment of Patients With Metastatic Androgen-Independent Prostate Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2003-11-17
Enrollment: 150
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time to disease progression
timeFrame: Baseline to disease progression
measure: PSA Response Rate
timeFrame: Baseline to disease progression
measure: Tumor Response Rate
timeFrame: Baseline to disease progression
Secondary outcomes:
measure: 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.
timeFrame: Baseline to disease progression
Other outcomes:
Locations:
city: Hoover
country: United States
facility: Clinical Research Consultants, Inc.
state: Alabama
city: Springdale
country: United States
facility: Highlands Oncology Group, P.A.
state: Arizona
city: Tucson
country: United States
facility: Arizona Hematology-Oncology, P.C.
state: Arizona
city: Gilroy
country: United States
facility: South Valley Medical Plaza
state: California
city: San Bernardino
country: United States
facility: San Bernardino Urological Associates
state: California
city: San Francisco
country: United States
facility: Saint Francis Memorial Hospital
state: California
city: Stanford
country: United States
facility: Stanford Advanced Medical Center
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialist
state: Florida
city: Inverness
country: United States
facility: The Florida Wellcare Alliance, L.C.
state: Florida
city: Lake Worth
country: United States
facility: Hemotology/Oncology Associates
state: Florida
city: Honolulu
country: United States
facility: Hawaii Medical Consultants
state: Hawaii
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Harvey
country: United States
facility: Ingalls Hospital
state: Illinois
city: Munster
country: United States
facility: The Community Hospital
state: Indiana
city: New Orleans
country: United States
facility: Hematology Oncology Services, LLC
state: Louisiana
city: Robbinsdale
country: United States
facility: Hubert H. Humphrey Cancer Center
state: Minnesota
city: Tupelo
country: United States
facility: North Mississippi Hematology & Oncology Associates, Ltd.
state: Mississippi
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Center of Nevada
state: Nevada
city: Reno
country: United States
facility: VA Sierra Nevada Health Care System
state: Nevada
city: Albuquerque
country: United States
facility: New Mexico Oncology Hematology, Consultants Ltd.
state: New Mexico
city: Brooklyn
country: United States
facility: SUNY Down State Medical Center
state: New York
city: Buffalo
country: United States
facility: VA Western New York Healthcare System
state: New York
city: East Setauket
country: United States
facility: North Shore Hematology Oncology Assoc., PC
state: New York
city: New York
country: United States
facility: Columbia Presbyterian Medical Center
state: New York
city: Northport
country: United States
facility: VA Medical Center
state: New York
city: Raleigh
country: United States
facility: Raleigh Hematology Oncology Association
state: North Carolina
city: Bismark
country: United States
facility: Clinical Research Services
state: North Dakota
city: Cincinnati
country: United States
facility: University of Cincinnati, Barrett Cancer Center
state: Ohio
city: Sumter
country: United States
facility: Santee Hematology/Oncology
state: South Carolina
city: Chattanooga
country: United States
facility: Associates in Oncology and Hematology
state: Tennessee
city: Knoxville
country: United States
facility: Thompson Cancer Survival Center
state: Tennessee
city: Nashville
country: United States
facility: The Sarah Cannon Cancer Center
state: Tennessee
city: Danville
country: United States
facility: Danville Hematology and Oncology
state: Virginia
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Lacey
country: United States
facility: Western Washington Oncology, Inc., P.S.
state: Washington
city: Antwerpen
country: Belgium
facility: A.Z. Middelheim
city: Bruxelles
country: Belgium
facility: University Hospital Erasme
city: Kortrijk
country: Belgium
facility: Az Groeninge
city: Roeselare
country: Belgium
facility: H.-Hartziekenhuis Medische Onocology-Hematologie
city: Montreal
country: Canada
facility: Centre Hospitalier de L'Universite de Montreal
city: Miskolc, H
country: Hungary
facility: Borsod County Teaching Hospital
city: Szolnok
country: Hungary
facility: Szolnoki Mav Hospital
city: Kfar Saba
country: Israel
facility: Sapir Medical Center - Meir Hospital
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Slupsk
country: Poland
facility: Samodzielny Publiczny Wojewodzki Szpital Zespolony
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Oncology Center
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Oncology Center
city: Kazan
country: Russian Federation
facility: Kazan City Oncology Center
city: Moscow
country: Russian Federation
facility: Blokhin Cancer Research Center
city: Moscow
country: Russian Federation
facility: Russian Research Center of Radiology
city: Moscow
country: Russian Federation
facility: Semashko Central Clinical Hospital
city: Obninsk
country: Russian Federation
facility: Medical Rediological Research Centre of Ran
city: Saint Petersburg
country: Russian Federation
facility: City Clinical Oncology Dispensary
city: Samara
country: Russian Federation
facility: Samara Regional Oncology Center
city: Voronezh
country: Russian Federation
facility: Voronezh Regional Oncology Clinical Center
Study officials:
affiliation: MedImmune LLC
name: Luz Hammershaimb, MD
role: STUDY_DIRECTOR
References: